Use of combined oral contraceptives among women with migraine and nonmigrainous headaches: a systematic review

Herbert B Peterson

National Center for Chronic Disease Prevention and Health Promotion

Abstract: This systematic review examines evidence evaluating whether women with headaches who use combined oral contraceptives (COCs) have a greater risk of stroke than women with headaches who do not use COCs. We searched MEDLINE for articles published from 1966 through March 2005 relevant to headaches and COC use as risk factors for stroke. Of the 79 articles identified, nine met our selection criteria (eight reports of six observational studies plus one meta-analysis). All studies reported specifically on migraine headaches. Evidence from six case-control studies suggested that COC users with a history of migraine were two to four times as likely to have an ischemic stroke as nonusers with a history of migraine. The odds ratios for ischemic stroke ranged from 6 to almost 14 for COC users with migraine compared with nonusers without migraine. The three studies that provided evidence on hemorrhagic stroke reported low or no risk associated with migraine or with COC use.


Estrogen carcinogenesis in breast cancer

Nancy E Davidson

Sidney Kimmel Comprehensive Cancer Center

Abstract: Estrogen exposure is a major determinant of the risk of breast cancer. This article reviews how genotoxic, mutagenic metabolites of estrogen and stimulation of tissue growth by the hormone participate in the pathogenesis of breast cancer.


DIR Jahrbuch 2005 (Deutsches IVF-Register Annual Report 2005)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2005. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


The Present State of NFP Science

The Present State of NFP Science


Acceptability of a home monitor used to aid in conception: psychosocial factors  and couple dynamics

Abstract:
Background: Assessing the psychological acceptability of technologies designed to assist couples in achieving pregnancy is complex.

Objective: The current study developed measures relating to the impact of one such technology on 52 couples' relationships, their feelings relating to pregnancy status and their feelings about the technology itself.

Methods: Pregnancy status and daily logs of sexual activity were recorded for four menstrual cycles, in addition to the completion of acceptability questionnaires.

Results: Baseline acceptability measures were more favorable among couples eventually achieving pregnancy. For couples not becoming pregnant, acceptability declined over time and relationships became more strained. Behavioral data clearly indicated a "targeting" and focusing of sexual activity in response to the information displayed by the monitor.

Conclusion: Expectations of success, couple disagreements about prior failure and partner communication patterns appear to be related to pregnancy success when using such technology.


Effects of TeenSTAR, an abstinence only sexual education program, on adolescent  sexual behavior

Rosa Riquelme R

Pontificia Universidad Católica de Chile

Abstract:
Background: Urgent measures are required to stop the increase in the frequency of pregnancies and sexually transmitted diseases among teenagers. A means of facing this problem is promoting sexual abstinence among youngsters. There are studies that confirm the efficacy of this approach.

Aim: To show the results of the application of a holistic sexuality program (TeenSTAR) among Chilean teenagers. SUBJECTS AND

Methods: Students attending basic or high school were divided into a control or study group. The control group (342 students) received the usual education on sexuality given by their schools and the study group (398 students) participated in twelve TeenSTAR sessions lasting 1.5 hours each, given by a trained professor. Assessment of achievements was made using an anonymous questionnaire answered at the start and end of the program.

Results: The rates of sexual initiation among control and study groups were 15 and 6.5%, respectively. Among sexually active students, 20% of those in the study group and 9% of those in the control group discontinued sexual activity.

Conclusions: A higher proportion of students in the TeenSTAR program retarded their sexual initiation or discontinued sexual activity and found more reasons to maintain sexual abstinence than control students.


Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus apella)

Abstract: The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.


Depression associated with combined oral contraceptives--a pilot study

Abstract: Although there have been numerous studies investigating the relationship between the use of oral contraceptives and depressive symptoms, they have differed widely in both their methods and findings. A particular problem is determining and quantifying depression. The authors onducted a pilot study using well validated depression rating scales. (non-author abstract)


Molecular aspects of declining sperm motility in older men

Abstract:
OBJECTIVE: To investigate the molecular mechanism for declining sperm motility in older men.

DESIGN: Retrospective and prospective study.

SETTING: University-based andrology unit.

PATIENT(S): Semen was collected from 2,111 patients and sperm donors.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Age, sperm concentration, ejaculate volume, sperm motility (including velocity average path, velocity straight line, velocity curvilinear, linearity, and lateral head displacement), normal sperm morphology, percentage of abnormally blue-stained flagella, and total and free T, FSH, and LH concentrations were analyzed. In addition, the zinc concentration in the seminal fluid, flagella, and the whole spermatozoa was measured by means of atomic absorption spectrometry.

RESULT(S): Patient age correlated negatively with T concentration and sperm motility, including velocity, but positively with the percentage of abnormally stained flagella and the flagellar zinc. Whereas the percentage of abnormally stained flagella correlated negatively with motility and sperm velocity, there was a positive relationship with the flagellar zinc content. Flagellar zinc content was negatively correlated with motility. Testosterone showed a positive relationship with motility and sperm concentration.

CONCLUSION(S): Because the epididymis is functionally T-dependent, our data suggest that the removal of zinc from the outer dense fibers during epididymal sperm maturation is affected in aging men, which in turn will result in decreased sperm motility.


Meta-analysis of cancer incidence in children born after assisted reproductive technologies

Abstract: A meta-analysis was performed on 11 cohort studies of Assisted Reproductive Technologies (ART) and subsequent childhood cancer, published up to February 2005, which reported comparable, nonoverlapping data, and then restricted to eight studies which presented a similar research design. The overall Standardised Incidence Ratio was 1.33 (95% CI 0.62-2.85), and 0.77 (95% CI 0.41-1.42) when the analysis was restricted to eight studies. No evidence of publication bias was observed for the overall analysis. The data are consistent with a lack of increase in risk of childhood cancer, though the amount of data on ART and cancer is still limited; larger multicentric studies as well as a pooled analysis on the available data are warranted.


In vivo and in vitro estrogenic and progestagenic actions of Tibolone

Marsha M Pinto

Osteoporosis Program, University Health Network, Toronto, ON M5G 2C4, Canada. marshapinto@gmail.com.

Abstract: Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STATS, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.


The influence of smoking and other cofactors on the time to onset to cervical cancer in a southern European population

A Matos

Molecular Oncology Unit and Gynaecology Department, Instituto Português de Oncologia, Porto 4200-072, Portugal.

Abstract: Cervical cancer is a complex and multifactorial disease. Although there are substantial data supporting the causative role of persistent human papillomavirus (HPV) infection in the development of cervical cancer, the complete course of the disease has never been completely understood. Several risk cofactors have been suggested with controversial results. Portugal has the highest incidence of squamous cell carcinoma (SCC) within western Europe and there are no known studies regarding the role of cofactors in SCC. The aim of our study was to evaluate the role of smoking, sexual behaviour, reproductive and contraceptive history, in the time-to-onset (TTO) of severe cervical lesions (HGSIL/SCC) in the Portuguese population. We verified that age of first sexual intercourse under 18 years (odds ratio (OR) 2.8), pregnancy (OR 2.9), first pregnancy under 21 years (2.6), number of pregnancies (OR 2.3-5.4) and parity (OR 1.9-5.7) are risk factors in the development of cervical neoplasia. Smoke exposure index (SEI) was significantly different (P=0.002) between cases and controls. Our results regarding time-to-onset demonstrate that smoking (P<0.001, log rank test), number of sexual partners (P<0.001, log rank test) and use of oral contraceptives (P<0.001, log rank test) are important determinants in the earlier onset of severe cervical lesions. Using this approach, our findings may help to clarify the role of smoking and other cofactors in the persistence and progression of cervical lesions.


Oral contraceptive use and risk of breast cancer among women with a family  history of breast cancer: a prospective cohort study

Abstract: Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large cohort study in Canada. The cohort consisted of the 27,318 women in the Canadian National Breast Screening Study who reported a family history of breast cancer on enrollment into the study. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000, depending upon the province. During a mean of 16.0 years of follow-up, we observed 1707 incident cases of breast cancer among women with any history of breast cancer of which 795 cases occurred among women with a mother, sister, and/or daughter with breast cancer. Among women with any family history of breast cancer, ever use of oral contraceptives was associated with a 12% reduction in risk of breast cancer (95% confidence interval [CI]=0.73-1.07), and there was an inverse trend with increasing duration of use of borderline statistical significance (p(trend)=0.03). Although we also observed a 25% lower risk of breast cancer associated with oral contraceptive use of greater than 84 months versus never use among women with a first degree relative with breast cancer, this finding was not statistically significant (95% CI=0.47-1.19, p(trend)=0.48). Our data raise the possibility that relatively long duration of oral contraceptive use may be inversely associated with risk among women with a family history of breast cancer.


Protocol for determining fertility while breastfeeding and not in cycles

Abstract: A protocol was developed and evaluated for nonovulating breastfeeding women to determine potential fertility with an electronic hormonal fertility monitor. The amount of required abstinence (i.e., days of potential fertility) through the first menstrual cycle indicated by the fertility monitor was significantly lower (17% of the total days) compared with the amount of abstinence (50% of the total days) indicated by the self-observation of cervical mucus.


Recent use of oral contraceptives and the risk of multiple sclerosis

Susan S Jick

Boston Collaborative Drug Surveillance Program

Abstract:
Background: Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS).

Objective: To examine whether recent oral contraceptive use and pregnancy history are associated with the risk of MS. DESIGN AND Setting: A case-control study nested in the General Practice Research Database. This database contains prospective health information (drug prescriptions and clinical diagnoses) on more than 3 million Britons who are enrolled with selected general practitioners.

Participants: One hundred six female incident cases of MS, younger than 50 years, with at least 3 years of continuous recording in the General Practice Research Database before the date of first symptoms (index date), identified between January 1, 1993, and December 31, 2000, and 1001 controls matched on age, practice, and date of joining the practice. Main Outcome Measure Incidence of first symptoms of MS, confirmed through medical records.

Results: The incidence of MS was 40% lower (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) in oral contraceptive users compared with nonusers during the previous 3 years. The risk of MS increased in the 6 months after pregnancy (odds ratio, 2.9, 95% confidence interval, 1.2-6.6), but it was not otherwise related to parity.

Conclusions: The hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of MS, and the postpartum period may be associated with a short-term increase in the risk of MS.


Basal body temperature assessment: is it useful to couples seeking pregnancy?

Abstract: Advanced practice nurses in primary care settings are often asked to give appropriate advice to couples seeking pregnancy. This article examines the issue of basal body temperature (BBT), a time-honored way to establish the presence of ovulatory cycles, and asks if BBT is an outdated recommendation. The article also reviews the benefits and limitations of recommending BBT to couples seeking pregnancy in light of recent fecundity research.

MCN. The American journal of maternal child nursing


Impact of teenage oral contraceptive use in a population-based series of  early-onset breast cancer cases who have undergone BRCA mutation testing

Abstract: Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.

European Journal of Cancer (Oxford, England : 1990)


Health-related quality of life measurements in elderly Canadians with osteoporosis compared to other chronic medical conditions: a population-based study from the Canadian Multicentre Osteoporosis Study (CaMos)

Alexandra Papaioannou

McMaster University, Hamilton, ON, Canada

Abstract: The objective of this research was to determine the relative decrement in health-related quality of life, as measured by the health utilities index mark 3 (HUI3), in osteoporosis compared to other chronic medical conditions. The impact of chronic medical conditions other than osteoporosis on HUI3 measurements had been previously established in the 1996/1997 Canadian National Population Health Survey (NPHS). The Canadian Multicentre Osteoporosis Study (CaMos) is a national population-based study in which regional participants were randomly recruited, regardless of presence of osteoporosis. We analyzed data from participants aged > or = 65 years who completed a baseline HUI3 questionnaire and provided information on their medical history (n=3,750). We determined the ageand gender-adjusted mean decrement in HUI3 for several chronic medical conditions, including osteoporosis. The mean changes in HUI3 adjusted for age and gender (with 95% confidence intervals) were as follows: arthritis -0.10 (-0.11, -0.09), chronic obstructive pulmonary disease (COPD) -0.07 (-0.09, -0.05), diabetes mellitus -0.05 (-0.08, -0.03), heart disease -0.06 (-0.08, -0.04), hypertension -0.02 (-0.03, -0.01), and osteoporosis -0.08 (-0.11, -0.06), respectively (model r2=0.17; P<0.0001). These findings were comparable to those observed in the NPHS, with the exception of osteoporosis, which had not been previously studied in this fashion. The decrement in HUI3 score seen in participants with osteoporosis was comparable to that observed in other chronic medical conditions, such as arthritis, COPD, diabetes mellitus or heart disease.


Risk factors for inflammatory bowel disease in the general population

L. A. García Rodríguez

Centro Español de Investigación Farmacoepidemiológica

Abstract:
Background: The aetiology of inflammatory bowel disease remains largely unknown.

Aim: We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease.

Methods: We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls.

Results: Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00).

Conclusions: Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.


Prior oral contraception and postmenopausal fracture: a Women's Health Initiative  observational cohort study

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract:
Objective: To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause.
Design: A prospective cohort of 93,725 postmenopausal women.
Setting: Forty Women's Health Initiative (WHI) clinical centers across the United States. PATIENT(S): Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire. RESULT(S): The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women without any postmenopausal hormone treatment, past OC use for < or =5 years led to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97-1.23) compared with never users. CONCLUSION(S): This study does not support the idea that past OC use protects against later fracture.


Ovarian aging and the perimenopausal transition: the paradox of endogenous  ovarian hyperstimulation

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: The purpose of this review is to put into a useful clinical context the changing over time of basic ovarian-pituitary-hypothalamic relationships during perimenopause. "Perimenopause" means changes in ovarian hormones, feedback relationships, and clinical experiences beginning in women ages 35-50 with regular flow and ending 1 yr after the final menstrual flow. A key observation must be explained--estradiol levels are increased in perimenopause. Inhibin B levels are lower and activin may be higher in midlife, menstruating women. These changes probably cause higher follicular phase FSH levels--"endogenous ovarian hyperstimulation" results. The positive estradiol feedback on LH is also disturbed--midcycle LH peaks and mid-luteal slow-frequency, high-amplitude LH pulses are less frequent. In addition to higher levels, estradiol receptors may increase in tissues of symptomatic women. Despite hyperstimulation of follicles, progesterone levels and luteal phase lengths are paradoxically decreased--reasons probably include LH peak disruptions and estrogen-stimulated greater corticotrophin-mediated reproductive suppression. In summary, disturbed feedback relationships causing higher and unpredictable estrogen and lower progesterone levels occur throughout perimenopause, especially during regular cycles. Prospective, population-based research is needed to systematically relate these feedback hormonal changes to clinical characteristics and to allow a diagnosis of perimenopause in regularly cycling midlife women.


Determination of the fertile window: reproductive competence of women--European  cycle databases

Petra Frank-Herrmann

Department of Gynaecological Endocrinology and Fertility Disorders, University of Heidelberg, Vossstrasse 9, 69115 Heidelberg, Germany. petra.frank-herrmann@med.uni-heidelberg.de

Abstract:
Objectives: The objective of the present paper is to review the main results of recent European cycle databases on ovulation detection and determination of the fertile window performed by the women themselves.

Methods: The ongoing German Long-term Cycle Database currently comprises 32788 prospectively collected cycle charts of 1551 women, the I European Cycle Database (10 countries) 1328 women/19048 cycles, the II European Cycle Database (six countries) 782 women/6724 cycles, and the World Health Organization Database (one European country) 234 women/2808 cycles. The women record cycle parameters (cervical mucus changes, temperature rise, etc.), family planning intention and sexual behavior.

Results: With the symptothermal method of natural family planning it has become possible to determine the fertile window in order to avoid pregnancy with a method effectiveness of 0.3%. According to a small sub-study, the ovulation time observed by the women themselves correlates closely with ovulation detected by ultrasound and measurement of luteinizing hormone (correlation within 1 day in 89% of the 62 cycles). Fertility awareness methods can be integrated into the management of sub-fertility. They seem to shorten the time to pregnancy.

Conclusions: Self-observation of the fertile window puts women into a position to develop a high level of reproductive competence that could be used much more in different areas than is currently the case.

Gynecological Endocrinology : the Official Journal of the International Society  of Gynecological Endocrinology


Ultrastructure of the human periovulatory cervical mucus

Francisco Ceric

Pontificia Universidad Católica de Chile

Abstract: Two main types of cervical mucus have been described during the menstrual cycle: oestrogenic and progestative. Each category shows diverse morphological and functional features from the reproductive point of view. Traditionally, this change has been approached by analysing morphological patterns. In fact, a mesh model has been described for cervical mucus, structurally composed of fibrillar subunits with a parallel orientation, together with another model in a characteristic network shape with canalicular units, but the real model is not clear. The objective of our work was to study the different morphological structures of the mucus, as related to the day of follicular rupture (considered as day 0) determined by ultrasound. Cervical mucus samples were obtained from the cervical canal with an ASPIRETTEtrade mark from day -4 to day +1 of the menstrual cycle. Samples were fixed and dried by critical point. The ultrastructure was examined with scanning electron microscopy. The presence of three types of oestrogenic and one type of progestative cervical mucus was confirmed in this period. Our paper shows different types of ultrastructure in the oestrogenic mucus in relation to ovulation, which would help to understand the interaction between male gametes and cervical mucus in migration through the female genital tract.


A review of the multiple actions of melatonin on the immune system

Abstract: This review summarizes the numerous observations published in recent years which have shown that one of the most significant of melatonin's pleiotropic effects is the regulation of the immune system. The overview summarizes the immune effects of pinealectomy and the association between rhythmic melatonin production and adjustments in the immune system as markers of melatonin's immunomodulatory actions. The effects of both in vivo and in vitromelatonin administration on non-specific, humoral, and cellular immune responses as well as on cellular proliferation and immune mediator production are presented. One of the main features that distinguishes melatonin from the classical hormones is its synthesis by a number of non-endocrine extrapineal organs, including the immune system. Herein, we summarize the presence of immune system-synthesized melatonin, its direct immunomodulatory effects on cytokine production, and its masking effects on exogenous melatonin action. The mechanisms of action of melatonin in the immune system are also discussed, focusing attention on the presence of membrane and nuclear receptors and the characterization of several physiological roles mediated by some receptor analogs in immune cells. The review focuses on melatonin's actions in several immune pathologies including infection, inflammation, and autoimmunity together with the relation between melatonin, immunity, and cancer.


The association of hysterectomy and menopause: a prospective cohort study

Abstract:
OBJECTIVE: To determine whether or not hysterectomy leads to an earlier onset of the menopause.

DESIGN: A prospective cohort study.

SETTING: Gynaecology service of large urban hospital.

POPULATION: Premenopausal women with and without hysterectomy.

METHODS: Multivariate survival analysis techniques were used to adjust for differences in initial follicle stimulating hormone (FSH) levels, body mass index, smoking and unilateral oophorectomy between the groups.

MAIN OUTCOME MEASURES: FSH levels were measured for five years following hysterectomy and compared with the comparison group. Menopause was defined as a single FSH measurement of at least 40 IU/L.

RESULTS: Two hundred and fifty-seven women undergoing hysterectomy were compared with 259 women who had not undergone a hysterectomy. Fifty-three women (20.6%) in the hysterectomy group and 19 women (7.3%) in the comparison group reached menopause over the five years of the study. Women in the hysterectomy group with a pre-operative FSH <10 IU/L reached menopause 3.7 years (95% CI 1.5-6.0 years) earlier than women in the comparison group independent of BMI, smoking and unilateral oophorectomy. Twenty-eight women in the hysterectomy group had unilateral oophorectomy and 10 (35.7%) of these women reached menopause over the five years of follow up. Women in the hysterectomy group with unilateral oophorectomy reached menopause 4.4 years (95% CI 0.6, 7.9 years) earlier than women with both ovaries in the hysterectomy group independent of baseline FSH, BMI and smoking.

CONCLUSIONS: Hysterectomy is associated with an earlier onset of menopause. Hysterectomy with unilateral oophorectomy is associated with an even earlier onset of the menopause in this study.

BJOG : an international journal of obstetrics and gynaecology


An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin  therapy for women with clomiphene citrate-resistant polycystic ovarian syndrome

Abstract:
PURPOSE OF Review: Women with polycystic ovarian syndrome are typically anovulatory and require ovulation induction. Ovarian wedge resection was the first treatment for anovulation but was eventually abandoned because of the increased risk of postsurgical adhesions and as medical ovulation induction with clomiphene and gonadotrophins was introduced. However, with the advent of laparoscopy, there has been a return to surgical approaches. The potential advantages of laparoscopic surgery include avoidance of hyperstimulation and the lowered costs make ovarian surgery an attractive alternative to gonadotrophins.
Recent Findings: Clinical trials in New Zealand and the Netherlands have compared costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of treatment in the Netherlands study for the ovarian drilling group was euro 4664 and for the gonadotrophins group was euro 5418. Without the cost of monitoring and the diagnostic laparoscopy then the difference was euro 2110 in favour of ovarian drilling. It was estimated that the cost per term pregnancy would be euro 14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The higher rates of multiple pregnancy in the gonadotrophin group were considered to be responsible for the increased costs. In the New Zealand trial the costs of a live birth were one-third lower in the group that underwent laparoscopic ovarian diathermy compared with those women who received gonadotrophins (NZ$19,640 and 29,836, respectively).
Summary: Treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in reduced direct and indirect costs. The reduction in multiple pregnancies makes the alternative of surgery particularly attractive.

Current Opinion in Obstetrics & Gynecology


A new method for estimating the effectiveness of emergency contraception that accounts for variation in timing of ovulation and previous cycle length

Abstract:
OBJECTIVE: To develop a new method for estimating the effectiveness of emergency contraception (EC) by using information about previous menstrual cycle length, accounting for the variation in the day of ovulation within the menstrual cycle, and comparing the validity of the new and previous methods.

METHOD(S): Secondary analysis of a data set with a biological marker of ovulation and its distribution in the cycle. Based on a sample of cycles with known length and a known biological marker of ovulation, we simulated trials of predetermined EC effectiveness and then calculated estimates of EC effectiveness based on old and new methods.

RESULT(S): Under some conditions, all methods produced biased estimates of effectiveness with simulated trials, especially when the actual effectiveness was low. The systematic bias was minimized with the new method. The new method was robust with regard to the distribution of the day of intercourse in women presenting for EC.

CONCLUSION(S): Future studies of EC effectiveness should consider both the uncertainty in predicting the day of ovulation and previous cycle length. Our estimates of daily fecundity should be replicated with other data sets.


Over-the-counter progesterone cream produces significant drug exposure compared to a food and drug administration-approved oral progesterone product

Abstract: Progesterone products are available in prescription form as well as over-the-counter (OTC) topical preparations sold for "cosmetic" uses. In a randomized study design, the authors compared the drug exposure from an OTC progesterone cream to a Food and Drug Administration-approved oral preparation at the labeled daily doses recommended for each product. Twelve healthy postmenopausal women received 200-mg oral progesterone capsules once daily for 12 days or progesterone cream 40 mg twice daily for 12 days. At steady state (day 12 of each phase), whole-blood samples were collected over 24 hours (oral progesterone) or 12 hours (topical progesterone) and assayed for total progesterone concentration. No significant differences were found in dose-normalized 24-hour progesterone exposure comparing the cream to oral capsules (median AUC(0-24) 12.5 ng x h/mL vs 10.5 ng x h/mL, respectively; P = .81). In light of the potential risks associated with long-term progesterone use, the authors question whether topical progesterone products should be available OTC.


Lepidium meyenii (Maca) increases litter size in normal adult female mice

Abstract:
BACKGROUND: Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age.

METHODS: Adult female Balb/C mice were divided at random into three main groups: i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment.

RESULTS: Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group.

CONCLUSION: Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility.

Reproductive biology and endocrinology : RB&E


Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant

Abstract:
BACKGROUND: A range of treatments have been proposed to improve pregnancy outcome in recurrent pregnancy loss associated with antiphospholipid antibody (APL). Small studies have not resolved uncertainty about benefits and risks.

OBJECTIVES: To examine outcomes of all treatments given to maintain pregnancy in women with prior miscarriage and APL.

SEARCH STRATEGY: We searched the Pregnancy and Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1988 to June 2003), Lupus (volume one to eight, 1991 to 1999) and conference proceedings from the International Symposium on APL up to 1999.

SELECTION CRITERIA: Randomised or quasi-randomised, controlled trials of interventions in pregnant women with a history of pregnancy loss and APL.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed quality and extracted data for studies up to December 1999. One review author performed this for studies after 1999.

MAIN RESULTS: Thirteen studies were found (849 participants). The quality was not high; 50% had clear evidence of allocation concealment. Participant characteristics varied between trials. Unfractionated heparin combined with aspirin (two trials; n = 140) significantly reduced pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with aspirin compared to aspirin (one trial; n = 98) did not significantly reduce pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high-dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR 1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286) resulted in a significant increase in prematurity when compared to placebo, aspirin, and heparin combined with aspirin, and an increase in gestational diabetes, but no significant benefit. Intravenous immunoglobulin +/- unfractionated heparin and aspirin (two trials; n = 58) was associated with an increased risk of pregnancy loss or premature birth when compared to unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to 4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one trial; n = 82) was not significantly different in outcomes.

AUTHORS' CONCLUSIONS: Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.

The Cochrane database of systematic reviews


Changes in pulmonary transfer factor with menstrual cycle phase

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: To determine whether lung transfer factor for carbon monoxide (T(L(CO))) alters during menstrual phase and if steroid hormone levels relate to these changes, T(L(CO)) and T(L(CO)) adjusted for both alveolar volume (T(L)/V(A)) and haemoglobin concentration, were measured at five predefined and hormonally confirmed menstrual phases in 13 women. No difference between phases was observed in T(L(CO)) or adjusted values. Moreover, there was no association between the maximal change in oestradiol, progesterone, or oestradiol:progesterone ratio and the change in T(L(CO)) measured at the same time. When the first five chronological measurements, regardless of the menstrual phase at which they were measured, were analysed, T(L(CO)) changed significantly (p<0.05) with a maximal change between the first and fourth test (-2.69+/-2.53, 95% confidence interval). Although these results indicate that the first in a series of T(L(CO)) measurements may be higher, we found neither menstrual cycle phase nor ovarian hormone-related changes in T(L(CO)), and conclude that its adjustment for menstrual phase may not be necessary.


Effect of environmental tobacco smoke on levels of urinary hormone markers

Xiaojun Xu

Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA

Abstract: Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.


Female reproductive cycle and obsessive-compulsive disorder

Abstract:
BACKGROUND: The aim of our study was to assess whether there is a relationship between reproductive cycle events and the initiation or changes in symptoms of obsessive-compulsive disorder (OCD).

METHOD: Forty-six female outpatients meeting DSM-IV criteria for OCD completed a semistructured interview at our OCD unit to assess the relationship between reproductive cycle events and OCD. Dates of data collection were from January 2001 to December 2003.

RESULTS: In our sample, OCD onset occurred in the same year as menarche in 22% (N = 10), at pregnancy in 2% (N = 1), at postpartum in 7% (N = 3), and at menopause in 2% (N = 1). Worsening of preexisting OCD was reported by 20% of patients (9/45) at premenstruum, 8% (1/12) at pregnancy, 50% (6/12) at postpartum, and 8% (1/12) at menopause. The number of premenstrual mood symptoms, which included anxiety, irritability, mood lability and depressed mood, was associated with both premenstrual worsening of OCD (OR = 5.1, p < .01) and onset or worsening of OCD at postpartum (OR = 2.7, p < .05). Patients with an onset or worsening of OCD at postpartum also more frequently reported pre-menstrual worsening of OCD and previous history of major depressive disorder, including postpartum depression (p < or =.05 for all).

CONCLUSION: In a substantial number of patients, the onset or worsening of OCD was related to reproductive cycle events, especially at menarche and postpartum. Certain women with OCD seem to be vulnerable to worsening of OCD at different reproductive periods that imply hormonal fluctuations, and premenstruum and post-partum were the 2 reproductive events with a greater vulnerability. Those patients whose OCD symptoms appeared to be related to reproductive events also exhibited a greater history of mood symptoms (premenstrual depression and major depressive episodes).


Oral contraceptive use and risk of early-onset breast cancer in carriers and  noncarriers of BRCA1 and BRCA2 mutations

Margaret R E McCredie

University of Otago, Dunedin, New Zealand;

Alice S Whittemore

Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California;

Dee W West

Cancer Prevention Institute of California

Abstract:
Background: Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear.

Methods: Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls.

Results: After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001).

Conclusions: There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American  Association for Cancer Research, Cosponsored by the American Society of  Preventive Oncology


Adolescent pregnancy prevention: An abstinence-centered randomized controlled  intervention in a Chilean public high school

Pilar Vigil

Pontificia Universidad Católica de Chile

Iván Rojas

Universidad Nacional de Córdoba Facultad de Ciencias Químicas

Abstract:
Purpose: To evaluate the efficacy of an abstinence-centered sex education program in adolescent pregnancy prevention, the TeenSTAR Program was applied in a high school in Santiago, Chile.

Methods: A total of 1259 girls from a Santiago high school were divided into three cohorts depending on the year they started high school: the 1996 cohort of 425 students, which received no intervention; the 1997 cohort, in which 210 students received an intervention and 213 (control group) did not; and the 1998 cohort, in which 328 students received an intervention and 83 (control group) did not. Students were randomly assigned to control and intervention groups in these cohorts, before starting with the program. We conducted a prospective, randomized study using the application of the TeenSTAR sex education program during the first year of high school to the intervention groups in the 1997 and 1998 cohorts. All cohorts were followed up for 4 years; pregnancy rates were recorded and subsequently contrasted in the intervention and control groups. Pregnancy rates were measured and Risk Ratio with 95% confidence interval were calculated for intervention and control groups in each cohort.

Results: Pregnancy rates for the intervention and control groups in the 1997 cohort were 3.3% and 18.9%, respectively (RR: 0.176, CI: 0.076-0.408). Pregnancy rates for the intervention and control groups in the 1998 cohort were 4.4% and 22.6%, respectively (RR 0.195, CI: 0.099-0.384).

Conclusions: The abstinence-centered TeenSTAR sex education intervention was effective in the prevention of unintended adolescent pregnancy.

The Journal of Adolescent Health : Official Publication of the Society for  Adolescent Medicine


Taking a basal follicle-stimulating hormone history is essential before  initiating in vitro fertilization

Abstract:
Objective: To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population.
Design: Retrospective clinical study.
Setting: University hospital. PATIENT(S): General IVF patient population. INTERVENTION(S): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. RESULT(S): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. CONCLUSION(S): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates.


New low- and high-tech calendar methods of family planning

Abstract: Calendar-based methods are not usually considered effective or useful methods of family planning among health professionals. However, new "high-" and "low"-tech calendar methods have been developed, which are easy to teach, to use, and may be useful in helping couples avoid pregnancy. The low-tech models are based on a fixed-day calendar system. The high-tech models are based on monitoring urinary metabolites of female reproductive hormones. Both systems have high levels of satisfaction. This article describes these new models of family planning and the research on their effectiveness. The author proposes a new algorithm for determining the fertile phase of the menstrual cycle for either achieving or avoiding pregnancy.


Use of contraception and use of family planning services in the United States:  1982-2002

Abstract:
Objective: This report presents national estimates of contraceptive use and method choice based on the 1982, 1995, and 2002 National Surveys of Family Growth (NSFG). It also presents data on where women obtained family planning and medical services, and some of the services that they received.

Methods: Data were collected through in-person interviews with 12,571 men and women 15-44 years of age in the civilian noninstitutional population of the United States in 2002. This report is based on the sample of 7,643 women interviewed in 2002. The response rate for women in the study was about 80 percent.

Results: The leading method of contraception in the United States in 2002 was the oral contraceptive pill, used by 11.6 million women; the second leading method was female sterilization, used by 10.3 million women. The condom was the third-leading method, used by about 9 million women and their partners. The condom is the leading method at first intercourse; the pill is the leading method among women under 30; and female sterilization is the leading method among women 35 and older. More than 98 percent of women 15-44 years of age who have ever had sexual intercourse with a male (referred to as "sexually experienced women") have used at least one contraceptive method. Over the 20 years from 1982 to 2002, the percent who had ever had a partner who used the male condom increased from 52 to 90 percent. The proportion who had ever had a partner who used withdrawal increased from 25 percent in 1982 to 56 percent in 2002. Another important measure of contraceptive use is use at the first premarital intercourse: before 1980, only 43 percent of women (or their partner) used a method of birth control at their first premarital intercourse. By 1999-2002, the proportion using a method at first premarital intercourse had risen to 79 percent.


DIR Jahrbuch 2004 (Deutsches IVF-Register Annual Report 2004)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2004. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Causes of infertility as predictors of subsequent cancer risk

Abstract: Large retrospective cohort study investigating whether different causes of infertility (endometriosis, anovulation, tubal disease, male factor, cervical/uterine disorders) predict future cancer risk among 12,193 women who sought infertility treatment at five U.S. reproductive endocrinology practices between 1965 and 1988, with cancer incidence tracked through 1999.


Single-dose administration of an aromatase inhibitor for ovarian stimulation

Mohamed F Mitwally

Department of Obstetrics and Gynecology, University of Toronto, and The Samuel Lununfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.


Evidence about extending the duration of oral contraceptive use to suppress  menstruation

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christine L Hitchcock

Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.

Abstract:
Introduction: For many years, individual women and doctors have experimented with extending the duration of active oral contraceptive (OC) pills between pill-free intervals (long OC) to control menstruation. The U.S. approval of an OC with 84 active days and 7 pill-free days in 2003 has attracted considerable media attention. In this review we consider the published evidence on the effectiveness, side effects, and risks of menstrual suppression with long OC.

Methods: We performed a systematic review of published literature on long OC, up to April 2003.

Results: Ten papers were located; two were randomized trials comparing long OC to standard OC; the remaining studies were single-group observational studies. Women on long OC schedules had fewer days of scheduled bleeding during days without pills but more days of unscheduled bleeding and spotting than those on standard OC. These problems were worse for women new to OC and diminished over time. Women on long OC were more likely to discontinue due to poor control of bleeding; women on standard OC were more likely to stop because of problems with headaches. Women on long OC and standard OC both showed increases in physiological factors related to clotting, with a nonsignificant tendency for those on long OC to be more affected. No studies considered the effects of long OC on breast tissue, breast density, endometrial safety, or adolescent maturation and reproductive development. No systematic data were available on the return to reproductive function and fertility after taking long OC. There were no placebo-controlled trials and no information on how long OC compares to normal, unmedicated menstrual cycles. Therefore we believe scientific evidence for safety of long OC use is presently lacking.

Women's Health Issues : Official Publication of the Jacobs Institute of Women's  Health


Neuroendocrinology of nutritional infertility

Abstract: Natural selection has linked the physiological controls of energy balance and fertility such that reproduction is deferred during lean times, particularly in female mammals. In this way, an energetically costly process is confined to periods when sufficient food is available to support pregnancy and lactation. Even in the face of abundance, nutritional infertility ensues if energy intake fails to keep pace with expenditure. A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels (e.g., undereating, excessive energy expenditure, diabetes mellitus) can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors. Decreases in metabolic fuel availability appear to be detected by cells in the caudal hindbrain. Hindbrain neurons producing neuropeptide Y (NPY) and catecholamines (CA) then project to the forebrain where they contact GnRH neurons both directly and also indirectly via corticotropin-releasing hormone (CRH) neurons to inhibit GnRH secretion. In the case of estrous behavior, the best available evidence suggests that the inhibitory NPY/CA system acts primarily via CRH or urocortin projections to various forebrain loci that control sexual receptivity. Disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits, indicating that the circuitry responds to energy deficits and that no signal is necessary to indicate that there is an adequate energy supply. While there is a large body of evidence to support this hypothesis, the data do not exclude nutritional inhibition of reproduction by other pathways and processes, and the full story will undoubtedly be more complex than this.

American journal of physiology. Regulatory, integrative and comparative physiology


Endometriosis

Endometriosis

Abstract: Endometriosis is an oestrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, multiple operations, and infertility. New findings on the genetics, the possible roles of the environment and the immune system, and intrinsic abnormalities in the endometrium of affected women and secreted products of endometriotic lesions have given insight into the pathogenesis of this disorder and serve as the background for new treatments for disease-associated pain and infertility. Affected women are at higher risk than the general female population of developing ovarian cancer, and they also may be at increased risk of breast and other cancers as well as autoimmune and atopic disorders. Clinicians should assess and follow up affected women for these and other associated disorders. There will probably be a new repertoire of approaches for treatment and perhaps cure of this enigmatic disorder in the near future.


A family history of fracture and fracture risk: a meta-analysis

John A Kanis

Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Sheffield, UK. w.j.pontefract@sheffield.ac.uk

Helena Johansson

WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK; Centre for Bone and Arthritis Research (CBAR) at the Sahlgrenska Academy, Institute of Medicine, University of Got...

Eugene McCloskey

The Mellanby Centre for Bone Research, University of Sheffield, Sheffield, U.K.

Huibert AP Pols

Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands

J Reeve

Strangeway's Research Laboratory, Wort's Causeway, Cambridge, United Kingdom

Abstract: The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.


Vitamin D2 is much less effective than vitamin D3 in humans

Laura A G Armas

Creighton University, 601 North 30th Street, Suite 4841, Omaha, Nebraska 68131, USA.

Abstract: Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).

The Journal of Clinical Endocrinology and Metabolism


Risk factors associated with incident clinical vertebral and nonvertebral  fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study  (CaMos)

Kerry Siminoski

Department of Radiology and Diagnostic Imaging & Division of Endocrinology, Department of Internal Medicine, University of Alberta, Edmonton, Alberta, Canada

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract: Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.

Osteoporosis International : a Journal Established As Result of Cooperation  Between the European Foundation for Osteoporosis and the National Osteoporosis  Foundation of the USA


Fertility awareness-based methods for contraception

David A Grimes

University of North Carolina at Chapel Hill

Maria F Gallo

Centers for Disease Control and Prevention

K Nanda

FHI; Clinical Sciences; P.O. Box 13950 Research Triangle Park North Carolina USA 27709

Abstract:
Background: "Fertility awareness-based methods" (FAB) of family planning "involve identification of the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature, or by monitoring cycle days. FAB methods can be used in combination with abstinence or barrier methods during the fertile time" (WHO 2000). Several names have been used to describe this approach to contraception, including "rhythm," "natural family planning" and "periodic abstinence." Fertility awareness-based methods can be used with abstinence from sexual intercourse. Alternatively, they can be used with barrier contraceptives or withdrawal during presumed fertile times.

Objectives: We retrieved and analyzed all randomized controlled trials that examined any fertility awareness-based methods used for contraception. SEARCH STRATEGY: We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, EMBASE, and LILACS (each from its inception to January, 2004) for randomized controlled trials of fertility awareness-based methods. We examined the reference list of each trial as well as that of review articles.
Selection Criteria: We included all randomized controlled trials in any language that compared any fertility awareness-based methods for contraception with a placebo; another method, including an alternative fertility awareness-based method; or fertility awareness-based methods used in conjunction with another contraceptive. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts found for inclusion. We evaluated the methodological quality of the trials for potential biases by qualitatively assessing the study design; randomization method; allocation concealment; blinding; premature discontinuation rates; and loss to follow-up rates. Because of methodological weaknesses, we could not enter the trial results in RevMan, calculate measures of association, or aggregate data.

MAIN Results: Because of poor methods and reporting, pregnancy rates could not be determined. A trial in Colombia found similar numbers of pregnancies among women randomized to the ovulation and symptothermal methods. In contrast, a companion trial in Los Angeles observed more pregnancies in the group assigned to the ovulation method. In the two U.S. trials, recruitment of participants was unexpectedly difficult; this aspect was not mentioned in the report from Colombia. Continuation rates were poor. In the two larger trials, most participants discontinued their assigned method before entering the observation phase of the trial. REVIEWERS'

Conclusions: The comparative efficacy of fertility awareness-based methods of contraception remains unknown. Despite intensive training and ongoing support, most participants in these trials discontinued prematurely. Contraceptive methods should be properly evaluated, preferably in randomized controlled trials, before adoption and dissemination.

The Cochrane Database of Systematic Reviews


Efficacy of the new TwoDay Method of family planning

Abstract:
Objective: To test the efficacy of the TwoDay Method, a new fertility awareness-based method of family planning that provides women with simple instructions to identify the days each cycle when they are most likely to become pregnant. Users avoid unprotected intercourse on days when cervical secretions are present on that day or on the day before, to prevent pregnancy.
Design: Prospective, nonrandomized, multicenter study.
Setting: Five culturally diverse sites in Guatemala, Peru, and the Philippines. PATIENT(S): Four hundred fifty women, aged 18-39 years, wishing to use a fertility awareness-based method to prevent or delay pregnancy. INTERVENTION(S): Study participants were followed for up to 13 cycles of method use. MAIN OUTCOME MEASURE(S): Life table pregnancy rate. RESULT(S): The first-year pregnancy rate was 3.5 (pregnancies per 100 women/years) with correct use of the method (pregnancies and cycles with no intercourse on identified fertile days), 6.3 with use of a backup method on the fertile days, and 13.7 including all cycles and all pregnancies in the analysis. CONCLUSION(S): The TwoDay Method offers a valuable addition to the services that reproductive health and other programs can offer. Its efficacy compares well with that of other coitus-dependent family-planning methods; it is easy to teach, learn, and use; and it can address the need of women for simple, accurate instructions for identifying their fertile days.


The onset of the initial rise in follicle-stimulating hormone during the human  menstrual cycle

F Miro

Unipath Limited, Priory Business Park (FM), Bedford, MK44 3UP, UK. fernando.miro@unipath.com

Abstract:
Background: The rise in FSH (FSHr) that leads to the recruitment of a cohort of follicles during the menstrual cycle occurs during the luteal-follicular transition, however, it is unclear whether it consistently occurs on one particular day, or is subjected to reproductive ageing.

Methods: We determined the FSHr in 836 complete menstrual cycles from 102 women with regular menses using an algorithm, and additionally compared the relative variation in FSH during the last 14 days of the cycle. Possible effects of reproductive ageing on the onset of FSHr were also investigated.

Results: The day of FSHr follows a normal distribution with a median value of -4 (relative to first day of menses), mean -4.1 and SD 2.1. Analysis of the relative changes in FSH during the last 14 days of the cycle revealed the first significant rise on day -4 (P=0.0033), coinciding with the first significant drop in estrogens (P=0.0002). No effect of chronological age, or initial FSH levels, on FSHr was found, however, there was an inverse relationship between total follicular phase length (from day of FSHr to LH peak) and initial FSH levels (P<0.0001).

Conclusions: The initial FSH rise in the cycle occurs consistently 4 days before menses, is related to a drop in estrogen levels, and is not affected by reproductive ageing.


Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic

Abstract:
BACKGROUND: Little is known about the prevalence of specific depressive and anxiety disorders in women before a new course of assisted reproductive technology treatment. Few studies have adopted the proper psychiatric diagnostic procedures.
METHODS: All consecutive women visiting the assisted reproduction clinic of a university-affiliated medical centre, with the intention of starting a new assisted reproduction treatment course, were recruited. A psychiatrist made a diagnosis of psychiatric disorders using a structured interview, the Mini-International Neuropsychiatric Interview (MINI).
RESULTS: Of a total of 112 participants, 40.2% had a psychiatric disorder. The most common diagnosis was generalized anxiety disorder (23.2%), followed by major depressive disorder (17.0%), and dysthymic disorder (9.8%). Participants with a psychiatric morbidity did not differ from those without in terms of age, education, income, or years of infertility. Women with a history of previous assisted reproduction treatment did not differ from those without in depression or anxiety.
CONCLUSIONS: Depressive and anxiety disorders were highly prevalent among women who visited an assisted reproduction clinic for a new course of the treatment. Demographic features and a history of previous assisted reproduction treatment were not risk factors for these psychiatric morbidities in the assisted reproduction clinic.


The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study

Abstract:
OBJECTIVE: Ondansetron (Zofran) is a drug used for the treatment of nausea and vomiting caused by cancer chemotherapy. Despite the fact that it is not indicated, women are being prescribed this drug for the treatment of nausea and vomiting of pregnancy (NVP). There is a paucity of information on fetal safety for this indication. The objective of this study is to determine whether this drug increases the baseline rate of major malformations.

DESIGN: A prospective comparative observational study.

SETTING: Teratogen Information Services (TIS).

POPULATION: Pregnant women.

METHODS: Our three groups included women who were exposed to ondansetron and women exposed to (1) other anti-emetics and (2) non-teratogen exposures. All of the women called either our NVP Helpline or TIS at The Motherisk Program in Toronto, Canada, or The Mothersafe Program in Sydney, Australia.

MAIN OUTCOME MEASURE: Rates of major malformation.

RESULTS: We have completed 176 pregnancy outcomes in each group. In the ondansetron cohort, there were 169 live births, 5 miscarriages, 2 therapeutic abortions, 6 (3.6%) major malformations and the mean birthweight was 3362 g [SD 525]. There were no statistical differences in any of the study endpoints between the ondansetron and the comparison groups.

CONCLUSIONS: This drug does not appear (although the sample size is limited) to be associated with an increased risk for major malformations above baseline.

BJOG : an international journal of obstetrics and gynaecology


Stability of normative data for the SF-36: results of a three-year prospective study in middle-aged Canadians

Hopman WM, Berger C, Joseph L, Towheed T, vandenKerkhof E, Anastassiades T, Cranney A, Adachi JD, Loannidis G, Poliquin S, Brown JP, Murray TM, Hanley DA, Papadimitropoulos EA, Tenenhouse A and the CaMos Research Group.

Abstract:
Background: The SF-36 is widely used to assess health-related quality of life (HRQOL), but with few longitudinal studies in healthy populations, it is difficult to quantify its natural history. This is important because any measure of change following an intervention may be confounded by natural changes in HRQOL. This paper assesses mean changes in SF-36 scores over a 3-year period in men and women between the ages of 40 and 59 years at baseline.

Methods: Subjects were randomly selected from nine Canadian cities. Mean SF-36 changes over a 3-year period (1996/1997-1999/2000) were calculated for each gender within 5-year age categories. Multiple imputation was used to correct for potential bias due to missing data.

Results: The baseline cohort included 1,974 women and 975 men between 40 and 59 years. Mean changes in HRQOL tended to be small. Women demonstrated small average declines in 22 of the 32 age and domain groupings (4 age groups, 8 SF-36 domains) while men showed declines in 14/32. Most participants stayed within 10 points of their original baseline score.

Interpretation: Mean SF-36 scores change only slightly over three years in middle-aged Canadians, although there is much individual variation. It may be necessary to adjust for the natural evolution of SF-36 scores when interpreting results from longitudinal studies. Contexte: Le SF-36 est un court questionnaire très utilisé pour évaluer la qualité de vie liée à la santé (HRQOL). Toutefois, vu le petit nombre d’études longitudinales menées auprès de populations en bonne santé, il est difficile d’évaluer l’histoire naturelle du SF-36, ce qui est important parce que tout changement noté résultant d’une intervention peut être confondu avec des changements normaux de la qualité de vie liée à la santé. Cet article évalue les changements moyens dans les scores des SF-36 sur une période de trois ans chez les hommes et les femmes qui étaient âgés de 40 à 59 ans lors de leur visite initiale. Méthode: Les sujets ont été choisis au hasard dans neuf villes canadiennes. Les changements moyens dans les résultats du SF-36 sur une période de trois ans (1996–1997 à 1999–2000) ont été calculés par sexe et par groupe d’âge de cinq ans. L’imputation multiple a été utilisée pour corriger tout biais résultant d’informations manquantes. Résultats: La cohorte initiale comportait 1 974 femmes et 975 hommes âgés de 40 à 59 ans. Les changements moyens étaient plutôt légers. Chez les femmes, 22 des 32 groupes d’âge et sous-échelles (quatre groupes d’âge, huit sous-échelles SF-36) présentaient de légères diminutions moyennes, alors que chez les hommes, ce nombre était de 14 groupes sur 32. Le score de la plupart des participants est demeuré en deçà de 10 points du score initial lors de l’entrée dans l’étude. Interprétation: Les scores moyens du SF-36 ne changent que légèrement sur une période de trois ans dans la population canadienne d’âge moyen. Toutefois, il pourrait s’avérer nécessaire de tenir compte de l’évolution naturelle des scores du SF-36 lors de l’interprétation des résultats d’études longitudinales.


A meta-analysis of previous fracture and subsequent fracture risk

John A Kanis

Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Sheffield, UK. w.j.pontefract@sheffield.ac.uk

Helena Johansson

WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK; Centre for Bone and Arthritis Research (CBAR) at the Sahlgrenska Academy, Institute of Medicine, University of Got...

Eugene McCloskey

The Mellanby Centre for Bone Research, University of Sheffield, Sheffield, U.K.

J Reeve

Strangeway's Research Laboratory, Wort's Causeway, Cambridge, United Kingdom

Abstract: Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.


Selenium in pregnancy: is selenium an active defective ion against environmental chemical stress?

Abstract: Furthermore, direct questioning and a scrutiny of records of these patients showed that before the full development of the signs of toxaemia—that is, oedema, hypertension, and albuminuria—most had earlier in the pregnancy experienced a symptomatic stage characterized by relatively minor afflictions—for example, lethargy 43%, headache 48%, visual aura 37%, vertigo 29%, nausea and vomiting 16%, irritability 14%, depression 9%, and backache 6%. In fact, only 7% disclosed freedom from these symptoms during a toxaemic pregnancy.


The presence of the antigliadin antibodies in autoimmune thyroid diseases

Abstract:
AIMS: To investigate the presence of the antigliadin antibodies in the patients with Graves' disease and Hashimoto's thyroiditis.

METHODOLOGY: Four hundred patients with autoimmune thyroid disease (280 Graves' disease and 120 Hashimoto's thyroiditis ) were included in the study. The patients with celiac sprue patients were excluded. For the diagnosis of autoimmune thyroiditis, blood levels of thyrotropin (TSH), free thyroxine (FT4), and the titration of thyroid autoantibodies (TgAb and TmAb) were measured, and the thyroid gland was ultrasonographycally evaluated. After the diagnosis of autoimmune thyroid disease was established, the titration of antigliadin antibodies (Ig A and B) were routinely detected.

RESULTS: Twenty two patients (5.5 per cent) with autoimmune thyroiditis had positive antigliadin antibodies. Polyglandular endocrine syndrome was diagnosed in most of these patients.

CONCLUSIONS: We claim that polyglandular endocrine syndrome is the commonest cause of positivity of antigliadin antibodies in the patients with autoimmune thyroid disease.


von Willebrand disease in women with menorrhagia: a systematic review

Abstract:
OBJECTIVE: To determine the prevalence of von Willebrand disease in women presenting with menorrhagia.

DESIGN: Systematic review of studies evaluating the prevalence of von Willebrand disease in women with menorrhagia.

SETTING: Hospital outpatient clinics (mainly gynaecological) and population surveys.

POPULATION: Women presenting with menorrhagia.

METHODS: Relevant studies were extracted from MEDLINE search, bibliographies of identified articles and published proceedings of meetings and conferences.

MAIN OUTCOME MEASURES: Number of women with von Willebrand disease.

RESULTS: Eleven studies were included, totalling 988 women with menorrhagia. One hundred and thirty-one women were diagnosed to have von Willebrand disease with prevalences in individual studies ranging from 5% to 24%. The overall prevalence was 13% (95% CI 11-15.6%). The prevalence was higher in the European studies-18% (95% CI 15-23%) compared with that in North American studies-10% (95% CI 7.5-13%). This difference (P= 0.007) is likely to be the result of differences in the studies, which include method of recruitment of study population, method of assessing menstrual blood loss ethnic composition of study population, criteria for diagnosis and use of race- and ABO blood group-specific values for von Willebrand factor.

CONCLUSIONS: The prevalence of von Willebrand disease is increased in women with menorrhagia and is the underlying cause in a small but significant group of women with menorrhagia across the world. Testing for this disorder should be considered when investigating women with menorrhagia, especially those of Caucasian origin, those with no obvious pelvic pathology or with additional bleeding symptoms.


Proactive management of menstrual cycle abnormalities in young women

Abstract: The goal of an integrative science of women's health is bringing together childbearing with women's health during the lifespan. Enhancing a woman's ability to conceive and maintain a pregnancy is influenced by decisions made well before the beginning of a pregnancy. Identifying ovulatory disorders makes it possible to intervene early in a young woman's childbearing years. Gynecologic charting typically used in natural family planning provides information to the woman and to the healthcare provider that is useful for diagnosis. If young women have a better understanding of fertility and menstrual cycle function, they are in a stronger position to make informed decisions about how they wish to manage their reproductive and sexual health. It may be possible to educate the young woman in health habits that will lead to a healthy pregnancy when she chooses and/or to treat the cause of the ovulatory disorder. This article focuses on polycystic ovary syndrome and hypothalamic dysfunction which can cause menstrual cycle abnormalities in which gynecologic charting is useful in young women.

The Journal of Perinatal & Neonatal Nursing


A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia

Abstract:
OBJECTIVE: To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia.

DESIGN: Placebo-controlled double-blind randomized trial.

SETTING: University tertiary referral center.

PATIENT(S): Sixty infertile patients (aged 20-40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study.

INTERVENTION(S): Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up.

MAIN OUTCOME MEASURE(S): Variation in the semen parameters that were used for patient selection.

RESULT(S): Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate).

CONCLUSION(S): Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.


Adhesion-related readmissions following gynaecological laparoscopy or laparotomy in Scotland: an epidemiological study of 24 046 patients

Surgical and Clinical Research (SCAR) Group

Abstract:
Background: Gynaecological laparotomies are associated with considerable adhesion-related burdens; however, few data are available concerning laparoscopic surgery. This study evaluated the epidemiology of adhesion-related readmissions following open and laparoscopic procedures.

Methods: Records from 24,046 patients undergoing gynaecological surgery in Scottish National Health Service hospitals during 1996 were assessed retrospectively. Cohorts comprised 15,197 patients undergoing laparoscopic surgery and 8849 patients undergoing laparotomies. Adhesion-related readmission episodes (directly and possibly related) were assessed over 4 years following initial surgery and were expressed as percentages of the number of initial procedures.

Results: Directly adhesion-related readmissions 1 year after initial laparoscopic surgery were: in the high-risk group (adhesiolysis and cyst drainage) 1.3%; medium-risk (therapeutic and diagnostic procedures not categorized as highor low-risk) 1.5%; and low-risk (Fallopian tube sterilizations) 0.2%. Readmissions for laparotomy following surgery on the Fallopian tubes were 0.9%, ovaries 2.1%, uterus 0.6% and vagina 0%. Readmissions occurred at reduced rates in the second, third and fourth years after surgery. Exclusion of patients who underwent surgery within the previous 5 years resulted in reduced readmission rates following laparotomy and high-risk laparoscopy.

Conclusions: With the exception of laparoscopic sterilizations, open and laparoscopic gynaecological surgery are associated with comparable risks of adhesion-related readmissions.


Smoking and fracture risk: a meta-analysis

Abstract: Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.


A meta-analysis of prior corticosteroid use and fracture risk

Huibert AP Pols

Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands

Mellstrom D and the CaMos Research Group

Abstract:
The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.
Introduction: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk.

Materials and Methods: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients.

Results: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD.

Conclusion: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.

Journal of Bone and Mineral Research : the Official Journal of the American  Society for Bone and Mineral Research