David H. Barad

The Women's Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants.

The postmenopausal hormone therapy (PHT) component of the Women’s Health Initiative (WHI) is composed of two randomized, placebo-controlled, double-blind trials in postmenopausal women aged 50 to 79 years at initial screening, testing the effects of estrogen alone (E-alone) and estrogen plus progestin (E P) on coronary heart disease (CHD) as the primary outcome, hip and other fractures and colorectal cancer as secondary outcomes, and pulmonary embolism, breast and endometrial cancers as potential risks. The design and rationale of the PHT trials, including general eligibility and exclusion criteria and considerations regarding sample size and statistical power, have been described previously (1). Postmenopausal hormones have been initiated in menopausal women for the treatment of vasomotor symptoms, mood disturbances, vaginal dryness, and prevention of rapid bone loss for several decades. Despite a paucity of data on effects of initiating hormone use in older women, postmenopausal hormones have also been promoted for the prevention of CHD, osteoporotic fractures, and other diseases that occur years after menopause (2). It is generally recommended (2) that women with a uterus be prescribed a combination of estrogen and progestin to prevent endometrial

Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative

Objective:The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Womens Health Initiative (WHI). Methods:Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. Results:Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). Conclusions:Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.

Association of pelvic organ prolapse and fractures in postmenopausal women: analysis of baseline data from the Women's Health Initiative Estrogen Plus Progestin trial.

Objective: Testing a hypothesis that pelvic organ prolapse (POP) is a focal manifestation of disordered connective tissue, we evaluated whether there is an association between POP and history of fracture. Design: This was a case-control study. Baseline data were from postmenopausal women aged 60 years or older enrolled in the Womens Health Initiative Estrogen Plus Progestin trial. Distinct variants (cystocele, rectocele, and uterovaginal) and severity (mild, moderate, or severe) of POP were recognized. A history of fracture after age 55 was considered as the event of interest. Results: Moderate to severe POP was identified in 9% of 11,096 participants aged 60 years or older. Women with moderate to severe rectocele were significantly more likely to report fracture (odds ratio: 1.37, 95% CI: 1.06-1.77, P = 0.02) compared with those with absent to mild prolapse. Of the subset of participants who underwent bone mineral density assessment, those with moderate to severe prolapse demonstrated significantly lower whole-body bone mineral density (&bgr; = −0.03, SE 0.02); this difference was of borderline significance (P = 0.05) compared with that for participants with absent to mild POP. Multivariate logistic regression analysis confirmed an independent association between moderate to severe rectocele and fracture (odds ratio: 1.45, 95% CI: 1.08-1.95, P = 0.01). Conclusions: We demonstrate a relationship between moderate to severe POP and low bone mineral density in postmenopausal women enrolled in the Womens Health Initiative Estrogen Plus Progestin trial. Our findings of an association between clinically significant (moderate to severe) POP, specifically rectocele, and a history of fracture suggest that suboptimal collagen status purported to associate with POP may also involve bone collagen and hence translate into skeletal compromise.

Relative Effects of Tamoxifen, Raloxifene, and Conjugated Equine Estrogens on Cognition

OBJECTIVEnTo compare the relative effects of conjugated equine estrogens (CEE), raloxifene, and tamoxifen therapies on cognition among women aged > or =65 years.nnnMETHODSnAnnual Modified Mini-Mental State (3MS) examinations were used to assess global cognitive function in the two randomized placebo-controlled clinical trials of CEE therapies of the Womens Health Initiative Memory Study (WHIMS) and the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were limited to women who had 3MS testing at baseline and the first 3 years of follow-up and, because of potential ethnic-related differences between studies, to Caucasian women (WHIMS n = 6211, CoSTAR n = 250). Covariate adjustment was used to compare the postrandomization mean 3MS scores among the three active therapies with placebo therapy while controlling for differences between groups with respect to dementia risk factors.nnnRESULTSnAt baseline, the average (SD) 3MS scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE, 94.60 (4.76) for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each active therapy was associated with a small mean relative deficit in 3MS scores of < or =0.5 units, which was fairly consistent between women with and without prior hysterectomy. Relative deficits were slightly greater for tamoxifen (p = 0.001) and less marked for raloxifene (p = 0.06) and CEE (p = 0.02) therapies. Relative deficits appeared to be greater among women with lower baseline 3MS scores: p = 0.009 (tamoxifen), p = 0.08 (raloxifene), and p = 0.03 (CEE).nnnCONCLUSIONSnAlthough unmeasured differences between trials may have confounded analyses, these findings raise the possibility that both tamoxifen and raloxifene adversely affect cognitive function in older women; however, the magnitude of the effect is small, and the long-term consequences are unknown.

Effects of Smoking on the Levels of Antioxidant Beta Carotene, Alpha Tocopherol and Retinol in Human Ovarian Follicular Fluid

The concentrations of beta-carotene, retinol and alpha-tocopherol were measured by high-pressure liquid chromatography in ovarian follicular fluid and plasma samples collected at the time of oocyte recovery from patients enrolled in our in vitro fertilization program. The mean beta-carotene levels in follicular fluid [0.182 +/- (SEM) 0.04 nmol/ml] and plasma (0.37 +/- 0.34 mmol/ml) of smokers (n = 5) were significantly (p < 0.025 and p < 0.001, respectively) lower compared with the mean levels in follicular fluid (0.58 +/- 0.10 nmol/ml) and plasma (1.11 +/- 0.09 mmol/ml) in nonsmokers (n = 11). The follicular fluid and plasma retinol and alpha-tocopherol levels were comparable among the nonsmokers and smokers. These findings direct attention to a possible role of the antioxidant beta-carotene, per se, as a biological marker in ovarian oocyte follicular maturation and function.