Risk of breast cancer associated with short-term use of oral contraceptives

Suzanne G. Folger

National Center for Chronic Disease Prevention and Health Promotion

Leslie Bernstein

Centers for Disease Control and Prevention

Giske Ursin

Division of Cancer Etiology, Department of Population Sciences, City of Hope Medical Center, Duarte, California; Departments of 2Preventive Medicine and 3Pathology, Keck School of Medicine, Univers...

Abstract:
Objective: To estimate breast cancer risk associated with short-term (<6 months) oral contraceptive use, and explore variation in estimates by use characteristics and medical, menstrual, and reproductive history.

Methods: We analyzed data from the Women's Contraceptive and Reproductive Experiences Study. Case subjects were white women and black women, 35-64 years old, diagnosed with invasive breast cancer in July 1994-April 1998. Control subjects identified by random-digit dialing were matched to case subjects by age, race, and study site. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Overall, short-term oral contraceptive use was not associated with breast cancer risk (OR = 1.0; 95% CI = 0.8-1.1). However, significant interaction between short-term use and menopausal status led to an observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI = 1.0-1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6-1.0) associated with short-term use. The association was more pronounced in women with non-contraceptive reasons for use and underlying risk factors for breast cancer.

Conclusions: These associations may result from underlying characteristics of users or unmeasured factors influencing duration of use and breast cancer risk.


Hormonal contraception and the risk of HIV acquisition

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) Study Group

Abstract:
Background: Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known.

Objective: To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections.

Methods: This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases).

Results: HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group.

Conclusions: No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.


Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa

Abstract: Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The inflammatory reactions within the male genital tract are inevitably connected with oxidative stress. Growing evidence indicates that imbalance between prooxidative and anti-oxidative substances in semen leads to metabolic and functional disorders of male germ cells and may be a primary cause of some types of infertility. The infectious factor and local tissue damage can lead to the infiltration of leukocytes to the inflammatory site. This is in an obvious way connected to the production and release of large amounts of reactive oxygen species (ROS), which trigger immune responses directed against the infectious agent, and the simultaneous secretion of numerous biological substances, thereby escalating the inflammation. Some of these factors are proteases and proinflammatory cytokines. Extended exposure of spermatozoa to ROS may lead to the peroxidation of sperm membrane lipids. Many studies point to the combined activities of inflammatory mediators in exerting toxic effects on spermatozoa. The local influences of biologically active substances released by activated leukocytes in the course of the inflammatory response and the mutual interactions of various factors (bacteria, leukocytes, proinflammatory cytokines) at the site represent a complex puzzle.


The underlying cause of cervical cancer in oral contraceptive users may be related to cervical mucus changes

Abstract: Oral contraceptives (OCs) remain among the most effective reversible methods of birth control available today, providing almost 100% effectiveness with an impressively high margin of safety and other important health benefits. However, concerns have been raised about the role that the hormones in OCs might play in the pathogenesis of cervical cancer. Evidence shows that long-term use of OCs (five or more years) may be associated with an increased risk of cancer of the cervix. The mechanism of increased risk of cervical cancer in OCs users has long been debated, and remains uncertain. Our hypothesis is that scanty, thick, and highly viscous cervical mucus obtained in OCs users intimately involved in the pathogenesis of cervical cancer. Possibly, this architecture of cervical mucus may modulate and prolong the effect of carcinogenic agents, which have been carried by coitus and stored in posterior vaginal fornix, on squamocolumnar junction of cervix by not permitting them to be removed because of its highly viscous pattern. The role of cervical mucus changes by means of specific mucin protein changes on the pathophysiology of cervical cancer in OCs users should be investigated.


Walking the talk: Doing science with perimenopausal women and their health care providers

Christine L Hitchcock

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: No AccessOther Health Study28 Jun 2021Walking the TalkReimagining Primary Health Care After COVID-19Authors/Editors: World BankWorld Bankhttps://doi.org/10.1596/35842SectionsAboutPDF (22.7 MB) ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked In Abstract: The world has waited long enough for high-performing primary health care (PHC). It's time to deliver. Forty years ago, leaders embraced the promise of health for all through PHC. That vision has inspired generations. But for nearly half a century, countries have struggled to walk the talk on PHC. We have not built health systems anchored in strong PHC where they were needed most. Today, COVID-19 (coronavirus) has brought the reckoning for that shared failure—but also the chance to do the job right at last. The pandemic has shown policy makers and ordinary citizens why health systems matter and what happens when they fail. By doing so, it has also created a oncein-a-generation chance for structural health-system change. Bold reforms now can prepare health systems for future crises and bring goals like universal health coverage (UHC) within reach. PHC holds the key to these transformations. But to fulfill that promise, the walk has to finally match the talk. This report charts an agenda toward reimagined, fit-for-purpose PHC. It asks three questions about health-systems reform built around Phc: "Why?", "What?", and "How?" Since PHC has been around for decades, why write a thick report about it now? The answer is that the characteristics of high-performing PHC are exactly those that are most critical for managing the pressures coming to bear on health systems in the post-COVID world. The challenges include future infectious outbreaks and other emergent threats, but also long-term structural trends that are reshaping the environments in which systems operate in non-crisis times. This report highlights three sets of megatrends that will increasingly affect health systems in the decades ahead: demographic and epidemiological shifts; changes in technology; and citizens' evolving expectations for health care. Previous bookNext book FiguresreferencesRecommendeddetails View Published: June 2021 Copyright & Permissions Related TopicsHealth Nutrition and Population KeywordsCORONAVIRUSCOVID-19ACCOUNTABILITYHEALTH CARE REFORM PDF DownloadLoading ...


Oral Contraceptives and Cardiovascular Risk (AHA Abstract)


Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy (IARC Monograph Vol 91)

International Agency for Research on Cancer


Vitamin D deficiency in a healthy group of mothers and newborn infants

Abstract: Plasma 25-hydroxyvitamin D was measured in 40 healthy, mostly Black, mother-infant pairs. Although a majority of mothers received a daily prenatal multivitamin, vitamin D deficiency (<30 nmol/L), was found in 50% of mothers and 65% of their newborn infants, with a positive correlation between maternal and infant plasma 25-hydroxyvitamin D concentrations. Maternal vitamin D deficiency may represent an important risk factor for the development of rickets in children.


Dietary fatty acid intakes and the risk of ovulatory infertility

Abstract:
Background: Pharmacologic activation of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) improves ovulatory function in women with polycystic ovary syndrome, and specific dietary fatty acids can affect PPAR-gamma activity.

Objective: The objective of the study was to assess whether the intakes of total fat, cholesterol, and major types of fatty acids affect the risk of ovulatory infertility.

Design: We conducted a prospective cohort study of 18 555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999. Diet was assessed twice during follow-up by using a food-frequency questionnaire.

Results: During follow-up, 438 incidents of ovulatory infertility were reported. In logistic regression analyses, intakes of total fat, cholesterol, and most types of fatty acids were not related to ovulatory infertility. Each 2% increase in the intake of energy from trans unsaturated fats, as opposed to that from carbohydrates, was associated with a 73% greater risk of ovulatory infertility after adjustment for known and suspected risk factors for this condition [relative risk (RR) = 1.73; 95% CI: 1.09, 2.73]. Obtaining 2% of energy intake from trans fats rather than from n-6 polyunsaturated fats was associated with a similar increase in the risk of ovulatory infertility (RR = 1.79; 95% CI: 1.11, 2.89). In addition, obtaining 2% of energy from trans fats rather than from monounsaturated fats was associated with a more than doubled risk of ovulatory infertility (RR = 2.31; 95% CI: 1.09, 4.87).Conclusiontrans Unsaturated fats may increase the risk of ovulatory infertility when consumed instead of carbohydrates or unsaturated fats commonly found in nonhydrogenated vegetable oils.

The American Journal of Clinical Nutrition


DIR Jahrbuch 2006 (Deutsches IVF-Register Annual Report 2006)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2006. 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).


Combined estrogen-progestogen contraceptives and combined estrogen-progestogen menopausal therapy

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans

IARC monographs on the evaluation of carcinogenic risks to humans


Veerle Goossens

Abstract: 30. Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE. Andersen AN(1), Goossens V, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG. (1)Central Office, European Society of Human Reproduction and Embryology, Meerstraat 60, B-1852 Grimbergen, Belgium. bruno.vandeneede@eshre.com BACKGROUND: European results of assisted reproductive techniques (ARTs) from treatments initiated during 2003 are presented in this seventh report. METHODS: Data were mainly collected from already existing national registers. From 28 countries, 725 clinics reported 365 103 treatment cycles with: IVF 132 932, ICSI 162 149, frozen embryo replacement (FER) 60 412, oocyte donation (OD) 7548, PGD/PGS 1956 and IVM 109. Overall, this represents a 13% increase since 2002. For the third time, results on European data on intrauterine inseminations (IUIs) were reported from 19 countries. A total of 99 577 cycles (IUI-H, 82 834; IUI-D, 16 743) were included. RESULTS: In those 15 countries where all clinics reported to the register, a total of 284 765 cycles were performed in a population of 278.7 million, corresponding to 1022 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.1 and 29.6%, respectively. For ICSI, the corresponding rates were 26.5 and 28.7%. After IUI-H, the clinical pregnancy rate was 12.2% in women below 40 years and 8.8% in women > or =40 years. After IVF and ICSI, the distribution of transfer of one, two, three and four or more embryos was 15.7, 55.9, 24.9 and 3.5%, respectively. Compared to the year 2002, fewer embryos were transferred, but huge differences still exist between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 76.7, 22.0 and 1.1%, respectively. This gives a total multiple delivery rate of 23.1% compared with 24.5% in 2002. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 4.4% between countries. After IUI-H in women below 40 years of age, 11.4% were twin and 2.2% triplet gestations.


Prospective study of hormonal contraception and women's risk of HIV infection in South Africa

Abstract:
Background: Many women using hormonal contraceptives are also at risk of sexually transmitted HIV infection, but data are mixed on whether hormonal contraception increases women's risk of HIV. We investigated associations between HIV incidence and use of combined oral contraceptives (COC), norethindrone enanthate (NET-EN) or depot medroxyprogesterone acetate (DMPA) in a cohort of South African women.

Methods: Participants were 4200 HIV-negative women aged 35-49 years enrolled into a cervical cancer screening trial. At enrollment, women were tested for sexually transmitted infections and reported on their sexual behaviour and contraceptive use. During the 24 months of follow-up, women reported on their sexual behaviours and contraceptive use and underwent repeat HIV testing.

Results: During the 5010 person-years of follow-up, 111 incident HIV infections were observed (HIV incidence, 2.2 infections/100 person-years). At enrollment, 21% of women reported using hormonal contraception, primarily DMPA (14% of all women) or NET-EN (5%). After adjusting for sexual risk behaviours and sexually transmitted infections, the incidence of HIV was similar among women using COC, NET-EN or DMPA compared with women not using any hormonal method [incidence rate ratios and 95% confidence intervals, 0.65, 0.16-2.66; 0.79, 0.31-2.02 and 0.96, 0.58-1.59, respectively]. There was also no association between increased duration of DMPA use and HIV incidence (P-value for trend, 0.51).

Conclusions: These findings contribute to the evidence from general population cohorts of women that hormonal contraceptive use is not associated with increased risk of HIV acquisition. Nonetheless, family planning services are an important venue for HIV prevention activities.


Metformin reduces abortion in pregnant women with polycystic ovary syndrome

Abstract:
BACKGROUND: Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin - owing to its metabolic, endocrine, vascular and anti-inflammatory effects - may reduce the incidence of first-trimester abortion in PCOS women.

MATERIALS AND METHODS: A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000-2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group.

RESULTS: Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11-0.42).

CONCLUSIONS: Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.

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


FSH and bone--important physiology or not?

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: For many years, osteoporosis in women was equated with estrogen deficiency. The recent articles by Zaidi and colleagues offer a new challenge to the estrogen-deficiency-osteoporosis hypothesis by showing that follicle-stimulating hormone (FSH) stimulates osteoclastic bone resorption perhaps through tumor necrosis factor-alpha (TNF-alpha). These authors, however, neglected to mention bone abnormalities and high testosterone levels that were previously shown in FSH-receptor knockout and other modified mice. It is also possible that they have overemphasized potential relationships of these new data with human bone loss. Despite these fascinating data, the paradigm of FSH causing hypogonadal bone loss is not yet ready to displace the estrogen-deficiency-osteoporosis paradigm, although that model already faces considerable challenge.


Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men

Abstract: Ascorbic acid has recently been reported to protect sperm DNA from the damage induced by exogenous oxidative stress in vitro. But, there is no report on seminal ascorbic acid and sperm DNA fragmentation in infertile men. In this study, we asked whether sperm DNA damage correlates with seminal ascorbic acid levels. Sperm DNA fragmentation index (DFI) was analysed in 75 men by flow cytometry after acridine orange staining. We also measured the levels of seminal plasma ascorbic acid and total antioxidant capacity. Abnormal sperm DNA integrity (DFI >or= 30%) was observed in 12% of the patients with normal semen parameters and in 52% of the patients with abnormal semen parameters. There were significant correlations between the level of DFI and conventional semen parameters including sperm count, motility and morphology (r = -0.29, -0.55 and -0.53 respectively; p < 0.05). Seminal ascorbic acid level was significantly lower in the patients with leucospermia than the patient with normal semen parameters. Interestingly, a significantly greater percentage of men with abnormal DFI were observed in the patients with low levels of seminal ascorbic acid compared with those with normal or high levels of ascorbic acid (59% vs. 33%, p < 0.05). Men with insufficient seminal ascorbic acid frequently have sperm DNA damage.


Recent Declines in Hormone Therapy Utilization and Breast Cancer Incidence: Clinical and Population-Based Evidence


What is the number of older Canadians needed to screen by measurement of bone  density to detect an undiagnosed case of osteoporosis? a population-based study  from CaMos

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract: Routine bone mineral densitometry (BMD) screening has been recommended for women aged >or=65 yr (Osteoporosis Canada [OC], International Society for Clinical Densitometry [ISCD], Canadian and United States Task Forces on Preventative Healthcare, and National Osteoporosis Foundation) and for men >or=65 yr (OC) or >or=70 yr (ISCD). We estimated the number of older Canadians needed to screen (NNS) by BMD to detect an undiagnosed case of osteoporosis, using prospective, multicenter, population-based data from the Canadian Multicentre Osteoporosis Study (CaMos). We included participants aged >or=65 yr with baseline dual-energy X-ray absorptiometry (DXA) BMDs at the femoral neck and lumbar spine (L1-L4). Osteoporosis was defined by a T-score or=65 yr. The percentage prevalence and 95% confidence intervals were determined. In individuals aged >or=65 yr, the prevalence of osteoporosis was 25.6% in women (95% confidence interval, 24.0%, 27.3%) and 8.9% in men (7.3%, 10.8%). In 652 men aged >or=70 yr, the prevalence of osteoporosis was 11.3% (9.1%, 14.0%). Of the participants with BMD-defined osteoporosis, 76.6% of woman aged >or=65 yr (73.2%, 79.6%; 516 of 674 women), 93.4% of men aged >or=65 yr (86.4%, 96.9%; 85 of 91), and 93.2% of men >or=70 yr (84.9%, 97.0%; 68 of 73) were not aware of it. Thus, the minimum NNS by BMD testing to detect one previously undiagnosed case of osteoporosis in Canada is: 6 women aged >or=65 yr, 13 men aged >or=65 yr, and 10 men aged >or=70 yr.

Journal of Clinical Densitometry : the Official Journal of the International  Society for Clinical Densitometry


Menstruation in girls and adolescents: using the menstrual cycle as a vital sign

American Academy of Pediatrics Committee on Adolescence

American College of Obstetricians and Gynecologists Committee on Adolescent Health Care

Abstract: Young patients and their parents often are unsure about what represents normal menstrual patterns, and clinicians also may be unsure about normal ranges for menstrual cycle length and amount and duration of flow through adolescence. It is important to be able to educate young patients and their parents regarding what to expect of a first period and about the range for normal cycle length of subsequent menses. It is equally important for clinicians to have an understanding of bleeding patterns in girls and adolescents, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate young patients' conditions appropriately. Using the menstrual cycle as an additional vital sign adds a powerful tool to the assessment of normal development and the exclusion of pathological conditions.


What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis

Abstract: OBJECTIVE: To investigate the reasons women experience delays in the diagnosis of endometriosis and the impact of this. DESIGN: A qualitative interview-based study of 32 women, 28 of whom were subsequently diagnosed with endometriosis. SETTING: Southeast England. PATIENT(S): Women attending a pelvic pain clinic. INTERVENTION(S): Semistructured interviews. MAIN OUTCOME MEASURE(S): Women's reported experiences of being diagnosed with endometriosis. RESULT(S): Delays in the diagnosis of endometriosis occur at an individual patient level and a medical level, as both women and family doctors normalize symptoms, symptoms are suppressed through hormones, and nondiscriminatory investigations are relied upon. Women benefited from a diagnosis, because it provided a language in which to discuss their condition, offered possible management strategies to control symptoms, and provided reassurance that symptoms were not due to cancer. Diagnosis also sanctioned women's access to social support and legitimized absences from social and work obligations. CONCLUSION(S): Although recent guidelines for the management of chronic pelvic pain suggest that diagnostic laparoscopy may be considered a secondary investigation after the failure of therapeutic interventions, the present study highlights the importance of an early diagnosis for women who suffer at physical, emotional, and social levels when they remain undiagnosed.


Salpingectomy for Hydrosalpinx Prior to IVF


Infertility and assisted reproduction in Denmark. Epidemiology and psychosocial consequences

Abstract: Clinically a couple is considered to be infertile after at least one year without contraception and without pregnancy. There was scant knowledge about the prevalences of infertility, involuntary childlessness and the seeking of fertility treatment and only few longitudinal studies about the psychosocial consequences of infertility and its treatment. This thesis is about the epidemiological aspects of infertility; the conceptualization and measurement of important psychosocial aspects of infertility; and a medical sociological analysis of the associations between these psychosocial variables among Danish women and men in fertility treatment. The thesis is based on nine papers. The three main purposes were: (i) to review critically, population based studies of infertility and medical care seeking in industrialised countries. Further, to examine these prevalences and subsequent motherhood among women in former assisted reproduction in a Danish population. (ii) To develop measures of psychosocial consequences of infertility: fertility problem stress, marital benefit, communication, coping strategies, attitudes to and evaluation of fertility treatment. (iii) To examine these phenomena and to analyse their interrelations among Danish women and men in fertility treatment. The thesis is based on four empirical studies: (i) The Women and Health Survey, a cross-sectional population-based study among 15-44 year old women (n=907, 25-44 year old) in Copenhagen County, 1989. (ii) The Psychosocial Infertility Interview Study, a qualitative interview study among 16 couples (n=2 participants) infertility treatment at The Fertility Clinic, Herlev University Hospital,1992. (iii) The Infertility Cohort, a longitudinal cohort study consecutively including all couples (n=250 participants) beginning anew fertility treatment period at one of four public (Braedstrup, Herlev, Odense, Rigshospitalet) and one private fertility clinic (Trianglen),2000-2002. (iv) The Communication and Stress Management Training Programme, an intervention study among couples(n=74 participants) in fertility treatment at The Fertility Clinic, The Juliane Marie Centre, Rigshospitalet, 2001-2003. Included is also a literature review of population-based infertility studies from industrialised countries. Data from (iii) and (iv) are studies from The Copenhagen Multi-centre Psychosocial Infertility (COMPI) Research Programme (www.compipro.dk). Epidemiological and demographic studies investigating the prevalences of infertility differed in how they defined the numerator (the infertile participants) and the denominator (the population at risk). It was important to calculate reliable estimates of the infertility prevalence by including only women who had tried to have at least one child in the population at risk, as a notable proportion of women in the fertile ages had not (yet) attempted to become a mother. The lifetime prevalence of infertility in the representative population-based study was 26.4%. In the age group 35 to 44 years 5.8% were primarily involuntarily in fecund (involuntarily childless). Even in a country with access to fertility treatment in a public health-care system without self-payment lower education was a predictor of lower treatment seeking. In the cohort study (2000-2002)of couples starting a new period of assisted reproduction treatment 62.6% reported a treatment-related pregnancy at the one-year follow-up. In total 32.4% reported a treatment-related delivery. In total 24.2% reported a current continuing pregnancy and spontaneous pregnancies accounted for 2.7% of these. We developed measures of fertility problem stress, marital benefit(that infertility has brought the partners closer together and strengthened their marriage), partner communication, infertility related communication, coping strategies, attitudes to fertility treatment and evaluation of care. The medical sociological analyses showed that the variables of psychosocial consequences of infertility and treatment are interwoven with each others in a complex pattern, a pattern that both differed and was similar when comparing women and men. The infertility-related communication strategy (secrecy, formal, open-minded)identified in the qualitative interviews was later confirmed in the COMPI Infertility Cohort. Using the formal strategy and not talking about the emotional aspects of infertility and its treatment suggested high fertility problem stress. The coping strategies studied showed significant social differences and active-avoidance coping was a significant predictor of high fertility problem stress. A positive effect of infertility on the marriage, marital benefit was common. Men using the secrecy communication strategy had increased risk of low marital benefit. Difficult partner communication was a significant predictor of high fertility problem stress and among men, of low marital benefit. The intervention study showed that it was possible for the participants to change their communication with partner and other people close to them and that participants achieved an increased awareness of what, how much and when to discuss with others. High fertility problem stress and high marital benefit were associated with high importance ratings of patient-centred care and intentions to use professional psychosocial services. Among women, high fertility problem stress was a predictor of lower satisfaction ratings with fertility treatment. High marital benefit was a predictor of high satisfaction ratings of both medical and patient-centred care. In conclusion, infertility is a common experience among couples attempting to become parents. Assisted reproduction in the public health-care system in Denmark has high success rates, i.e. pregnancies,deliveries and high patient satisfaction. A large minority of people in fertility treatment experience high fertility problem stress,and some use communication and coping strategies that predicts high stress. Developing and evaluating different psychosocial interventions are necessary to offer the psychosocial support needed for this minority of fertility patients.


Low-Dose Naltreoxone for the Treatment of Irritable Bowel Syndrome: A Pilot Study

Abstract: Preclinical studies have shown that a very low dose of naltreoxone hydrochloride (NTX), an opiate antagonist, can block excitatory opioid receptors without affecting inhibitory opioid receptors, resulting in analgesic potency without side effects. The present study assessed the efficacy and safety of PTI-901 (low-dose NTX) treatment in Irritable bowel syndrome (IBS) patients. Forty-two IBS patients participated in an open-label study. Participants received 0.5 mg PTI-901/day for 4 weeks and were evaluated during baseline, during treatment, and at 4-week follow-up. Patients recorded degree of abdominal pain, stool urgency, consistency, and frequency. Primary outcomes were number of pain-free days and overall symptom relief, evaluated by a global assessment score. Data were analyzed per protocol. Global assessment improved in 76% of 42 patients. During treatment, the mean weekly number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 (P=0.011). There were no significant adverse reactions. PTI-901 improves pain and overall feeling, and is well tolerated by IBS patients. A large, randomized, double-blind, placebo-controlled study is justified.


Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites

Abstract:
BACKGROUND: Phthalates are multifunctional chemicals used in a variety of consumer, medical, and personal care products. Previously, we reported dose-response associations of decreased semen quality with urinary concentrations of monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study extends our work in a larger sample of men and includes measurements of di(2-ethylhexyl) phthalate (DEHP) oxidative metabolites.

METHODS: Between January 2000 and May 2004, we recruited 463 male partners of subfertile couples who presented for semen analysis to the Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values for sperm concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg Kruger Strict criteria for morphology (<4% normal). The comparison group was men with all 3 semen parameters above the reference values. In a single spot urine sample from each man, phthalate metabolites were measured using solid-phase extraction coupled to high-performance liquid chromatography isotope-dilution tandem mass spectrometry.

RESULTS: There were dose-response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04) and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP metabolites with these semen parameters.

CONCLUSION: The present study confirms previous results on the relationship of altered semen quality with exposure to MBP at general population levels. We did not find associations between semen parameters and 3 DEHP metabolites.


Perimenopause lost—reframing the end of menstruation

Abstract: Ordinary women and official statements confuse and conflate perimenopause—the long, complex, life phase of higher and chaotic estrogen levels—with the low and stable estrogen levels of menopause. This paints both perimenopause and menopause with an inaccurate ‘estrogen deficiency’ brush. Menopause is the hormonal, and (except for hot flushes) the experiential opposite of perimenopause. This feminist analysis is from my perspective as physician‐scientist who experienced a perimenopause that was scientifically enlightening, but personally agonizing. Denial of perimenopausal and menopausal differences causes perimenopause to be ‘lost’ in several ways: (1) we may assume that perimenopause is chronic rather than ending in a largely asymptomatic menopause; (2) societal taboos isolate us, depriving us of solidarity with perimenopause ‘survivors’; (3) we are told we have dropping estrogen levels when our experiences, like pregnancy dreams, tell us the opposite; (4) gynaecology treats heavy flow with estrogen despite higher perimenopausal estrogen levels; (5) feminists ignore hormonal changes and attribute perimenopausal symptoms to (real) stresses of inferior social status and ageing; and (6) many of us thus become menopausal without the unique, self‐actualization experience that perimenopause has the potential to provide. Thus perimenopause—a valuable transition into knowing and standing up for ourselves—becomes lost.

Journal of reproductive and infant psychology


Measuring fecundity with standardised estimates of expected pregnancies

Abstract: Approaches to measuring fecundity include the assessment of time to pregnancy and day-specific probabilities of conception (daily fecundities) indexed to a day of ovulation. In this paper, we develop an additional approach of calculating expected pregnancies based on daily fecundities indexed to the last day of the menstrual cycle. Expected pregnancies can thus be calculated while controlling for frequency and timing of coitus. Comparing observed pregnancies with expected pregnancies allows for a standardised comparison of fecundity between studies or groups within studies, and can be used to assess the effects of categorical covariates on the woman or couple level, and also on the cycle level. This can be accomplished in a minimal data set that does not necessarily require hormonal measurement or the explicit identification of ovulation. We demonstrate this approach by examining the effects of age and parity on fecundity in a data set from women monitoring their fertility cycles with the Creighton Model FertilityCare System.


Estimation of the day-specific probabilities of conception: current state of the  knowledge and the relevance for epidemiological research

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract: Conception, as defined by the fertilisation of an ovum by a sperm, marks the beginning of human development. Currently, a biomarker of conception is not available; as conception occurs shortly after ovulation, the latter can be used as a proxy for the time of conception. In the absence of serial ultrasound examinations, ovulation cannot be readily visualised leaving researchers to rely on proxy measures of ovulation that are subject to error. The most commonly used proxy measures include: charting basal body temperature, monitoring cervical mucus, and measuring urinary metabolites of oestradiol and luteinising hormone. Establishing the timing of the ovulation and the fertile window has practical utility in that it will assist couples in appropriately timing intercourse to achieve or avoid pregnancy. Identifying the likely day of conception is clinically relevant because it has the potential to facilitate more accurate pregnancy dating, thereby reducing the iatrogenic risks associated with uncertain gestation. Using data from prospective studies of couples attempting to conceive, several researchers have developed models for estimating the day-specific probabilities of conception. Elucidating these will allow researchers to more accurately estimate the day of conception, thus spawning research initiatives that will expand our current limited knowledge about the effect of exposures at critical periconceptional windows. While basal body temperature charting and cervical mucus monitoring have been used with success in field-based studies for many years, recent advances in science and technology have made it possible for women to get instant feedback regarding their daily fertility status by monitoring urinary metabolites of reproductive hormones in the privacy of their own homes. Not only are innovations such as luteinising hormone test kits and digital fertility monitors likely to increase study compliance and participation rates, they provide valuable prospective data that can be used in epidemiological research. Although we have made great strides in estimating the timing and length of the fertile window, more work is needed to elucidate the day-specific probabilities of conception using proxy measures of ovulation that are inherently subject to error. Modelling approaches that incorporate the use of multiple markers of ovulation offer great promise to fill these important data gaps.


Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis

Chris Kahlenborn

The Polycarp Research Institute, Enola, PA, USA

Walter B Severs

Penn State Milton S. Hershey Medical Center

Abstract:
OBJECTIVE: To perform a meta-analysis of case-control studies that addressed whether prior oral contraceptive (OC) use is associated with premenopausal breast cancer.

METHODS: We searched the MEDLINE and PubMed databases and bibliography reviews to identify case-control studies of OCs and premenopausal breast cancer published in or after 1980. Search terms used included breast neoplasms, oral contraceptives, contraceptive agents, and case-control studies. Studies reported in all languages were included. Thirty-four studies were identified that met inclusion criteria. Two reviewers extracted data from original research articles or additional data provided by study authors. We used the DerSimonian-Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs) and the Mantel-Haenszel test to assess association between OC use and cancer.

RESULTS: Use of OCs was associated with an increased risk of premenopausal breast cancer in general (OR, 1.19; 95% CI, 1.09-1.29) and across various patterns of OC use. Among studies that provided data on nulliparous and parous women separately, OC use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI, 1.20-1.40) and nulliparous (OR, 1.24; 95% CI, 0.92-1.67) women. Longer duration of use did not substantially alter risk in nulliparous women (OR, 1.29; 95% CI, 0.85-1.96). Among parous women, the association was stronger when OCs were used before first full-term pregnancy (FFTP) (OR, 1.44; 95% CI, 1.28-1.62) than after FFTP (OR, 1.15; 95% CI, 1.06-1.26). The association between OC use and breast cancer risk was greatest for parous women who used OCs 4 or more years before FFTP (OR, 1.52; 95% CI, 1.26-1.82).

CONCLUSION: Use of OCs is associated with an increased risk of premenopausal breast cancer, especially with use before FFTP in parous women.


It's all in the timing: coital frequency and fertility awareness-based methods of  family planning

Abstract: Fertility awareness-based methods of family planning help women to identify the days of the cycle they should avoid unprotected intercourse to prevent pregnancy. Therefore using fertility awareness-based methods influences the timing of sexual activity, which may affect the nature of the sexual relationship. Data are used from the clinical trials of two fertility awareness-based methods--the Standard Days Method and the TwoDay Method--to determine the frequency and timing of intercourse during the cycle, and the determinants of coital frequency. The mean coital frequency of study participants was similar to that reported by users of other methods. Results suggest that coital frequency increases with consecutive cycles of method use. At the same time the frequency of intercourse during the identified fertile days and during menses decreases. This evidence implies a behavioural change as couples get more experience using their method and communicating about the fertile days. Coital frequency was also influenced by the method used and by the study sites. Potential differences between the methods and sites that may contribute to this effect are discussed.


The case against ergocalciferol (vitamin D2) as a vitamin supplement

Abstract: Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D2. The case that vitamin D2 should no longer be considered equivalent to vitamin D3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.

The American Journal of Clinical Nutrition


BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer  before age 50

Haile RW, Thomas DC, McGuire V, Felberg A, John EM, Milne RL, Hopper JL, Jenkins MA, Levine AJ, Daly MM, Buys SS, Senie RT, Andrulis IL, Knight JA, Godwin AK, Southey M, McCredie MR, Giles GG, Andrews L, Tucker K, Miron A, Apicella C, Tesoriero A, Bane A, Pike MC, Whittemore AS

Abstract:
Background: Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice.

Methods: We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years.

Results: For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P(trend) = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (OR(trend) per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later.

Conclusions: We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue.

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


Environmental factors in inflammatory bowel disease: a co-twin control study of a  Swedish-Danish twin population

Abstract:
Background: Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method. SUBJECTS AND

Methods: A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups.

Results: The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1).

Conclusions: The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.


Knowledge, attitude and practice of natural family planning methods in a  population with poor utilisation of modern contraceptives

Abstract: Sub-Saharan Africa has one of the highest fertility rates in the world, which is further promoted by the low utilisation of modern contraceptive methods. Yet, many communities claim to have traditional methods of family planning that pre-date the introduction of modern contraceptives, implying that contraception is a culturally acceptable norm. It was therefore postulated that the study population would have a high level of awareness and practice of natural methods of family planning. We aimed to obtain an insight into the extent and correctness of knowledge about natural family planning methods, and its practice as a guide to the general acceptance of contraception as a concept. Pre-tested structured questionnaires were administered to women of childbearing age in households properly numbered for primary healthcare activities. The level of awareness of natural family planning methods was significantly less than awareness for modern methods of contraception. The awareness rate for rhythm method, lactational amenorrhoea method and coitus interruptus was 50.7%, 42.1% and 36.1%, respectively. For all three national family planning methods, there is a steady decline between awareness, correct description of method and utilisation, a difference that was statistically significant in all cases. The sociodemographic factors of the responders had varying influence on utilisation of all three natural family planning methods studied. Rural dwellers practised the lactational amenorrhoea method significantly more often than urban dwellers. Significantly more Muslims than Christians with four children or more practised coitus interruptus or the rhythm method, while the use of lactational amenorrhoea method was significantly increased with the number of living children in both religious groups. There is a relatively low level of awareness of natural family planning methods in the study population, poor utilisation and wrong use of methods. Therefore, improving the correct level of information on natural family planning methods is likely to improve the use of both natural family planning and modern contraceptive methods.

Journal of Obstetrics and Gynaecology : the Journal of the Institute of  Obstetrics and Gynaecology


Survey of attitudes regarding natural family planning in an urban Hispanic  population

Clinton J Leonard

Department of Obstetrics, Gynecology and Women's Health, Phoenix, AZ 85008, USA.

Abstract:
Methods: We performed a cross-sectional survey of 357 reproductive-aged women, mostly Hispanic (81.8%), presenting for ambulatory and hospital reproductive care in Phoenix, AZ, about their interest in natural family planning (NFP). Participants completed questionnaires, and responses were analyzed to determine predictors of interest in NFP.

Results: Sixty-one percent stated that they were likely or very likely to use NFP to avoid pregnancy, and 50% would use NFP to achieve pregnancy. Of factors studied, Hispanic ethnicity, lower level of acculturation, less education and recent use of condoms or withdrawal were independently associated with interest in using NFP to avoid pregnancy. Younger age and desire for future pregnancy were independently predictive of potential NFP use to achieve pregnancy.

Conclusion: This study suggests that Hispanic women find NFP to be an appealing family planning alternative.


Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Abstract: Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10(-12)-10(-3) M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor RORalpha by RT-PCR. Melatonin at pharmacological concentrations (10(-3)-10(-7) M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10(-12)-10(-10) M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor RORalpha including its isoform RORalpha4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.


Melatonin induces apoptosis in human neuroblastoma cancer cells

Abstract: Low concentrations (nanomolar) of melatonin had been previously shown to inhibit cell proliferation in several cancer cell lines as well as in experimental animal models. Additionally, cell growth inhibition and differentiation of prostate cancer cell lines by high concentrations (micromolar to millimolar) of melatonin have been recently reported. In the present paper, we show the induction of apoptosis by high doses of melatonin in the human neuroblastoma cell line SK-N-MC. We found accumulation of cells in the G2/M cell cycle phase and induction of cellular death, measured as lactate dehydrogenase (LDH) released into the culture medium, under millimolar concentration of melatonin. Apoptosis was evaluated using 4,6-diamidino-2-phenylindole staining, DNA gel electrophoresis, electron microscopy, and annexin V binding. Apoptosis progressed through the classical pathway, which involves caspase-3 activation. Cell death was dose and time-dependent; the lowest effective concentration of melatonin was 100 microm. Treatment with 1 mm melatonin for 6 days induced cell death in 75% of the cells. This novel finding shows that a nontoxic natural indoleamine may be potential therapy for some types of human neuroblastomas.


Normalization of hyperinsulinemia by chronic opioid receptor blockade in hyperandrogenemic women

Abstract: OBJECTIVE: Evaluation of the effects of naltrexone on hyperinsulinemia and hyperandrogenemia in hyperandrogenemic, hyperinsulinemic women. DESIGN: Controlled clinical study. SETTING: Department of Gynecologic Endocrinology and Reproductive Medicine, Center of Obstetrics and Gynecology, Medical University of Innsbruck, Austria. PATIENT(S): Thirty-nine hyperandrogenemic, hyperinsulinemic women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/d) for >or=3 weeks. MAIN OUTCOME MEASURE(S): Body mass index (BMI), gonadotropin (LH, FSH) and androgen (T, free T, DHEAS) levels, and plasma levels of glucose, insulin, and C-peptide, during a standard 75-g oral glucose tolerance test (OGTT), were determined before and during chronic opiate receptor blockade. RESULT(S): The BMI did not change during therapy. When OGTT was repeated after treatment with naltrexone, glucose levels were not different from those before treatment. Insulin response, however, had dramatically declined. We also observed a significant decrease in the levels of serum androgens. CONCLUSION(S): Hyperinsulinemia associated with hyperandrogenemia can be improved or completely abolished by chronic opiate receptor blockade. This observation suggests that endogenous opiates play a critical role in the process leading to hyperinsulinemia in hyperandrogenemia.


Reduced fertility among overweight and obese men

D D Baird

Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA

Abstract:
BACKGROUND: Overweight and obese men have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility.

METHODS: We examined the relationship between male body mass index (BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife <40 years old) with an attempt at pregnancy in the last 4 years based on pregnancy and fertility data provided by wives. Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression.

RESULTS: Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01-1.25; n = 1329). There was a dose-response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association.

CONCLUSIONS: This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment.


17alpha-hydroxyprogesterone caproate for the prevention of preterm delivery: A cost-effectiveness analysis

Abstract: OBJECTIVE: To evaluate whether the use of 17alpha-hydroxyprogesterone caproate for the prevention of recurrent preterm deliveries is cost-effective. METHODS: Using decision-analysis modeling, we compared the cost-effectiveness of using 17alpha-hydroxyprogesterone caproate in four subgroups: 1) Prior preterm deliveries less than 32 weeks; 2) prior preterm deliveries 32-37 weeks; 3) prior term delivery; and 4) no prior delivery. Each subgroup was compared with a "no treatment" group. Costs included those for 17alpha-hydroxyprogesterone caproate, hospital admissions, and complications from preterm deliveries. The main outcome measures include cost per quality-adjusted life-year gained and the number of preterm deliveries prevented. Secondary outcomes include neonatal complications prevented. One-way and multiway sensitivity analyses were performed. RESULTS: The use of 17alpha-hydroxyprogesterone caproate for the prevention of preterm deliveries result in cost-savings in women with prior preterm deliveries less than 32 weeks and 32-37 weeks. The sensitivity analyses revealed the model to be robust over a wide range of values for evaluated variables. CONCLUSION: Within our baseline assumptions, 17alpha-hydroxyprogesterone caproate was associated with cost-savings when used for the prevention of preterm deliveries in women with prior preterm deliveries.


Hormone-related risk factors for breast cancer in women under age 50 years by  estrogen and progesterone receptor status: results from a case-control and a  case-case comparison

Leslie Bernstein

Centers for Disease Control and Prevention

Giske Ursin

Division of Cancer Etiology, Department of Population Sciences, City of Hope Medical Center, Duarte, California; Departments of 2Preventive Medicine and 3Pathology, Keck School of Medicine, Univers...

Abstract:
Introduction: It has been suggested that hormonal risk factors act predominantly on estrogen receptor and progesterone receptor (ER/PR)-positive breast cancers. However, the data have been inconsistent, especially in younger women.

Methods: We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients. We used multivariable unconditional logistic regression methods to conduct case-control comparisons overall as well as by


Overt and 'subclinical' hypothyroidism in women

Douglas Van Nostrand

Uniformed Services University of the Health Sciences

Abstract:
Thyroid disease in general, and hypothyroidism in particular, are very common in women. In the USA, the most common cause of primary thyroid deficiency is on an autoimmune basis due to lymphocytic (Hashimoto) thyroiditis. Because there are thyroid hormone receptors in virtually every tissue of the body, the manifestations of hypothyroidism are varied, but problems with abnormal menses, conception, fertility, and pregnancy can be especially troubling in young women. The single most important diagnostic test is measurement of serum thyrotropin (TSH). The overwhelming majority of patients with hypothyroidism are treated with a single daily dose of synthetic levothyroxine with the goal of therapy being restoration of a normal metabolic state with return of the TSH level down to the range of 0.5 to 1.5 mlU/L. "Subclinical" hypothyroidism refers to those patients with early or mild thyroid hypofunction manifested as slight elevations of thyrotropin (approximately 4-10 mlU/L) although serum thyroxine (T4) and triiodothyronine (T3) levels are within their reference ranges. The entity is somewhat controversial in regard to its consequences if left untreated, and whether or not we should be screening patients, at least susceptible populations, for the condition. Reports indicate an association between subclinical hypothyroidism and poor outcomes of pregnancy, as well as dyslipidemias, atherogenesis, and increased mortality in the long term. We believe these consequences are sufficiently compelling to warrant screening and treatment with levothyroxine when found to halt progression to overt hypothyroidism, and improve symptoms, pregnancy outcomes, lipid abnormalities, and cardiovascular function. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.

LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that hypothyroidism is a common disease in women, has many protean manifestations, and can be successfully diagnosed and treated; explain that the condition of subclinical hypothyroidism can be diagnosed and if treated can prevent many untoward complications; and state that there should be heightened awareness of the disease so that proper screening tests can be performed.


Fertility awareness-based methods of family planning: predictors of correct use

Abstract:
Context: Fertility awareness-based methods of family planning help women identify the days of the menstrual cycle when they are most likely to become pregnant. To prevent pregnancy, women avoid unprotected intercourse on these days. Efficacy of these methods may be improved if the users most likely to engage in unprotected intercourse on fertile days can be identified and counseled.

Methods: Quantitative and qualitative data from efficacy studies of the Standard Days Method and the TwoDay Method of family planning, in which 928 women each contributed up to 13 cycles of method use, were examined. Multinomial logit analysis was used to compare characteristics of women who occasionally had unprotected intercourse on fertile days with those who consistently used their method correctly. The reasons participants gave for having unprotected intercourse on fertile days were also examined.

Results: Only 23% of women had unprotected intercourse on their fertile days in one or more of the cycles they contributed to the study. The method and study site appear to have the most significant effect on correct use. Earning an income was associated with increased odds of unprotected intercourse on fertile days; higher quality of housing was associated with decreased odds. The results confirm the importance of partner cooperation for correct method use.

Conclusion: There was no clear profile of clients for whom these family planning methods would be inappropriate. However, programs offering these methods may help couples overcome potential difficulties in correct method use by including male partners and encouraging their participation in counseling sessions.

International Family Planning Perspectives


The biology of human sex differences

The biology of human sex differences

Abstract: To the Editor: In the discussion of biologic differences between male and female fertility (April 6 issue),1 Federman states that women are fertile for only 12 hours each month. Although the egg is viable for 12 hours or less, the window of fertility in women is approximately five to six days in each menstrual cycle,24 depending on the presence of estrogenic cervical mucus that maximizes the storage, survival, and transport of sperm until ovulation.4,5 Dr. Federman replies: Stanford rightly calls attention to the elegant estrogen-dominated events that precede ovulation and that favor passage of sperm through the cervix . . .


The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from the Canadian Multicentre Osteoporosis Study

Canadian Multicentre Osteoporosis Study Group

For the Canadian Multicentre Osteoporosis Study (CaMos)

Abstract:
Introduction: The use of cyclooxygenase-2 (COX-2) inhibitors has been demonstrated to not only impair load-induced bone formation but also prevent menopause-associated bone loss. We hypothesized that COX-2 inhibitor use would be associated with increased bone mineral density (BMD) in postmenopausal women not using estrogen therapy and, conversely, with decreased BMD in men.

Methods: The Canadian Multicentre Osteoporosis Study is a longitudinal, randomly selected, population-based community cohort. We present data from men (n=2,004) and postmenopausal women age 65 and older (n=2,776) who underwent a BMD measurement and structured interview in the 5th year of the study. The outcome measure was percent difference in BMD (g/cm(2)).

Results: Daily COX-2 inhibitor use was reported by 394 subjects. In men, daily use of COX-2 inhibitors was associated with a lower BMD at all hip sites, with a percent difference of -3.1% [95% confidence interval (CI), -6.0, -0.3] between users and nonusers at total hip. In postmenopausal women not using estrogen replacement therapy, daily COX-2 inhibitor use was associated with higher BMD at most sites [percent difference at total hip: +3.0% (95% CI, 0.3, 5.8)]. These effects appeared to be dose-dependent.

Conclusion: COX-2 inhibitor use was associated with a lower BMD in men and, on the other hand, with a higher BMD in postmenopausal women not using estrogen replacement therapy. Men who have used COX-2 inhibitors may wish to seek BMD measurement to assess their fracture risk. However, COX-2 inhibitors may have utility in postmenopausal women if bone-selective analogs can be developed.


Usefulness of monitoring fertility from menarche

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: The concept of the ovarian cycle as a continuum considers that all types of ovarian activity encountered during the reproductive life are responses to different environmental conditions in order to ensure the health of the woman. During the normal ovulatory cycle, a series of sequential events have to occur in a highly synchronized manner. Fertility awareness is useful in helping women to identify the different stages of their reproductive life cycle. Fertility awareness is also a valuable tool in helping women to identify gynecological disorders. Persistence of irregularities within the mucus patterns and the menstrual cycle should be of concern to women presenting with these problems. These irregularities may be due to obstetrical, endocrine, gynecological or iatrogenic disorders. Insight into early pregnancy complications, ovulatory dysfunction and pelvic inflammatory disease can be ascertained from abnormalities within the menstrual cycle and mucus pattern. Thus, fertility awareness will also enable the recognition and early treatment of several metabolic, endocrine and infectious diseases.

Journal of Pediatric and Adolescent Gynecology


Variability in the phases of the menstrual cycle

Abstract:
Objective: To determine variability in the phases of the menstrual cycle among healthy, regularly cycling women.
Design: A prospective descriptive study of a new data set with biological markers to estimate parameters of the menstrual cycles.

Participants: One hundred forty one healthy women (mean age 29 years) who monitored 3 to 13 menstrual cycles with an electronic fertility monitor and produced 1,060 usable cycles of data. MEASURES AND

Outcomes: Variability in the length of the menstrual cycle and of the follicular, fertile, and luteal phases, and menses. The estimated day of ovulation and end of the fertile phase was the peak fertility reading on the monitor (i.e., the urinary luteinizing hormone surge).

Results: Mean total length was 28.9 days (SD = 3.4) with 95% of the cycles between 22 and 36 days. Intracycle variability of greater than 7 days was observed in 42.5% of the women. Ninety-five percent of the cycles had all 6 days of fertile phase between days 4 and 23, but only 25% of participants had all days of the fertile phase between days 10 and 17.

Conclusions: Among regularly cycling women, there is considerable normal variability in the phases of the menstrual cycle. The follicular phase contributes most to this variability.

Journal of Obstetric, Gynecologic, and Neonatal Nursing : JOGNN


Diagnosis and management of dysmenorrhoea


Unsuccessful attempt to demonstrate progesterone's bone formation actions

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Siri Forsmo

Norwegian University of Science and Technology

American journal of obstetrics and gynecology


The psychobiology and diagnostic significance of amenorrhea in patients with anorexia nervosa

J Jordan

Department of Obstetrics and Gynecology, University of Washington, Seattle.

Abstract: Amenorrhea is a diagnostic criterion for anorexia nervosa (AN), although menstrual cycles have been found to persist in some women with all the other features of AN. This study sought to determine factors that are associated with amenorrhea in 39 women with current primary spectrum AN. The use of exercise to control weight (odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.3-9.9; P = .02), low novelty seeking scores (OR = 0.7; 95% CI = 0.58-0.94; P = .02), and low systolic blood pressure (OR = 0.9; 95% CI = 0.84-0.99; P = .046) were predictors of amenorrhea independent of body mass index.


Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications

Haslinda Hassan

Raja Isteri Pengiran Anak Saleha Hospital

Gianni Formoso

Department of Endocrinology (R.N., G.F.), Azienda Ospedaliera LE/1, 73100 Lecce, Italy

Abstract:
CONTEXT: Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications.

OBJECTIVE: We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects.

DESIGN: This was a prospective study.

SETTING: The study was conducted in the Department of Obstetrics and Gynecology.

PATIENTS: A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)).

INTERVENTION: TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group.

MAIN OUTCOME MEASURES: Rates of obstetrical complications in treated and untreated groups were measured.

RESULTS: At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7).

CONCLUSIONS: Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.

The Journal of Clinical Endocrinology and Metabolism


Cervical mucus symptom and daily fecundability: first results from a new  database

Bernardo Colombo

National Institute of Environmental Health Sciences

Abstract: With the collaboration of Italian centres providing services on natural family planning, a prospective study collected data on 2755 menstrual cycles of 193 women. A database was constructed using information on the daily characteristics of cervical mucus and episodes of intercourse. Taking the day of peak mucus as a conventional marker of ovulation, the database identified the length (12 days) and location of a 'window' of potential fertility, the highest level of conception probability being confined to the central five to six days. Univariate analysis provided evidence of the impact on fecundability of the woman's age and the basic infertile pattern of a cycle. Several analytical approaches highlighted the relationship between daily mucus characteristics and levels of fecundability


The origin of informed consent

The origin of informed consent

Abstract: The principle of informed consent, aimed at the lawfulness of health assistance, tends to reflect the concept of autonomy and of decisional autodetermination of the person requiring and requesting medical and/or surgical interventions. This legal formula, over the last few years, has gained not only considerable space but also importance in the doctrinal elaboration and approaches, as well as juridical interpretations, thereby influencing the everyday activities of the medical profession. Informed consent is still the object of continuous explorations, not only asfar as concerns the already confirmed theoretical profile but, instead, the ambiguous practical and consequential aspect. Analysing how the concept and role of consensus was born and developed with the more adequate and reasonable excursions to make it valid and obtain it, it is impossible not to take into consideration, on the one hand, the very ancient philosophical origins and, on the other, the fact that it was conditioned by religion with the moral aspects and the accelerated deontological evolution with pathways parallel to the needs and the progress offered by new forms of treatment and novel biotechnological applications. The principle of consent is a relatively new condition. In fact, already in the times of not only the Egyptian civilisation, but also the Greek and Roman, documents have been found which show how the doctor's intervention had, in some way, first to be approved by the patient. Plato (law IV) had already foreseen the problems, the procedures and the modes of information which are, in synthesis, at the root of the principles of the present formula of informed consent and correlated the practice of the information and consensus with the quality and social position of the patient. The only guarantee that the patient might have, derived from a fundamental principle of medicine of all times: "in disease, focus on two aims, to improve and not to cause damage". A figure can be recognised, in the Hippocratic physician, that cared about the patient's suffering, but never neglected looking after his own outcome, endeavouring to avoid becoming involved in lack of success and death of a patient. The concept of consensus is inexistent, albeit, there is an awareness of the presence of precautious and preventive information. In the behaviour of doctors, in ancient times, it is not difficult to recognize the true motives and the real reasons that, already in those days, give rise to the necessary "defensive medicine" particularly as far as concerns the social status of the patient. Already from the early origins, continuing the Hippocratic tradition, the relationship between doctor and patient was consolidated, based upon two very definite criteria, represented, on the one hand, by the professional duty of the physician to do what is bestfor the patient and, on the other, the duty of the patient to completely accept the physician's decisions and intervention. The Hippocratic physician respected a principle of professional responsibility which was more religious and of a moral type, but, from a legal point of view, very weak inasmuch as it depended upon regulations elaborated by human beings. The conviction and certainty that the physician acted, in the interest of his patient's well-being, has been passed down over the centuries endowing the physician with moral authority and a kind of legal impunity, conditions which corresponded, in an almost reflection-likefashion, with the duty of obedience and subjection, on the part of the patient. Christianity was grafted into this consolidated vision of the sacral character of medicine and medical practice, which did not substantially change the Hippocratic type of ethical behaviour. Non only the population but also the Christian physician was aware of the religious importance of his intense activity as a mission and compared to a special kind of priesthood in safe-guarding health, considered as a gift of God. Therefore, invested with this authority which derived from his professional role and from his very work, he felt it his duty to guide the patient, deciding and for him. The patient is an ignorant person who does not have the knowledge, the intellectual capacity or moral authority to oppose or disagree with the wishes and decisions of the physician who, instead, on account of his doctrine, knows exactly what is goodfor him. In this regard, if we were to speak of consensus concerning the physician's intervention, he would be considered useless in as much as obvious and understood when seeking help. The attitude of the patient towards the physician has always tended to one of strong faith and characterized by psychological subjection borne out by traditions thousands of years old. A patient who was sick, again, as an attitude of respect and gratitude, followed the treatment but never asked for any explanations regarding the therapeutic effects and the physician refrained from taking any initiative to inform the patient or his/her family. Each phenomenon, therefore, has a precise origin, a well-defined history and when its importance tends to significantly condition the activities concerning Man, a desire emerges to learn the origin and the history. As is well known, a trial commenced in Nuremberg, on December 19, 1946, of Nazi doctors and a code was defined in which the judges, all Americans, clearly emphasized a view of medical research and technology: science should never transform or consider human beings as an instrument to be employed for scientific purposes. In actual fact, documents exist providing evidence that a few decades before the drawing up of the Nuremberg Code, the need had been expressed, in Germany itself to somehow make medical interventions and actions legal by means of the use and practice of consensus. The moral and ethical principles in those documents, even if not available as bibliographic references in the English literature, certainly merit, from a historical viewpoint to be considered as conceptual elements and doctrinal and socio-cultural products, even if at that time, of little practical importance, which belong to the European culture and, in particular, and almost paradoxically, in the light of what happened, to the German culture. The United States of America is held to be the country of origin of informed consent, the initial aim of which was make sure that the correct dignity of the patient's independence be reserved at the time of decision making and choice of medical options. Reports on this topic, in fact, first appeared in the USA, at the beginning of the 18th Century, with problems focusing on and limited to only the simple rights of the patient in giving his/her approval of the health intervention later to be conceptually developed, along the lines of an itinerary with, at intervals, famous legal actions, until in the 20th Century, informed consent was reached, a criterion that, as is well known, foresees and includes not only the important and fundamental autonomy of the patient to decide, which stems ones personal rights, but also the essential objective element, which is, information. The expression informed consent has simply been transposed in Italian and roughly translated in an ambiguous fashion into "consenso informato" when, on the contrary, it should be referred to as "informazione per il consenso" "information for consensus" not only to respect the concept but, surely, for a more correct deciphering and a more precise interpretation related to the numerous concepts it presupposes and implies. Information and consent may be compared to the two sides of the same coin. These are the two important pillars that coincide and are joined giving weight to the medical responsibility, as far as concerns consent to the health intervention: on the one hand, having obtained consent,following correct and sincere information interpreted and deciphered as an important phase and an essential indicator of correct, scrupulous medico-professional procedure and, on the other, the consensus itself conceived as a duty aiming at the maximum respect of the rights to autodetermination, independence and autonomy of the patient, as a person. At the beginning of the Nineties, as we have seen, we were made aware of a series of legal actions regarding medical responsibility which was greatly conditioned by the Anglosaxon influence which initially induced many Italian magistrates and forensic physicians to adopt an extremely rigid attitude with no attempt to comply, in any way, with the culture and traditions of our country and our tradition which has always been inspired by good common sense, both medical and human. The American experience has been very rapidly adopted, by some, without a profound, complete and necessary historical and evolutional analysis aimed at those intertwined principles that have been motifs that have gradually led to the legal references in those emblematic cases referred to, the conclusions of which continue to attract a great deal of attention. In Italy, the legal and doctrinal evolution of informed consent, even if following a little more rapidly the traces, steps, problems and interpretations of the various aspects drawn up, characterized and applied in the United States, has not only occurred at a later time, but, despite reaching the same meaningful objectives, the same considerations, the same importance, and, unfortunately, the same inconveniences, has had quite different aims, approaches and articulations. In this respect, it is enough to focus attention on the different cultural traditions and religious routes, on the different doctrinal background, the particular historical origins and the individual legal aspects, all extremely different one from the other. (ABSTRACT TRUNCATED)

Acta Otorhinolaryngologica Italica : Organo Ufficiale Della Societa Italiana Di  Otorinolaringologia E Chirurgia Cervico-facciale


Sperm integrity pre- and post-chemotherapy in men with testicular germ cell  cancer

J R Spermon

Department of Urology, Radboud University Nijmegen Medical Centre, The Netherlands. spermon@hotmail.com

Abstract:
Background: While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood.

Methods: Semen and serum from 22 patients treated for testicular cancer were analysed preand post-chemotherapy. Besides routine semen analysis, sperm samples were evaluated by computerized karyometric image analysis (CKIA), chromomycin-A3 assay (CMA3, chromatin condensation) and TdT-mediated dUTP nick-end labelling assay (TUNEL, DNA damage). Serum FSH, LH and testosterone concentrations were measured.

Results: Ejaculate volume decreased post-chemotherapy (P<0.05). External sperm characteristics (CKIA morphometry) and sperm counts did not deteriorate after chemotherapy. An improvement in DNA condensation was assessed after chemotherapy (37 versus 50% and 47.5 versus 63.7% for CMA3 and CKIA respectively; both P<0.005); yet a high percentage of TUNEL-positive sperm was found in the samples (21 versus 25% for preand post-chemotherapy samples respectively). These values were significantly higher than those of a convenience sample of normozoospermic males attending pre-IVF screening. Serum FSH and LH (IU/l) increased after chemotherapy compared with pretreatment levels (8.1 versus 16.7 and 4.5 vs 6.8; both P<0.05, respectively).

Conclusions: Despite the improvement in sperm chromatin packaging after chemotherapy, an abnormally high percentage of DNA-damaged sperm was found in these samples. As sperm quality does not reach normal levels after treatment, it remains difficult to outline the best strategy and guidance concerning fertility potential of testicular cancer patients.


Comparison of assisted reproductive technology utilization and outcomes between Caucasian and African American patients in an equal-access-to-care setting

Eve C. Feinberg

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.

Abstract:
OBJECTIVE: Racial disparity in assisted reproductive technology (ART) outcomes has been reported but remains controversial. Reasons for the disparity are unclear, and access to care has been suggested as a causative factor. In this study, we sought to examine minority utilization of ART in the Department of Defense (DoD) compared with minority utilization in the U.S. ART population. Outcomes from ART were compared between Caucasian (Cau) and African American (AA) patients, and etiologies of disparity were examined.

DESIGN: Retrospective cohort study.

SETTING: University-based ART program.

PATIENT(S): A total of 1,457 patients undergoing first-cycle fresh, nondonor ART.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate, implantation rate, spontaneous abortion rate.

RESULT(S): Within the DoD population, AA women had a fourfold increase in utilization of ART services relative to the U.S. ART population. In this equal-access-to-care setting, AA women experienced a clinically significant decrease in live birth rate that did not reach statistical significance (29.6% vs. 35.8%, risk ratio [RR] 0.83, 95% confidence interval [CI] 0.67-1.02) and a statistically significant increase in spontaneous abortions compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be explained, in part, by a higher prevalence of uterine leiomyomas in AA women (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women, the presence of fibroids at baseline ultrasound was associated with reductions in clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR 0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%, RR 0.63, 95% CI 0.44-0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98).

CONCLUSION(S): Utilization of ART services among AA women increased when access to care was improved. A clinically significant reduction in live birth rate and statistically significant increase in spontaneous abortion rate was observed in AA women compared with Cau women. Leiomyomas were three times more prevalent in AA women and reduced ART success, regardless of race. The persistence of racial differences in an equal-access-to-care environment might be explained, in part, by the increased prevalence of leiomyomas in AA women.


The reproductive significance of human Fallopian tube cilia

R A Lyons

Academic Department of Obstetrics and Gynaecology, St. Bartholomew's and The Royal London Hospital School of Medicine and Dentistry, Whitechapel, London E1 1BB, UK.

Abstract: Effective tubal transport of ova, sperm and embryos is a prerequisite for successful spontaneous pregnancy. Although there is much yet to be discovered about the mechanisms involved, it is evident that tubal transit is a far more complicated process than initially thought. Propulsion of gametes and embryos is achieved by complex interaction between muscle contractions, ciliary activity and the flow of tubal secretions. Evidence is accumulating of the important and possibly pre-eminent role of ciliary motion in this process; and this review describes current knowledge about ciliary activity and its physiological regulation. There is also a description of the effects on ciliary function of cigarette smoking and various pathological states, including endometriosis and microbial infection, with consideration given as to how altered ciliary activity may impact upon fertility.


The natural progression of health-related quality of life: results of a five-year  prospective study of SF-36 scores in a normative population

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract:
Background: Limited information exists regarding the natural progression of health-related quality of life (HRQOL) in the general population, as most research has been cross-sectional or has followed populations with specific medical conditions. Such norms are important to establish, because the effect of any intervention may be confounded by changes due to the natural progression of HRQOL over time.

Methods: Participants were randomly selected from 9 Canadian cities and surrounding rural areas. Changes in the eight domains and 2 summary component scores of the Medical Outcomes Study 36-item short form (SF-36) were examined over a 5 year period (1996/1997-2001/2002). Mean changes were calculated for men and women within 10 year age categories. Multiple imputation was used to adjust for potential selection bias due to missing data.

Results: The baseline sample included 6539 women and 2884 men. Loss to follow-up was 17% for women and 23% for men. Mean changes tended to be small, but there was an overall trend towards decreasing HRQOL over time. Changes were more pronounced in the older age groups and in the physically oriented domains. Younger age groups tended towards small mean improvements, particularly in the mentally oriented domains. Large standard errors suggest that on an individual level, large improvements in some participants are balanced by large declines in others.

Conclusion: In general, the HRQOL of Canadians appears relatively stable over a 5 year period. However, care should be taken when assessing HRQOL longitudinally in certain age or gender groups, as changes associated with an intervention can potentially be confounded by the natural progression of HRQOL.

Quality of Life Research : an International Journal of Quality of Life Aspects of  Treatment, Care and Rehabilitation


Oral contraceptive use and risk of fractures

Abstract:
Introduction: Prior studies have suggested that oral contraceptives (OCs) may be associated with an increased fracture risk. However, the previous studies have only performed a limited adjustment for other potential risk factors.

Subjects and methodsAll women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was use of OCs between January 1, 1996, and December 31, 2000. Adjustments were made for use of other drugs, pregnancy, prior fracture, other diseases and social variables.

Results: In the unadjusted analysis, use of OCs in low dose was associated with a small increase in overall fracture risk. However, upon adjustment, no increase in fracture risk could be demonstrated in any age or dose group.

Conclusion: Oral contraceptives are not associated with an increase or a decrease in fracture risk. Any change in fracture risk may be due to confounders.


Effect of short-term and long-term treatments with three ecotypes of Lepidium meyenii (MACA) on spermatogenesis in rats

Abstract: Lepidium meyenii (Brassicaceae), known as Maca, is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m above sea level in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The study aimed to test the hypothesis that different ecotypes of Maca (Red, Yellow and Black) after short-term (7 days) and long-term (42 days) treatment affects differentially spermatogenesis adult rats. After 7 days of treatment with Yellow and Red Maca, the length of stage VIII was increased (P<0.05), whereas with Black Maca stages II-VI and VIII were increased (P<0.05). Daily sperm production (DSP) was increased in the group treated with Black Maca compared with control values (P<0.05). Red or Yellow Maca did not alter DSP and epididymal sperm motility was not affected by treatment with any ecotype of Maca. After 42 days of treatment, Black Maca was the only ecotype that enhanced DSP (P<0.05). Moreover, Black Maca was the only that increased epididymal sperm motility (P<0.05). In relation to the control group, Red Maca did not affect testicular and epididymal weight nor epididymal sperm motility and sperm count; however, prostate weight was reduced (P<0.05). Black or Yellow Maca did not affect prostate weight. In conclusion, there were differences in the biological response of the three ecotypes of Maca (Yellow, Red and Black). Black Maca appeared to have more beneficial effect on sperm counts and epididymal sperm motility.


Progestogen-only contraception and bone mineral density: a systematic review

Kathryn M Curtis

Centers for Disease Control and Prevention

Abstract: Questions have been raised about the effects of progestogen-only contraceptive use on bone health, particularly among young women who have not yet reached peak bone mass and perimenopausal women who may be starting to lose bone mass. We conducted a systematic review that evaluated the association between progestogen-only contraceptive use and fracture risk or bone mineral density (BMD). We identified 39 articles from MEDLINE and EMBASE, published through July 2005. One study reported that depot medroxyprogesterone acetate (DMPA) users were more likely to experience stress fractures than nonusers; this association was not statistically significant after controlling for baseline bone density. In cross-sectional studies, the mean BMD in DMPA users was usually below that of nonusers, but within 1 SD. In longitudinal studies, BMD generally decreased more over time among DMPA users than among nonusers, but women gained BMD upon discontinuation of DMPA. Limited evidence suggested that use of progestogen-only contraceptives other than DMPA did not affect BMD.


Preventing copper intrauterine device removals due to side effects among  first-time users: randomized trial to study the effect of prophylactic ibuprofen

Abstract:
Background: Increased menstrual bleeding and pain are the primary side effects that lead to early removal of the copper intrauterine device (IUD). Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) are proven treatments for such IUD-induced problems, but their effect on early IUD removal is unknown.

Methods: A total of 2019 first-time IUD users were recruited in Chile for this double-blind, randomized, placebo-controlled trial. Half of the participants were given ibuprofen and instructions to take 1200 mg daily during menses (for up to 5 days each cycle) for the first 6 months of IUD use. The other half were asked to take an identical appearing placebo in the same manner. The primary outcome was IUD removal within 12 months of insertion.

Results: A total of 1011 and 1008 women were randomly assigned to ibuprofen and placebo, respectively. During 12 months of observation, 190 had the device removed because of dysmenorrhoea and/or increased menstrual bleeding: 85 in the placebo group and 105 in the ibuprofen group. For ibuprofen users, the hazard ratio for removal for these IUD-induced side effects was 1.0 and 1.2 at 6 and 12 months, respectively (both not significant).

Conclusion: Although increased menstrual bleeding and pain are common reasons for early IUD removal, prophylactic use of ibuprofen, at the dosage used here, does not reduce removal rates.