Background: In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection. Methods: A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses. Results: During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97). Conclusions: Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.

Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.

Cytokines play a major role in bone remodeling in vitro and in animal models, with evidence supporting the involvement of inflammatory markers in the pathogenesis of osteoporosis. However, less is known about the longitudinal association of inflammatory markers with hip fracture. We tested whether high receptor levels of pro-inflammatory cytokines are associated with an increased risk of hip fracture in older women. We used a nested case-control study design from the Women's Health Initiative Observational Study (WHI-OS) and selected 400 cases with physician adjudicated incident hip fractures and 400 age, race, and date of blood draw matched controls. Participants were chosen from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Incident hip fractures (median follow-up 7.1 years) were verified by review of radiographs and confirmed by blinded central adjudicators. Hip fractures with a pathological cause were excluded. In multivariable models, the risk of hip fracture for subjects with the highest levels of inflammatory markers (quartile 4) compared with those with lower levels (quartiles 1, 2, and 3) was 1.43 (95% CI, 0.98 to 2.07) for IL-6 SR and 1.41 (95% CI, 0.97 to 2.05) for TNF SR1 and 1.57 (95% CI, 1.09 to 2.25) for TNF SR2. In subjects with all three markers in the highest quartile, the risk ratio of fracture was 2.27 (95% CI to 1.04 to 4.93) in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.042). Elevated levels of inflammatory markers for all 3 cytokine soluble receptors were associated with an increased risk of hip fractures in older women. Future clinical trials should test whether interventions to decrease inflammatory marker levels reduces hip fractures.

Objective-Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).* Corresponding author and address reprint requests to: Emily D. Szmuilowicz, MD, MS Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University 211 E. Chicago Ave., #1050 Chicago, IL 60611 edszmuilowicz@post.harvard.edu Phone: (312) 944-6677 x318, fax: (312) 944-3346. Financial disclosure/conflicts of interest Dr. Szmuilowicz reported that she was previously a sub-investigator in a clinical trial of a diabetes treatment (GLP-1 agonist) sponsored by Sanofi-aventis, and she received no financial compensation. Dr. Seely reported that she received a Bayer Health Care investigator-initiated grant. Dr. Howard reports: consultant for Merck/Schering-Plough; research support from donation of drugs from Merck/Shering-Plough; lectures for Merck/Schering-Plough. None of the other authors reported financial disclosures. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptMenopause. Author manuscript; available in PMC 2012 June 1. Conclusions-Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with onset of VMS at different stages of menopause.Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from classical perimenopausal VMS.

This study is an evaluation of surgical treatment for vulvar vestibulitis, a major cause of superficial dyspareunia in premenopausal women. Its estimated prevalence in a general gynecologic population is 15%. Those affected have severe vestibular pain on touch or vaginal entry as well as tenderness to pressure within the vulvar vestibule. It is not uncommon for symptoms to last longer than 6 months with no apparent cause. The investigators reviewed the records of 155 women 40 years of age or younger who were operated on for this condition in the years 1998 through 2001. Just over 80% of these women (n ϭ 126) were interviewed by telephone 1 to 4 years postoperatively.A single gynecologist performed all operations in a uniform manner under general anesthesia on an outpatient or short-admission setting. Vestibulectomy and advancement plasty are carried out. The procedure entails total removal of the hymen and the full thickness of skin on the adjacent vestibulum (Hart's line and the fourchette are boundaries). The remaining defect is covered by vaginal wall after it has been undermined and advanced. Vaginal dilation exercises with a mold begin 6 weeks postoperatively if wound healing is satisfactory; at the same time, women are encouraged to begin or resume intercourse.The phone interview, carried out a median of 37 months after surgery, revealed that 93% of women were able to have intercourse and that 62% had no pain in doing do. Just over 60% of women had no postoperative complications. The most common problem, affecting approximately one fourth of patients, was decreased lubrication during sexual arousal. Eight patients (6%) developed a Bartholin's cyst. The odds ratio (OR) for being able to have intercourse only after surgery was 3.43 (95% confidence interval [CI], 1.48-7.96). For women 30 years of age or younger, the OR was 8.20 (95% CI, 1.54-43.73). Younger women were especially disposed to suggest the procedure to other patients. The results were basically the same after adjusting ORs for the follow-up interval. The outcome of surgery could not be related to parity, the ability to have intercourse before surgery, or previous nonsurgical treatment.Surgery has a role in the management of vulvar vestibulitis syndrome; and, because there is a low risk of surgical complications, it can be presented as a potentially helpful option when medical measures have proved not to be effective. GYNECOLOGYVolume 61, Number 6 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACT Although laparoscopic myomectomy (LM) provides a minimally invasive alternative to laparotomy for removing intramural and subserosal uterine myomas, even experienced surgeons occasionally have to convert to an open procedure. Dubuisson and coworkers have developed a model predicting the need for laparoconversion (LC) based on 4 independent risk factors: size, type, and site of the dominant myoma, and pretreatment with a gonadotropin-releasing hormone agonist. The investigators sought to identify preoperative factors that influence the need for LC in 116 women ...

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We studied the kinetics and metabolism of tritiated 5 alpha-androstane-3 alpha-17 beta-diol glucuronide (3 alpha diolG) in normal and hirsute women. We found no difference in the MCR of 3 alpha diolG between normal and hirsute women [130 +/- 39 (+/- SD) vs. 157 +/- 81; P = NS]. The blood production rate was markedly increased in hirsute women (187 +/- 50 vs. 604 +/- 355 micrograms/day; P less than 0.001) and correlated well with the plasma 3 alpha diolG level (r = 0.96). In women, the conversion ratio of 3 alpha diolG to unconjugated 3 alpha diol or dihydrotestosterone was less than 1%, while the conversion ratio to dihydrotestosterone glucuronide was about 6%. We conclude that the elevated plasma levels of 3 alpha diolG characteristic of hirsutism reflect increased production of this androgen metabolite.