The metabolic syndrome and male infertility

Sanjay S Kasturi

Department of Urology, Northwestern University Feinberg School of Medicine, 303 East Chicago Ave, Tarry16-703, Chicago, IL 60611, USA.

Abstract: Metabolic syndrome (MetS) is highly prevalent, affecting more than 47 million US residents. This condition is also multifaceted, potentially leading to significant disturbance of numerous physiologic processes. This review article evaluates the literature regarding metabolic syndrome and male reproductive health. Links between obesity, dyslipidemia, hypertension, and insulin resistance are each examined with regard to their associated detrimental effects on male fertility. At the end of this manuscript, we propose a new MetS/male infertility paradigm. Additional studies specifically addressing the components of MetS and their impact on male reproduction will enhance our understanding of the underlying pathophysiology. These studies may also help clarify the role for therapeutic intervention.


Dual-Energy X-Ray Absorptiometry Technical issues: the 2007 ISCD Official Positions

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: At the 2007 Position Development Conference, the Dual-Energy X-ray Absorptiometry Technical Task Force investigated three major areas of bone density testing. Although bone mineral density (BMD) testing in men had previously been reviewed at the 2005 Position Development Conference, we reviewed the most recent data in men to develop appropriate indications for bone density testing in men. We continue to recommend screening at age 70 and discuss the clinical risk factors that may be an appropriate indication for earlier BMD testing. Menopausal transition (perimenopause) was considered an important time to consider BMD evaluation because bone loss may be significant prior to menopause. However, because fracture risk is inherently low in women of this age without other risk factors, screening BMD testing is not appropriate. We discuss the risk factors that are strong indicators of fracture risk that may be increased during the menopause transition. The presence of these risk factors are appropriate indications for BMD testing with applicability of WHO diagnostic categorization. The issue of establishing a high threshold for BMD was investigated thoroughly and the current literature was reviewed. Despite the fact there is agreement that all BMD values greater than T-score -1.0 are not normal, it was felt that because of the paucity of sensitivity data and confounding factors such as high body mass index, an upper threshold could not be established or recommended at this time. This was felt to be an important area for further research.


Emergency contraception: overestimated effectiveness and questionable expectations


The Medical and Surgical Practice of NaProTechnology, by Thomas W. Hilgers, M.D

The national Catholic bioethics quarterly


DIR Jahrbuch 2007 (Deutsches IVF-Register Annual Report 2007)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2007. 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).


Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study

Abstract:
OBJECTIVE: To investigate the effect of cell phone use on various markers of semen quality.

DESIGN: Observational study.

SETTING: Infertility clinic.

PATIENT(S): Three hundred sixty-one men undergoing infertility evaluation were divided into four groups according to their active cell phone use: group A: no use; group B: <2 h/day; group C: 2-4 h/day; and group D: >4 h/day.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Sperm parameters (volume, liquefaction time, pH, viscosity, sperm count, motility, viability, and morphology).

RESULT(S): The comparisons of mean sperm count, motility, viability, and normal morphology among four different cell phone user groups were statistically significant. Mean sperm motility, viability, and normal morphology were significantly different in cell phone user groups within two sperm count groups. The laboratory values of the above four sperm parameters decreased in all four cell phone user groups as the duration of daily exposure to cell phones increased.

CONCLUSION(S): Use of cell phones decrease the semen quality in men by decreasing the sperm count, motility, viability, and normal morphology. The decrease in sperm parameters was dependent on the duration of daily exposure to cell phones and independent of the initial semen quality.


Infertility surgery is dead: only the obituary remains?

Eve C. Feinberg

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

Alan H DeCherney

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract: Despite the multiple advantages of assisted reproductive technology compared with surgery, there remain several diagnoses for which surgery is still widely performed: distal tubal occlusion, regret of permanent sterilization, and endometriosis. Assisted reproductive technology is superior to surgery and should be offered as first-line treatment.


Cultural perceptions and practices around menarche and adolescent menstruation in the United States

Abstract: This overview details the persistence of negative characterizations of the menstrual cycle as a feature of the current cultural context in which girls begin menstrual life in the United States. In addition, research on girls' current menstrual attitudes and experiences within this context are reviewed. Current research suggests that girls are not very knowledgeable about menstruation, and that menstrual education continues to provide girls with mixed messages, such as: menstruation is a normal, natural event, but it should be hidden. Girls' attitudes and expectations about menstruation are negatively biased and have been found to contribute to self-objectification, body shame, and lack of agency in sexual decision-making. Although preparation has been found to be associated with more positive menarcheal and menstrual experiences, specificity about what constitutes "good" preparation has not been well articulated. Implications for promoting the menstrual cycle among young girls as a vital sign in service of monitoring their health are discussed.

Annals of the New York Academy of Sciences


Prevalence of premenstrual syndrome in autism: a prospective observer-rated study

Abstract: A systematic, prospective observer-rated study was carried out to determine the prevalence of late luteal phase dysphoric disorder (premenstrual syndrome) in women with autism. A group of women with autism and learning disability (n = 26) was compared with a group of women with a non-autism learning disability (n = 36) matched for age, in-patient status, intelligence, marital status, parity, behavioural problems and ethnicity. Observers rated DSM-IV symptoms of late luteal phase dysphoric disorder every day from each subject over three consecutive menstrual cycles. Using a premenstrual increase in DSM-IV symptoms of >or= 30% as evidence of fulfilment of diagnostic criteria, the prevalence of late luteal phase dysphoric disorder was 92% in the autism group compared with 11% in the control group. This difference was highly statistically significant. The principal conclusion from this study is that there is a marked increase in premenstrual syndrome in women with autism compared with matched controls.

The Journal of international medical research


Sperm Transport and Capacitation

Sperm Transport and Capacitation

Abstract: It is well understood that a myriad of complex steps occur between the time of ejaculation and the union of the haploid number of chromosomes from each partner that results in the final process of fertilization. Consequently, it is easy to imagine the numerous potential problems that can occur at each step, and thus may prevent a successful pregnancy. Often overlooked are the complexities of sperm transport and the steps that must occur in the sperm, a process known as capacitation, before fertilization can occur. These processes of sperm delivery and potentiation are addressed in detail in this chapter.


Effect of oral contraceptives on risk of cervical cancer

Abstract:
Objective: To assess the risk of oral contraceptives on the occurrence of cervical cancer. Material and Method: A hospital-based case-control study was conducted. Sixty women patients with histologically confirmed invasive cervical cancer and 180 healthy women as the control group who attended the King Chulalongkorn Memorial Hospital, Bangkok, Thailand were recruited. Information about the use of oral contraceptives and other cervical cancer risk factors were obtained from personal interviews. The risk factors were evaluated by using odds ratio (OR).

Results: 60 women with invasive cervical cancer and 180 healthy controls were interviewed by the investigators. Compared with non-users, patients who had ever used or currently used oral contraceptive had an increased risk of cervical cancer (OR 1.45; 95% CI 0.79-2.64). However the risk was not statistically significant. Considering the duration of use, patients who had used oral contraceptives for 3 years or less did not have an increased risk of cervical cancer (OR 0.78; 95% CI 0.39-1.77). Nevertheless, the odds ratio of oral contraceptive pill use for more than 3 years was 2.57 (95% CI 1.22-5.49) which was statistically significant.

Conclusion: Long-term use of oral contraceptive might be a cofactor that increases the risk of cervical carcinoma. Further investigations should be conducted to confirm this risk. However, Pap smear has to be done routinely in long-term oral pill users.


Oxidative stress and male infertility--a clinical perspective

Abstract: Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.


The pathophysiology of amenorrhea in the adolescent

Abstract: Menstrual irregularity is a common occurrence during adolescence, especially within the first 2-3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen-deficient or estrogen-replete. Estrogen-deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen-replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise-induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.


Obstetric Outcomes and Congenital Abnormalities After In Vitro Maturation, In Vitro Fertilization, and Intracytoplasmic Sperm Injection

Yearbook of Neonatal and Perinatal Medicine


Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion

Abstract: This study investigated whether progesterone administration modulates toll-like receptors (TLRs) and the nuclear factor-kappa B (NF-kappaB) signaling pathway in the injured rat brain following traumatic brain injury (TBI). Right parietal cortical contusion was made by a weight-dropping method. Male rats were given 0 or 16 mg/kg injections of progesterone at postinjury hr 1 and 6 and on days 1, 2, 3, 4, and 5. Brain samples were extracted at 5 days after trauma. We measured mRNA expression of TLR2 and TLR4 by reverse-transcriptase polymerase chain reaction (RT-PCR), NF-kappaB binding activity by electrophoretic mobility shift assay (EMSA), concentrations of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), intercellular adhesion molecule-1 (ICAM-1) expression by immunohistochemistry, and brain damage by TUNEL. The results showed that TBI induces strong up-regulation of TLR2, TLR4, NF-kappaB, pro-inflammatory cytokines, and ICAM-1 in the pericontusional area. Administration of progesterone following TBI down-regulates the cortical levels of these agents related to the TLRs/NF-kappaB signaling pathway. After progesterone administration, apoptotic TUNEL-positive cells in the injured brain were significantly decreased. In summary, post-TBI progesterone administration attenuates the TLRs/NF-kappaB signaling pathway in injured rat brain, and this may be a mechanism whereby progesterone improves the outcome following TBI.

Annals of Clinical and Laboratory Science


Veerle Goossens

Abstract: 14. Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE. Andersen AN(1), Goossens V, Ferraretti AP, Bhattacharya S, Felberbaum R, de Mouzon J, Nygren KG; European IVF-monitoring (EIM) Consortium; European Society of Human Reproduction and Embryology (ESHRE). (1)ESHRE Central Office, Meerstraat 60, B-1852 Grimbergen, Belgium. anyboea@rh.dk BACKGROUND: European results of assisted reproductive techniques from treatments initiated during 2004 are presented in this eighth report. METHODS: Data were mainly collected from existing national registers. From 29 countries, 785 clinics reported 367,066 treatment cycles including: IVF (114,672), ICSI (167,192), frozen embryo replacement (FER, 71,997), egg donation (ED, 10 334), preimplantation genetic diagnosis/screening (PGD/PGS, 2701) and in vitro maturation (IVM, 170). Overall, this represents only a marginal increase since 2003, due to a huge reduction in treatments in Germany. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 20 countries. A total of 115,980 cycles (IUI-H, 98,388; IUI-D, 17,592) were included. RESULTS: In 14 countries where all clinics reported to the IVF register, a total of 248,937 ART cycles were performed in a population of 261.6 million, corresponding to 1095 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.6% and 30.1%, respectively. For ICSI, the corresponding rates were 27.1% and 29.8%. After IUI-H, the clinical pregnancy rate was 12.6% in women below 40. After IVF and ICSI, the distribution of transfer of 1, 2, 3 and 4 or more embryos was 19.2%, 55.3%, 22.1% and 3.3%, respectively. Compared with 2003, fewer embryos were transferred, but huge differences still existed between countries. The distribution of singleton, twin and triplet deliveries after IVF and ICSI combined was 77.2%, 21.7% and 1.0%, respectively. This gives a total multiple delivery rate of 22.7% compared with 23.1% in 2003 and 24.5% in 2002. After IUI-H in women below 40 years of age, 11.9% were twin and 1.3% triplet gestations. CONCLUSIONS: Compared with earlier years, the reported number of ART cycles in Europe increased and the pregnancy rates increased marginally, even though fewer embryos were transferred and the multiple delivery rates were reduced.


Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS

Abstract: Oligomenorrhea and polycystic ovaries in women are one of the most important causes of the high incidence of ovulation failure. This is linked, perhaps, to insulin resistance and related metabolic features. A small number of reports show that myo-inositol improves ovarian function, but in these trials the quality of evidence supporting ovulation is suboptimal. Furthermore, few of them have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 92 patients randomized, 47 received 400 mcg folic acid as placebo, and 45 received myo-inositol plus folic acid (4 g myo-inositol plus 400 mcg folic acid). The ovulation frequency assessed by the ratio of luteal phase weeks to observa-tion weeks was significantly (P < 0.01) higher in the treated group (25%) compared with the placebo (15%), and the time to first ovulation was significantly (P < 0.05) shorter [24.5 d; 95% confidence interval (CI), 18, 31; compared with 40.5 d; 95% CI, 27, 54]. The number of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of myo-inositol on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the myo-inositol group. A significant increase in circulating high-density lipoprotein was observed only in the myo-inositol-treated group. Metabolic risk factor benefits of myo-inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). After 14-wk myo-inositol or placebo therapy, no change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded. There was an inverse relationship between body mass and treatment efficacy. In fact a significant weight loss (and leptin reduction) (P < 0.01) was recorded in the myo-inositol group, whereas the placebo group actually increased weight (P < 0.05). These data support a beneficial effect of myo-inositol in women with oligomenorrhea and polycystic ovaries in improving ovarian function.

European Review for Medical and Pharmacological Sciences


Cervical cancer and hormonal contraceptives: collaborative reanalysis of  individual data for 16,573 women with cervical cancer and 35,509 women without  cervical cancer from 24 epidemiological studies

International Collaboration of Epidemiological Studies of Cervical Cancer

Silvia Franceschi

Centre International de Recherche sur le Cancer

Abstract:
Background: Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use.

Methods: Individual data for 16,573 women with cervical cancer and 35,509 without cervical cancer were reanalysed centrally. Relative risks of cervical cancer were estimated by conditional logistic regression, stratifying by study, age, number of sexual partners, age at first intercourse, parity, smoking, and screening.

Findings: Among current users of oral contraceptives the risk of invasive cervical cancer increased with increasing duration of use (relative risk for 5 or more years' use versus never use, 1.90 [95% CI 1.69-2.13]). The risk declined after use ceased, and by 10 or more years had returned to that of never users. A similar pattern of risk was seen both for invasive and in-situ cancer, and in women who tested positive for high-risk human papillomavirus. Relative risk did not vary substantially between women with different characteristics.

Interpretation: The relative risk of cervical cancer is increased in current users of oral contraceptives and declines after use ceases. 10 years' use of oral contraceptives from around age 20 to 30 years is estimated to increase the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000 in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.


Diet and lifestyle in the prevention of ovulatory disorder infertility

Abstract:
OBJECTIVE: To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility.

METHODS: We followed a cohort of 17,544 women without a history of infertility for 8 years as they tried to become pregnant or became pregnant. A dietary score based on factors previously related to lower ovulatory disorder infertility (higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low glycemic carbohydrates, high fat dairy, multivitamins, and iron from plants and supplements) and other lifestyle information was prospectively related to the incidence of infertility.

RESULTS: Increasing adherence to a "fertility diet" pattern was associated with a lower risk of ovulatory disorder infertility. The multivariable-adjusted relative risk of ovulatory disorder infertility comparing women in the highest with women in the lowest quintile of the "fertility diet" pattern score was 0.34 (95% confidence interval 0.23-0.48; P for trend<.001). This inverse relation was similar in subgroups defined by women's age, parity, and body weight. A combination of five or more low-risk lifestyle factors, including diet, weight control, and physical activity was associated with a 69% lower risk of ovulatory disorder infertility and an estimated population attributable risk of 66% (95% confidence interval 29-86%).

CONCLUSION: Following a "fertility diet" pattern may favorably influence fertility in otherwise healthy women. Further, the majority of infertility cases due to ovulation disorders may be preventable through modifications of diet and lifestyle.

LEVEL OF EVIDENCE: II.


The association between body mass index and health-related quality of life: data from CaMos, a stratified population study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Background: Deviation from normal weight is associated with health risks, but less is known about the association between weight and health-related quality of life (HRQOL). We investigated this in the context of a population-based study, using a standard five-category weight classification system based on body mass index (BMI).

Methods: The Canadian Multicentre Osteoporosis Study is a randomly selected sample of men and women over 25 years of age from nine centres across Canada. Data were obtained by interview, and height and weight were measured and used to calculate BMI. HRQOL was measured using the SF-36. Multivariable linear regression was used to identify the association between BMI category and SF-36 scores after controlling for potential confounders.

Results: Complete data were available for 6,302 women and 2,792 men. Mean BMI for every age and gender group exceeded healthy weight guidelines. For women, being underweight, overweight or obese was associated with poorer HRQOL in most SF-36 outcomes while for men, this was associated with poorer HRQOL in some domains and with higher HRQOL in others.

Conclusions: A significant proportion of the population may be putting their health at risk due to excess weight, which may have a substantial negative effect on HRQOL, particularly in women. This underscores the need for continued public health efforts aimed at combating overweight and obesity.


The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)  statement: guidelines for reporting observational studies

Abstract: Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.


Abstract 3614: Anticonceptive Drug Use And Increased Carotid and Femoral Plaque Prevalence: Population Data From Asklepios

Marc De Buyzere

Ghent Univ, Gent, Belgium; On Behalf of the Asklepiosa Investigators

Peter Cassiman

Association of Primary Care Physicians Asklepios VOF, Nieuwerkerken-Aalst, Belgium

Abstract:
Purpose: Combination therapy with the female hormones estrogen (E) and progestins are very frequently used with approximately 100 million women worldwide taking oral contraceptives (OC). Recent trials have cast doubt on the cardiovascular safety of hormonal replacement therapy (HRT). In contrast to the HRT-controversy, little attention has been focused on OC, a therapy using 10 –100 fold higher levels of E than HRT. We describe population correlates of long-term OC use.

Methods: The Asklepios study is a representative sample (2524 M/F volunteers, 35–55 years) from the Belgian general population free from overt cardiovascular disease. Vascular echography of the carotid and femoral arteries was systematically performed and atherosclerosis was defined by presence of carotid or femoral plaque.

Results: Of 1301 women (median age 45.7 y), 27.4% were taking OC and 10.0% were taking HRT. In contrast, past OC-use is far more prevalent: 81% of women having taken OC for at least 1 year, with a median exposition of 13 years. After multivariate adjustment for age, smoking, blood pressure, lipids, obesity, diabetes, physical activity, fruit, vegetable and alcohol intake, educational level and drug therapy (lipid-lowering, antihypertensive, aspirin), use of OC was associated with a significant increase in carotid or femoral unilateral plaque. Odds ratio’s (OR) per 10 years of OC exposure were: carotid plaque 1.17 (1.00 –1.33) and femoral plaque 1.28 (1.10 –1.47). We also looked at prevalence of bilateral disease (involvement of right and left carotid/femoral artery) as a more stringent phenotype of atherosclerosis. OR per 10 years OC exposure were: carotid plaque 1.42 (1.03–1.84); femoral plaque 1.34 (1.05–1.63).

Interpretation : Use of contraceptive therapy is very common and associated with an unexpected increase in the prevalence of carotid and femoral atherosclerosis in otherwise young, apparently healthy women. Our data suggest a 20 –30% increased prevalence of plaque in the carotid and femoral arteries per 10 years of OC exposure. In the light of widespread (>80% of our population sample; > 100 million women globally) and usually prolonged OC use (>10 years) these results suggest OC use could be an important factor in the global atherosclerotic burden.


The osteoporosis care gap in men with fragility fractures: the Canadian  Multicentre Osteoporosis Study

Alexandra Papaioannou

McMaster University, Hamilton, ON, Canada

Abstract:
We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap.
Introduction: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos).

Methods: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five.

Results: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five).

Conclusions: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

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


Proximal tubal disease: the place for tubal cannulation

Soumen Das

Institute of Post Graduate Medical Education and Research

Abstract: Tubal disease is the cause of subfertility in approximately 30% of women, and 10-25% of these are due to proximal tubal obstruction. False-positive diagnosis of proximal tubal obstruction can be as high as 50%. A decrease in expertise in tubal microsurgery has resulted largely from the use of IVF as the treatment option for most causes of infertility and more specifically for tubal factor infertility. Selective salpingography and tubal cannulation have a unique role in the management of tubal infertility and should be offered to selected candidates prior to IVF. Tubal cannulation can be used effectively to restore patency in a proportion of cases of proximal tubal obstruction thus avoiding the need for expensive assisted reproductive techniques. This review examines the evidence supporting the effectiveness of tubal cannulation and aims to enhance awareness of the procedure as an option for the management of female subfertility secondary to isolated proximal tubal obstruction.


Contraceptive discontinuation attributed to method dissatisfaction in the United  States

James Trussell

Princeton University; Office of Population research; Wallaca Hall Princeton New Jersey USA NJ 08544

Abstract:
Background: This study examines contraceptive discontinuation due to method dissatisfaction among women in the United States.

Study Design: The study population, drawn from the 2002 National Survey of Family Growth, consisted of 6724 women (15-44 years of age) who had ever used a reversible contraceptive method. We first estimated the overall proportion of women who had ever discontinued their contraceptive due to dissatisfaction. We then calculated method-specific discontinuation risks due to dissatisfaction and analyzed the reasons for dissatisfaction given by women who had ever stopped using Norplant, Depo-Provera, oral contraceptives or condoms.

Results: Overall, 46% of women had ever discontinued at least one method because they were unsatisfied with it. Dissatisfaction-related discontinuation risks varied widely by method: the diaphragm and cervical cap showed the highest proportions of such discontinuation (52%), followed by long-acting hormonal methods (42%). Oral contraceptives were associated with an intermediate risk of dissatisfaction-related discontinuation (29%), while condoms had the lowest risk (12%).

Conclusion: A broader understanding of women's concerns and experiences using contraception could help health care providers redesign counseling strategies to improve contraceptive continuation.


Evidence of subpopulations with different levels of insulin resistance in women  with polycystic ovary syndrome

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract:
Background: Polycystic ovary syndrome (PCOS) is non-uniformly associated with insulin resistance (IR). We examined IR in women with PCOS.

Methods: Sixty-nine PCOS women were subjected to the insulin suppression test (IST) to determine their steady-state plasma glucose (SSPG) as a direct measure of insulin sensitivity.

Results: SSPG exhibited a multimodal distribution suggesting the existence of subpopulations. The heterogeneous distribution of plasma glucose at 180 min (P = 0.011), with three modes, suggested differences in the plasma glucose level trajectories during the IST. Hence, the population was separated into three groups: (i) (n = 33), subjects with SSPG < or = 152.5 mg/dl, corresponding to the first to fifth deciles; (ii) (n = 29), subjects in the interval 152.5 mg/dl < SSPG < or = 300 mg/dl; (iii) (n = 7), subjects with SSPG > 300 mg/dl, corresponding to the tenth decile. Plasma glucose distributions at 180 min showed differences in their mean values and ranges among groups (P < 0.0001). The trajectories of the groups differed significantly during the IST (P < 0.0001).

Conclusions: insulin sensitivity in our patients exhibited a discontinuous distribution, implying that PCOS is a heterogeneous disorder possessing subpopulations regarding IR.


Oral contraceptives and survival in breast cancer patients aged 20 to 54 years

Katrina F Trivers

Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Highway, NE, MS K-52, Atlanta, GA 30341, USA. ktrivers@cdc.gov

Jianwen Cai

University of North Carolina at Chapel Hill

Ralph J Coates

National Center for Chronic Disease Prevention and Health Promotion

Elaine W Flagg

Surveillance and Epidemiology Branch, Divisions of Global Migration and Quarantine and

Abstract: Recent oral contraceptive (OC) use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All-cause mortality was ascertained through the National Death Index (n = 292 deaths). Ageand income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29-4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years.

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


Thigh abscess mistaken for sarcoma following transobturator tape: a case report  and literature review

Abstract: A 44-year-old female, 1 year status-post ObTape transobturator mid-urethral sling, was evaluated by orthopaedic oncology and urology for persistent thigh pain and a left thigh mass. Multiple muscle biopsies were inconclusive, raising concern for inflammatory sarcoma. After serial débridements of the thigh abscess, sling material was found in the obturator space, which gave the diagnosis. Health care providers, both gynecologic and nongynecologic, need to be aware of serious complications of transobturator slings that may present in atypical ways.

Journal of Minimally Invasive Gynecology


Interstitial cystitis and systemic autoimmune diseases

Joop P van de Merwe

Erasmus MC, University Medical Center Rotterdam, Departments of Immunology and Internal Medicine, Dr Molewaterplein 50, Rotterdam, The Netherlands. email@jpvandemerwe.nl

Abstract: The cause of interstitial cystitis, a chronic disease that affects the bladder, is unknown. Autoantibodies, such as those against nuclear and bladder epithelium antigens, have been found in patients with interstitial cystitis, but these are likely to be secondary to the disease. No data support a direct causal role of autoimmune reactivity in the pathogenesis of interstitial cystitis. Indirect evidence, however, does support a possible autoimmune nature of interstitial cystitis, such as the strong female preponderance and the clinical association between interstitial cystitis and other known autoimmune diseases within patients and families. The strongest association occurs between interstitial cystitis and Sjögren's syndrome. Increasing evidence suggests a possible role of autoantibodies to the muscarinic M3 receptor in Sjögren's syndrome. The M3 receptor is also located on the detrusor muscle cells of the bladder and mediates cholinergic contraction of the urinary bladder and other smooth muscle tissues. Autoantibodies to the M3 receptor might be important in both the early noninflammatory and the late inflammatory features of interstitial cystitis.


Circadian rhythms, sleep, and the menstrual cycle

Abstract: Women with ovulatory menstrual cycles have a circadian rhythm superimposed on the menstrual-associated rhythm; in turn, menstrual events affect the circadian rhythm. In this paper, we review circadian rhythms in temperature, selected hormone profiles, and sleep-wake behavior in healthy women at different phases of the menstrual cycle. The effects on menstrual cycle rhythmicity of disrupted circadian rhythms, for example, with shiftwork and altered circadian rhythms in women with menstrual-related mood disturbances, are discussed. Compared to the follicular phase, in the post-ovulation luteal phase, body temperature is elevated, but the amplitude of the temperature rhythm is reduced. Evidence indicates that the amplitude of other rhythms, such as melatonin and cortisol, may also be blunted in the luteal phase. Subjective sleep quality is lowest around menses, but the timing and composition of sleep remains relatively stable across the menstrual cycle in healthy women, apart from an increase in spindle frequency activity and a minor decrease in rapid eye movement (REM) sleep during the luteal phase. Disruption of circadian rhythms is associated with disturbances in menstrual function. Female shiftworkers compared to non-shiftworkers are more likely to report menstrual irregularity and longer menstrual cycles. There also is accumulating evidence that circadian disruption increases the risk of breast cancer in women, possibly due to altered light exposure and reduced melatonin secretion. Further investigations into the biological consequences of circadian disruption in women will offer insight into some menstrual-associated disorders, including mood changes, as well as reproductive function and possible links with breast cancer.


Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1  acquisition among Kenyan women

Abstract:
Background: Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive.

Objective: To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population.

Methods: Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases.

Results: : Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00-2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28-2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64-7.82).

Conclusions: In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus.


Translation of an efficacious cancer-screening intervention to women enrolled in  a Medicaid managed care organization

Abstract:
Purpose: An earlier randomized controlled trial of prevention care management (PCM) found significant improvement in breast, cervical, and colorectal cancer-screening rates among women attending Community Health Centers but required substantial research support. This study evaluated the impact of a streamlined PCM delivered through a Medicaid managed care organization (MMCO), an infrastructure with the potential to sustain this program for the long term.

Methods: This randomized trial was conducted within an MMCO serving New York City between May 2005 and December 2005. A total of 1,316 women aged 40 to 69 years and not up to date for at least 1 targeted cancer-screening test were randomized to either PCM or a comparison group. Women in the PCM group received up to 3 scripted telephone calls to identify barriers and provide support to obtain any needed breast, cervical, and colorectal cancer-screening tests. Women in the comparison group received a modified version of the MMCO's established mammography telephone outreach program, also in up to 3 calls. Women in both groups received a financial incentive on confirmation that they had received a mammogram. Screening status was assessed through MMCO administrative data. Groups were compared using odds ratios.

Results: In an intent-to-treat comparison adjusted for baseline screening status, PCM women were 1.69 times more likely to be up-to-date for colorectal cancer-screening tests at follow-up than women in the comparison group (95% confidence interval, 1.03-2.77). Follow-up screening rates for cervical and breast cancer did not differ significantly between study groups on an intent-to-treat basis.

Conclusions: The abbreviated PCM telephone intervention was feasible to deliver through an MMCO and improved screening for 1 cancer. This approach has the potential to improve cancer-screening rates significantly in settings that can provide telephone support to women known to be overdue.


Contemporary risks of maternal morbidity and adverse outcomes with increasing maternal age and plurality

Abstract:
OBJECTIVE: To evaluate the risks of pregnancy complications and adverse outcomes associated with increasing maternal age and higher plurality.

DESIGN: Population-based, historic cohort study.

SETTING: US birth certificates and infant death certificates.

PATIENT(S): Live births of > or =20 weeks gestation between 1995-2000: 22,991,306 singleton, 316,696 twin, and 12,193 triplet pregnancies.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Pregnancy-associated hypertension, incompetent cervix, tocolysis, premature rupture of membranes, excessive bleeding at delivery, delivery <29 weeks, and infant death.

RESULT(S): Compared to singletons, the risks for all adverse outcomes among multiple pregnancies were significantly elevated, and were highest for tocolysis, delivery <29 weeks, and infant mortality. Within pluralities, increasing maternal age was associated with significantly higher risks of pregnancy-associated hypertension, excessive bleeding, and incompetent cervix, but for twin and triplet pregnancies, significantly lower risks for tocolysis (ages > or =40, singleton adjusted odds ratio [AOR] 0.97, twin AOR 0.67, triplet AOR 0.72), delivery <29 weeks (ages > or =40, singleton AOR 1.55, twin AOR 0.72, triplet AOR 0.52), and infant mortality (ages > or =40, singleton AOR 1.34, twin AOR 0.71, triplet AOR 0.42).

CONCLUSION(S): Older maternal age and higher plurality are each associated with increasing risks for many pregnancy complications, but with significantly lower risks of tocolysis, early preterm birth, and infant mortality.


Fragility fractures and bone mineral density in HIV positive women: a case-control population-based study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
This Canadian study of bone health showed that HIV+ women were more likely to have had fragility fractures (OR 1.7) but had BMD values that were not different than women from a national population-based cohort.
Introduction: Given that 17.5 million women globally are HIV-infected and living longer on anti-retroviral therapy (ART+), it is essential to determine whether they are at risk for osteoporosis as is currently assumed.

Methods: Assessment of osteoporosis risk factors and lifetime low-trauma (fragility) fracture history used a common interviewer-administered questionnaire and phantom-adjusted bone mineral density (BMD). This study compared HIV+ Canadian women with ageand region-matched control women (1:3) from a national population-based study of osteoporosis.

Results: One hundred and thirty-eight HIV+ women (100 ART+, 38 ART-) were compared with 402 controls. There were no differences in age (37.7 vs. 38.0 years), BMI (25.0 vs. 26.2), family history of osteoporosis, exercise history, alcohol or calcium intakes, age at menarche, oral contraceptive use or parity. HIV+ cases included more Aboriginal and Black women (12.5% and 16.2 vs. 2% and 1%, respectively), smoked and used injection drugs (53%) more, were more often treated with glucocorticoids, had oligomenorrhea, and reported 10-kg weight cycling. Significantly more HIV+ women reported lifetime fragility fractures (26.1% vs. 17.3; OR 1.7, 95% CI 1.1, 2.6). HIV+ and control women did not differ in BMD: spine 1.0 +/- 0.12 vs.1.0 +/- 0.14 g/cm(2) (diff. 0.0, 95% CI -0.27, 0.27) or total femur 0.91 +/- 0.15 vs. 0.93 +/- 0.12 g/cm(2) (diff 0.02, 95% CI +0.005, -0.045).

Conclusion: HIV+ women reported significantly more past osteoporotic fractures than population-based controls despite normal BMD. Research is needed to assess bone microarchitecture and develop a reliable fracture risk assessment tool for HIV+ women.


Oral, injected and implanted contraceptives and breast cancer risk among U.S.  Hispanic and non-Hispanic white women

Abstract: Associations between oral contraceptive (OC) use and breast cancer have been reported, but few studies have considered associations in racial and ethnic minorities. Data regarding injected or implanted hormonal contraceptives are limited. In a case-control study of Hispanic (796 cases, 919 controls) and non-Hispanic white (1,522 cases, 1,596 controls) women in the U.S. southwest interviewed in 2000-2005, 49% of Hispanic controls and 66% of non-Hispanic white controls reported having used OC. Breast cancer odds ratios (OR) associated with OC use within the past 5 years were 1.22 (95% confidence interval (CI) 0.80, 1.84) among Hispanics, 1.28 (95% CI 0.93, 1.76) among non-Hispanic whites, 1.27 (95% CI 0.99, 1.63) for both ethnic groups combined and 1.53 (95% CI 0.98, 2.40) for estrogen receptor (ER) negative tumors. OC use for 20 years or longer was associated with ORs of 1.50 (95% CI 1.04, 2.17) for both ethnic groups combined, and 2.23 (95% CI 1.17, 4.25) for ER negative tumors. Hormonal contraceptive injections were used by 3.3% of Hispanic controls and 2.8% of non-Hispanic white controls, OR 1.23 (95% CI 0.88, 1.73). Fifteen cases and 2 controls reported use of a subdermal contraceptive implant, OR 8.59 (95% CI 1.92, 38.39). Associations between OC use and breast cancer in Hispanics are consistent with modestly increased risk among recent users and for ER negative tumors, as observed in other populations. Based on a small number of users of contraceptive implants, a significantly increased breast cancer risk was observed; continued surveillance of implant users may be warranted.


Influences of hormone-based contraception on depressive symptoms in premenopausal  women with major depression

Madhukar H Trivedi

The University of Texas Southwestern Medical Center

Abstract:
Objective: Hormone-based contraceptives affect mood in healthy women or in women with premenstrual dysphoric disorder (PMDD). No study has yet examined their association with mood in women with major depressive disorder (MDD). The purpose of this study was to determine whether estrogen-progestin combination or progestin-only contraceptives are associated with depression severity, function and quality of life, or general medical or psychiatric comorbidity in women with MDD.

Methods: This analysis focused on a large population of female outpatients less than 40 years of age with non-psychotic MDD who were treated in 18 primary and 23 psychiatric care settings across the US, using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Baseline demographic and clinical information was gathered and compared between three groups based on hormonal use: combination (estrogen-progestin)(N=232), progestin-only (N=58), and no hormone treatment (N=948).

Results: Caucasians were significantly more likely to use combined hormone contraception. Women on progestin-only had significantly more general medical comorbidities; greater hypersomnia, weight gain and gastrointestinal symptoms; and worse physical functioning than women in either of the other groups. Those on combined hormone contraception were significantly less depressed than those with no hormone treatment by the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated. The combined hormone group also demonstrated better physical functioning and less obsessive-compulsive disorder (COCD) comorbidity than either of the other groups.

Conclusions: Synthetic estrogen and progestins may influence depressive and physical symptoms in depressed women.


Changes in body mass index in Canadians over a five-year period: results of a prospective, population-based study

Abstract:
Background: The initiation of the Canadian Multicentre Osteoporosis Study in 1996, and subsequent follow-up of the cohort 5 years later, provided longitudinal body mass index (BMI) data for a random sample of Canadians.

Methods: Height and weight were measured at baseline and 5 years and used to calculate BMI and assign one of six weight categories. Multiple imputation was used to adjust for missing weight at year 5. Data were stratified by age and gender. The proportion of participants moving between categories was generated, and multivariable linear regression was used to identify factors associated with weight change.

Results: Baseline data were available for 8548 participants, year 5 data for 6721, and year 5 weight was imputed for 1827 (17.6%). Mean BMI for every age and gender group exceeded healthy weight guidelines. Most remained within their BMI classification over 5 years, but when change occurred, BMI category was more likely to increase than decrease. Several sociodemographic, lifestyle and clinical characteristics were associated with change.

Conclusion: Mean baseline BMI tended to be higher than recommended. Moreover, on average, men under age 45 and women under age 55 were gaining approximately 0.45 kilograms (one pound) per year, which leveled off with increased age and reversed in the oldest age groups. These findings underscore the need for public health efforts aimed at combating obesity.


Patterns of menstrual disturbance in eating disorders

Poyastro Pinheiro A, Thornton LM, Plotonicov KH, Tozzi F, Klump KL, Berrettini WH, Brandt H, Crawford S, Crow S, Fichter MM, Goldman D, Halmi KA, Johnson C, Kaplan AS, Keel P, LaVia M, Mitchell J, Rotondo A, Strober M, Treasure J, Woodside DB, Von Holle A, Hamer R, Kaye WH, Bulik CM

Abstract:
OBJECTIVE: To describe menstrual disturbance in eating disorders (ED).

METHOD: We describe menstrual history in 1,705 women and compare eating, weight, and psychopathological traits across menstrual groups.

RESULTS: Menstrual dysfunction occurred across all eating disorder subtypes. Individuals with normal menstrual history and primary amenorrhea reported the highest and lowest lifetime body mass index (BMI), respectively. Normal menstruation and oligomenorrhea groups reported greater binge eating, vomiting, and appetite suppressant use. Amenorrhea was associated with lower caloric intake and higher exercise. Harm avoidance, novelty seeking, perfectionism, and obsessionality discriminated among menstrual status groups. No differences in comorbid Axis I and II disorders were observed.

CONCLUSION: Menstrual dysfunction is not limited to any eating disorder subtype. BMI, caloric intake, and exercise were strongly associated with menstrual function. Menstrual status is not associated with comorbidity. Menstrual irregularity is an associated feature of all ED rather than being restricted to AN only.

The International journal of eating disorders


Treatment of menorrhagia

Treatment of menorrhagia

Abstract: Menorrhagia is defined as excessive uterine bleeding occurring at regular intervals or prolonged uterine bleeding lasting more than seven days. The classic definition of menorrhagia (i.e., greater than 80 mL of blood loss per cycle) is rarely used clinically. Women describe the loss or reduction of daily activities as more important than the actual volume of bleeding. Routine testing of all women with menorrhagia for inherited coagulation disorders is unnecessary. Saline infusion sonohysteroscopy detects intracavitary abnormalities such as endometrial polyps or uterine leiomyoma and is less expensive and invasive than hysteroscopy. Endometrial biopsy is effective for diagnosing precancerous lesions and adenocarcinoma but not for intracavitary lesions. Except for continuous progestin, medical therapies are limited. The levonorgestrel-releasing intrauterine device is an effective therapy for women who want to preserve fertility and avoid surgery. Surgical therapies include endometrial ablation methods that preserve the uterus; and hysterectomy, which results in high satisfaction rates but with potential surgical morbidity. Overall, hysterectomy and endometrial ablation result in the greatest satisfaction rates if future childbearing is not desired. Treatment of menorrhagia results in substantial improvement in quality of life.


Management of endometriosis in general practice: the pathway to diagnosis

Abstract:
BACKGROUND: The prevalence of endometriosis is estimated to be around 10%. Diagnosis is through visualisation of the lesions, mostly via laparoscopy. Studies reveal that there is an average delay in the diagnosis of endometriosis of between 8 and 12 years. Little is known about the reasons for delays in diagnosis women's experiences of primary care prior to diagnosis.

AIM: To investigate women's experiences of endometriosis from first presentation to diagnosis.

DESIGN OF STUDY: Retrospective analysis of data collected from primary care records in four general practices.

SETTING: General practice in south-east England.

METHOD: Women with a Read Code diagnosis of endometriosis were recruited to the study. Details of consultations, investigations, and referrals related to endometriosis were recorded from the notes. Data were analysed using descriptive statistics.

RESULTS: The prevalence of endometriosis in women aged over 16 years was 1.44%. A third of women had consulted their GP six or more times before being diagnosed. Ultrasound was frequently requested by GPs, but was helpful in diagnosing endometriosis in only 10.6% of women who underwent a scan. Thirty-nine per cent of women were referred to gynaecologists two or more times before a positive diagnosis was made. The median time from first presentation with symptoms to diagnosis was 9.0 years (interquartile range = 4.5-13.5 years).

CONCLUSION: Repeated consultations and negative investigations contribute to a median delay of 9.0 years before diagnosis of endometriosis. Further research into GPs' interpretation of symptoms and patients' experiences of negative investigations and consultations may lead to a more positive outcome for women with this condition.

The British journal of general practice : the journal of the Royal College of General Practitioners


A pilot study of the feasibility of long-term human bone balance during perimenopause using a 41Ca tracer

Brian C Lentle

Department of RadiologyUniversity of British ColumbiaVancouverBCCanada

Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms


Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study

Abstract:
OBJECTIVE: To evaluate the effect of vaginal lubricants Pre-Seed, FemGlide, Astroglide, and Replens on human sperm motility and chromatin integrity.

DESIGN: Prospective, comparative, in vitro study.

SETTING: Andrology laboratory at tertiary care hospital.

PATIENT(S): Thirteen normozoospermic donors.

INTERVENTION(S): Semen samples from 13 subjects were incubated in human tubal fluid media (HTF) controls and 10% (vol/vol) of Pre-Seed, FemGlide, Astroglide, and Replens lubricants. After 30 minutes, progressive sperm motility was assessed by light microscopy. Semen samples of 12 patients were placed in positive control (HTF), negative control (10% K-Y Jelly lubricant), and 10% vol/vol Pre-Seed and FemGlide lubricants. After 4 hours culture, spermatozoa were analyzed for percent DNA fragmentation index with use of the acridine orange-based sperm chromatin structure assay.

MAIN OUTCOME MEASURE(S): Sperm motility and percent DNA fragmentation index.

RESULTS: Percent motility did not differ significantly between HTF controls and Pre-Seed, whereas FemGlide, Replens, and Astroglide lubricants demonstrated a significant decrease in motility. There was no significant difference in percent DNA fragmentation index between the HTF controls and Pre-Seed, but a significant decline in sperm chromatin quality occurred with FemGlide and K-Y Jelly.

CONCLUSION: Pre-Seed does not cause a significant decrease in progressive sperm motility or chromatin integrity in contrast to other lubricants used by couples.


Risk factors for early age at breast cancer onset--the "COSA program"  population-based study

Abstract:
Background: Breast cancer is the most frequent cancer in women in western countries. A number of risk factors are now known, but the etiology of the disease is not fully understood. The aim of this study was to determine the effects of reproductive, anthropometric and environmental factors on cancer onset. PATIENTS AND

Methods: 934 women who developed a non-hereditary breast cancer were recruited from different hospitals in the Auvergne region (France) and completed a questionnaire.

Results: The use of oral contraceptives (OC) increased the risk of early cancer development (odds ratio = 1.84, 95% confidence interval = 1.38-2.44). The age at first OC use appeared to be a major factor since the risk decreased when OC use was after the age of 23 years (odds ratio = 0.52, 95% confidence interval = 0.34-0.79). A duration of breast-feeding greater than 26 weeks decreased the risk of early cancer development (odds ratio = 0.62, 95% confidence interval = 0.39-0.97). No overall association was found with anthropometric or lifestyle factors and early age at breast cancer onset.

Conclusion: OC use, age at first OC use and lactation were significantly associated with an early age at breast cancer onset. Thus, a number of "risk factors" could be considered as "early onset risk factors".


Endometriosis is associated with a decreased risk of pre-eclampsia

Abstract:
Background: We postulated that impaired endometrial differentiation in women with pelvic endometriosis predisposes for pre-eclampsia.

Methods: A retrospective case-control study set at the University of Ghent IVF centre. The incidence of pre-eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or laparoscopic diagnosis of endometriosis-associated infertility (case group; n = 245 pregnancies) was compared with the incidence of these obstetric complications in pregnancies following treatment for male-factor infertility (control group; n = 274 pregnancies). Pregnancy data were obtained by searching electronic databases and postal questionnaires. The case and control groups were matched for age, parity and multiple pregnancies.

Results: The incidence of pre-eclampsia was significantly lower in the case group (0.8%) when compared with control group (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7-33.3). Analysis of obstetric outcome in the subgroup of patients with laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%) versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2-37). PIH occurred in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR = 2.6, 95% CI: 1.2-6.0). The odds of developing pre-eclampsia were 5.67 times higher in the control group than in pregnancies following endometriosis-associated infertility. In multiple pregnancies, the odds of developing pre-eclampsia increased 1.93 times per additional child, with or without endometriosis.

Conclusions: We found no evidence that endometriosis predisposes for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is significantly reduced in women with endometriosis-associated infertility.


The length of the fertile window is associated with the chance of spontaneously  conceiving an ongoing pregnancy in subfertile couples

M J Keulers

Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. m.keulers@haio.umcn.nl

C J C M Hamilton

Abstract: The period in each menstrual cycle during which sexual intercourse can result in conception is called the "fertile window". Although the fertile window closes on the day of ovulation, little is known about the moment it opens. We defined the first day of normal sperm-mucus interaction as the opening of the fertile window. We hypothesized that length of the fertile window varies between couples and that the number of days the fertile window is "open" is related to the time to spontaneous conception. METHODS Serial post-coital tests and sperm-mucus penetration tests were performed to detect the first normal sperm-mucus interaction day. Ovulation was confirmed by serial ultrasound. Using Cox' regression analysis, we determined whether the fertile window length was associated with time to ongoing pregnancy. This association was expressed in fecundability ratios (FR). RESULTS The fertile window length was determined in 410 subfertile couples. The fertile window length varied among couples from <1 to >5 days. The FR increased with increasing fertile window length and varied between 0.11 (95% CI: 0.03-0.45) for a fertile window of 1 day, to 2.4 (95% CI: 1.1-5.2) for a fertile window of 5 days or more. CONCLUSIONS The longer the fertile window in subfertile couples, the higher is the probability of spontaneously conceiving an ongoing pregnancy.


The safety of a drospirenone-containing oral contraceptive: final results from  the European Active Surveillance Study on oral contraceptives based on 142,475  women-years of observation

Jürgen C. Dinger

Center for Epidemiology and Health Research (ZEG), 10115 Berlin, Germany. dinger@zeg-berlin.de

Abstract:
Objectives: The study was conducted to compare risks of adverse cardiovascular and other events associated with the use of drospirenone (DRSP)-containing oral contraceptives (OCs) and other OCs. METHODS AND MATERIALS: The European Active Surveillance study (EURAS) was a multinational, prospective, noninterventional cohort study of new users of DRSP, levonorgestrel (LNG) and other progestin-containing OCs. Semiannual follow-up was based on mailed questionnaires, with additional follow-up procedures when needed.

Results: Overall, 58,674 women were followed for 142,475 women-years of observation. Loss to follow-up was 2.4%. Serious adverse and fatal events were rare, and rate ratios were close to unity (1.0). Cox regression analysis of cardiovascular outcomes yielded hazard ratios for DRSP-containing vs. LNG-containing and other OCs of 1.0 and 0.8 (upper 95% confidence limits, 1.8 and 1.3) for venous, and 0.3 and 0.3 (upper 95% confidence limits, 1.2 and 1.5) for arterial thromboembolism, respectively.

Conclusions: Risks of adverse cardiovascular and other serious events in users of a DRSP-containing OC are similar to those associated with the use of other OCs.


Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a  1-year randomized double-blind trial following premenopausal ovariectomy

Ewoud ter Avest

Division of General Internal Medicine, Department of Medicine, Radboud University, Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands

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: Oestrogen therapy is the gold standard treatment for hot flushes/night sweats, but it and oestrogen/progestin are not suitable for all women. MPA (medroxyprogesterone acetate) reduces hot flushes, but its effectiveness compared with oestrogen is unknown. In the present study, oral oestrogen [CEE (conjugated equine oestrogen)] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year randomized double-blind parallel group controlled trial in an urban academic medical centre. Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease. A total of 41 women {age, 45 (5) years [value is mean (S.D.)]} were enrolled; 38 women were included in this analysis of daily identical capsules containing CEE (0.6 mg/day) or MPA (10 mg/day). Demographic variables did not differ at baseline. Daily data provided the number of night and day flushes compared by group. The vasomotor symptom day-to-day intensity change was assessed by therapy assignment. Hot flushes/night sweats were well controlled in both groups, one occurred on average every third day and every fourth night. Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively, but were not significantly different (P=0.156). Night sweats also did not differ significantly (P=0.766). Therapies were statistically equivalent (within one event/24 h) in the control of vasomotor symptoms. Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE (P<0.001). In conclusion, this analysis demonstrates that MPA and CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy.

Clinical Science (London, England : 1979)


Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort

Immo Kleinschmidt

London School of Hygiene & Tropical Medicine

Abstract:
Objective: To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception.

Methods: Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year.

Results: There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study.

Conclusions: There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.


Psychological impact of infertility

Psychological impact of infertility

Abstract: The inability to conceive children is experienced as a stressful situation by individuals and couples all around the world. The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood. Evidence is emerging of an association between stress of fertility treatment and patient drop-out and pregnancy rates. Fortunately, psychological interventions, especially those emphasizing stress management and coping-skills training, have been shown to have beneficial effects for infertility patients. Further research is needed to understand the association between distress and fertility outcome, as well as effective psychosocial interventions.

Best practice & research. Clinical obstetrics & gynaecology


Reproductive and menopausal factors and risk of systemic lupus erythematosus in  women

Abstract:
Objective: Systemic lupus erythematosus (SLE) occurs predominantly in women, and hormones may play a role in its etiology. This study was carried out to examine associations between female reproductive and menopausal factors and the development of SLE.

Methods: A cohort of 238,308 women was prospectively examined. Subjects were older women (ages 30-55 years at start) and younger women (ages 25-42 years at start) from the Nurses' Health Study (NHS) and NHSII cohorts. Incident SLE diagnosed between 1976 and 2003 was confirmed by medical record review. The relative risk (RR) of SLE was estimated separately in each cohort using Cox proportional hazards models, and then pooled using meta-analysis random effects models.

Results: Two hundred sixty-two incident cases of SLE were confirmed among the women. In multivariable models adjusted for reproductive and other risk factors, age<or=10 years at menarche (pooled RR 2.1, 95% confidence interval [95% CI] 1.4-3.2), oral contraceptive use (pooled RR 1.5, 95% CI 1.1-2.1), and use of postmenopausal hormones (RR 1.9, 95% CI 1.2-3.1) significantly increased the risk of SLE. An elevation of SLE risk was observed among postmenopausal women primarily after surgical menopause (RR 2.3, 95% CI 1.2-4.5), and also among women with earlier age at natural menopause (P for trend<0.05). Menstrual irregularity was associated with an increased risk of SLE among women in the younger (NHSII) cohort. Age at first birth, parity, and total duration of breastfeeding were not associated with SLE.

Conclusion: Early age at menarche, oral contraceptive use, early age at menopause, surgical menopause, and postmenopausal use of hormones were each associated with an increased risk of SLE. These associations may point to the mechanisms underlying the pathogenesis of SLE.


Risk factors for breast cancer in Turkish women: a hospital-based case-control  study

Abstract: The aim of this study was to investigate the association between risk factors and breast cancer in Turkish women. In a hospital-based case-control study in Istanbul, 405 patients with histologically confirmed breast cancer were compared with 1050 controls, who were admitted to different departments of the same hospital. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor were obtained from logistic regression analyses. Risk factors for breast cancer were found to be early menarche age (OR 3.87, 95% CI 2.46-6.08), use of alcohol (OR 3.87, 95% CI 1.79-8.37), history of diabetes (OR 3.31, 95% CI 2.36-4.64) or hypertension (OR 3.44, 95% CI 2.07-5.71), oral contraceptive use (OR 1.98, 95% CI 1.38-2.85) and hormone replacement therapy (HRT) use (OR 1.94, 95% CI 1.15-3.29). The findings of the present study indicated that history of diabetes or hypertension, use of alcohol, oral contraceptive and HRT, never having breastfed and delayed age at first birth associated with changing of lifestyle led to an increased risk of breast cancer in Turkish women.


Efficacy of cervical mucus observations plus electronic hormonal fertility  monitoring as a method of natural family planning

Abstract:
Objective: To determine the effectiveness of an electronic hormonal fertility monitor plus cervical mucus monitoring to avoid pregnancy.
Design: A 12-month prospective clinical efficacy trial. SETTING AND

Participants: One hundred ninety five (195) women (mean age 29.8 years) seeking to avoid pregnancy with a natural method at 5 clinical sites in 4 cities.

Intervention: Each participant was taught to track fertility by self-observation of cervical mucus and an electronic monitor that measures urinary levels of estrone-3-glucuronide and luteinizing hormone.

Main Outcome Measures: Correctand typical-use unintended pregnancy rates.

Results: There were a total of 26 unintended pregnancies, 3 with correct use. With 1,795 months of use, the correct-use pregnancy rate was 2.1% per 12 months of use (i.e., 97.9% effective in avoiding pregnancy when rules of the method were always followed) and the imperfect-use pregnancy rate was 14.2% per 12 months of use (i.e., 85.8% effective in avoiding pregnancy when rules of the method were not always followed and all unintended pregnancies and months of use were included in the calculations).

Conclusions: Correct use of an electronic hormonal fertility monitor with cervical mucus observations can be as effective as other fertility awareness-based methods of natural family planning. Comparative studies are needed to confirm this conclusion.

Journal of Obstetric, Gynecologic, and Neonatal Nursing : JOGNN


Hormone replacement therapy and breast cancer in former users of oral  contraceptives--The Norwegian Women and Cancer study

Abstract: Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.


N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic  ovary syndrome: a cross-over trial

Abstract:
Objective: To compare clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome.
Design: Prospective cross-over trial.
Setting: University teaching hospital and a private practice setting.

Patients: Five hundred and seventy-three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N-acetyl cysteine for another cycle. All women suffered from polycystic ovary syndrome.

Interventions: Patients had clomiphene citrate 50-mg tablets twice daily alone or with N-acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle.

OUTCOME MEASURES: Primary outcomes were number of mature follicles, serum E2, serum progesterone, and endometrial thickness. Secondary outcome was the occurrence of pregnancy.

Results: Ovulation rate improved significantly after the addition of N-acetyl cysteine (17.9% versus 52.1%). Although the number of mature follicles was more in the N-acetyl cysteine group (2.1+/-0.88 versus 3.2+/-0.93), the difference was not statistically significant. The mean E2 levels (pg/ml) at the time of human chorionic gonadotropine injection, serum progesterone levels (ng/ml) on days 21-23 of the cycle, and the endometrial thickness were significantly improved in the N-acetyl cysteine group. The overall pregnancy rate was 11.5% in the N-acetyl cysteine group. Insulin resistance occurred in 260 patients (55.4%). There was no significant difference between the insulin resistance group (n = 260) and non-insulin resistance group (n = 210) as regards ovulation rate, number of follicles, serum E2 (pg/ml), serum progesterone (ng/ml), endometrial thickness (mm), or pregnancy rate.

Conclusion: N-Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients.

Acta Obstetricia Et Gynecologica Scandinavica


Effectiveness of ERr 731 in the management of symptomatic perimenopause: clinical significance

Abstract: Prior, Jerilynn C. MD, FRCPC1; Klauss, Vanadin Seifert MD2; Kalyan, Shirin PhD1; Pride, Sheila MD, FRSCPC3


Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding?

Malcolm G Munro

Kaiser Permanente West Los Angeles Medical Center

Abstract: BACKGROUND: There is considerable worldwide confusion in the use of terminologies and definitions around the symptom of abnormal uterine bleeding (AUB), and these are leading increasingly to difficulties in setting up multinational clinical trials and in interpreting the results of studies undertaken in single centres. An international initiative was established to develop an agreement process to recommend clear, simple terminologies and definitions with the potential for wide acceptance. METHODS: After widespread consultation with relevant international and national organizations, journal editors and individuals, a modified Delphi process was developed to assess the current use of terminologies followed by a structured face-to-face meeting of 35 clinicians (mostly gynaecologists) and scientists in Washington. Focused small group discussions led to plenary assessment of concepts and recommendations using an electronic keypad voting system. RESULTS: There was almost universal agreement that poorly defined terms of classical origin used in differing ways in the English medical language should be discarded and that these should be replaced by simple, descriptive terms with clear definitions which have the potential to be understood by health professional and patient alike and which can be translated into most languages. The major recommendations were to replace terms such as menorrhagia, metrorrhagia, hypermenorrhoea and dysfunctional uterine bleeding. Suggestions for potentially suitable replacement terms and definitions are made. CONCLUSIONS: A simple terminology has been recommended for the description and definition of symptoms and signs of AUB. This manuscript should be a living document and should be part of an ongoing process with international medical and community debate. Classification of causes, investigations and cultural and quality of life issues should be part of the ongoing process.


Levonorgestrel emergency contraception: a joint analysis of effectiveness and mechanism of action

Abstract:
OBJECTIVE: To model the effectiveness that can be obtained if levonorgestrel-only emergency contraception (EC) acts only through disrupting ovulation, in relation to other effects that may occur before or after fertilization and accounting for delays in administration.

DESIGN: We modeled follicular growth as a function of follicular size, using known day-specific probabilities of conception and known disruption of ovulation by levonorgestrel-only EC, to estimate the expected effectiveness of EC.

SETTING: Combined data from multiple clinical studies.

PATIENT(S): Simulation models.

INTERVENTION(S): Disruption of ovulation.

MAIN OUTCOME MEASURE(S): Effectiveness in the form of proportion of pregnancies prevented.

RESULT(S): With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay).

CONCLUSION(S): The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects. Additional data with follicular ultrasound and precise measures of delay between intercourse and EC administration would yield greater insight into effectiveness and mechanisms of action.


The effectiveness of a fertility awareness based method to avoid pregnancy in relation to a couple's sexual behaviour during the fertile time: a prospective longitudinal study

Petra Frank-Herrmann

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

Abstract:
BACKGROUND: The efficacy of fertility awareness based (FAB) methods of family planning is critically reviewed. The objective was to investigate the efficacy and the acceptability of the symptothermal method (STM), an FAB method that uses two indicators of fertility, temperature and cervical secretions observation. This paper will recommend a more suitable approach to measure the efficacy.

METHODS: Since 1985, an ongoing prospective observational longitudinal cohort study has been conducted in Germany. Women are asked to submit their menstrual cycle charts that record daily basal body temperature, cervical secretion observations and sexual behaviour. A cohort of 900 women contributed 17,638 cycles that met the inclusion criteria for the effectiveness study. The overall rates of unintended pregnancies and dropout rates have been estimated with survival curves according to the Kaplan-Meier method. In order to estimate the true method effectiveness, the pregnancy rates have been calculated in relation to sexual behaviour using the 'perfect/imperfect-use' model of Trussell and Grummer-Strawn.

RESULTS: After 13 cycles, 1.8 per 100 women of the cohort experienced an unintended pregnancy; 9.2 per 100 women dropped out because of dissatisfaction with the method; the pregnancy rate was 0.6 per 100 women and per 13 cycles when there was no unprotected intercourse in the fertile time.

CONCLUSIONS: The STM is a highly effective family planning method, provided the appropriate guidelines are consistently adhered to.


Silver-Russell syndrome in a girl born after in vitro fertilization: partial hypermethylation at the differentially methylated region of PEG1/MEST

Abstract: Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART.

Journal of Assisted Reproduction and Genetics


Effects of sexual intercourse patterns in time to pregnancy studies

David B Dunson

National Institute of Environmental Health Sciences

Abstract: Time to pregnancy, typically defined as the number of menstrual cycles required to achieve a clinical pregnancy, is widely used as a measure of couple fecundity in epidemiologic studies. Time to pregnancy studies seldom utilize detailed data on the timing and frequency of sexual intercourse and the timing of ovulation. However, the simulated models in this paper illustrate that intercourse behavior can have a large impact on time to pregnancy and, likewise, on fecundability ratios, especially under conditions of low intercourse frequency or low fecundity. Because intercourse patterns in the menstrual cycles may vary substantially among groups, it is important to consider the effects of sexual behavior. Where relevant and feasible, an assessment should be made of the timing and frequency of intercourse relative to ovulation. Day-specific probabilities of pregnancy can be used to account for the effects of intercourse patterns. Depending on the research hypothesis, intercourse patterns may be considered as a potential confounder, mediator, or outcome.


Changes to osteoporosis prevalence according to method of risk assessment

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Kerry Siminoski

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

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk.
Introduction: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD.

Materials and Methods: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds.

Results: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk.

Conclusions: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.


Effectiveness of levonorgestrel emergency contraception given before or after ovulation--a pilot study

Abstract:
BACKGROUND: Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation.

METHOD: Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined.

RESULTS: Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data.

CONCLUSION: These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.


Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study

Abstract:
OBJECTIVE: To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms.

METHODS: A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography.

RESULTS: The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group.

CONCLUSION: Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology


NICE says hysterectomy must be last option for heavy menstrual bleeding


Effect of selective serotonin reuptake inhibitors on the risk of fracture

Canadian Multicentre Osteoporosis Study Research Group

Abstract:
Background: Depression and osteoporotic fractures are common ailments among elderly persons. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of depression in this population, and the association between daily SSRI use and fragility fractures is unclear. Our objective was to examine the effect of daily SSRI use on the risk of incident clinical fragility fracture.

Methods: A population-based, randomly selected, prospective cohort study of 5008 community-dwelling adults 50 years and older, followed up over 5 years for incident fractures. Clinical fragility fractures were classified as minimal trauma fractures that were clinically reported and radiographically confirmed. The risk of fragility fracture associated with daily SSRI use was determined while controlling for relevant covariates.

Results: Daily SSRI use was reported by 137 subjects. After adjustment for many potential covariates, daily SSRI use was associated with substantially increased risk of incident clinical fragility fracture (hazard rate, 2.1; 95% confidence interval, 1.3-3.4). Daily SSRI use was also associated with increased odds of falling (odds ratio, 2.2; 95% confidence interval, 1.4-3.5), lower bone mineral density at the hip, and a trend toward lower bone mineral density at the spine. These effects were dose dependent and were similar for those who reported taking SSRIs at baseline and at 5 years' follow-up.

Conclusions: Daily SSRI use in adults 50 years and older remained associated with a 2-fold increased risk of clinical fragility fracture after adjustment for potential covariates. Depression and fragility fractures are common in this age group, and the elevated risk attributed to daily SSRI use may have important public health consequences.