Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To determine the safety and efficacy of an oral soy isoflavone extract for relief of menopausal hot flushes. DESIGN: This was a double-blind, randomized, parallel group, outpatient, multicenter (15 sites) study. A total of 177 postmenopausal women (mean age = 55 years) who were experiencing five or more hot flushes per day were randomized to receive either soy isoflavone extract (total of 50 mg genistin and daidzin per day) or placebo. Physical examinations and endometrial and biochemical evaluations were performed upon admission and completion. Body weight, symptoms, and safety were evaluated at all visits. RESULTS: Relief of vasomotor symptoms was observed in both groups. Decreases in the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy group, whereas the placebo group experienced no relief for the first 4 weeks. Differences between evaluable subjects in both groups were statistically significant over 6 weeks (p = 0.03). Over 12 weeks, between-group differences approached significance (p = 0.08). Endometrial thickness evaluated by ultrasound, lipoproteins, bone markers, sex hormone-binding globulin and follicle-stimulating hormone, and vaginal cytology did not change in either group. CONCLUSIONS: Soy isoflavone extract was effective in reducing frequency and severity of flushes and did not stimulate the endometrium. Soy isoflavone extracts provide an attractive addition to the choices available for relief of hot flushes.

Single-dose miconazole nitrate vaginal ovule in the treatment of vulvovaginal candidiasis: two single-blind, controlled studies versus miconazole nitrate 100 mg cream for 7 days.

To determine the efficacy and safety of a single-dose (1200 mg) soft gel insert (vaginal ovule) with miconazole nitrate (2%) topical cream compared with Monistat 7 (miconazole nitrate 2%) Vaginal Cream (Advanced Care Products, North Brunswick NJ) in treating vulvovaginal candidiasis (VVC), two randomized, single-blind, multicenter, controlled, comparative phase III studies were performed. Five hundred fifty-eight patients received either a single-dose miconazole nitrate (1200 mg) ovule or seven consecutive doses of Monistat 7. Ovule arm patients also received miconazole nitrate 2% cream for symptom relief, as needed, up to twice daily. The primary end point was a therapeutic cure. Also evaluated were time to complete symptom relief, safety, and patient preference. The ovule had overall cure rates of 71.7% (71 of 99 patients) and 61.5% (64 of 104 patients). Monistat 7 had overall cure rates of 70.1% (68 of 97 patients) and 61.1% (55 of 90 patients). A significantly greater proportion of patients experienced complete symptom relief by day 3 with the ovule (p = 0.008 and p = 0.025), and time to complete relief was significantly faster (median 4 versus 5 days and 3 versus 4 days). Overall safety results were consistent between groups in both studies. Miconazole nitrate vaginal ovule is as safe and efficacious in curing VVC as Monistat 7 while providing complete symptom relief significantly faster. Patients preferred the ovule to prior therapy.

Collaboration with academia in the development of vaginal microbicides.

Advanced Care Products has been active in the development of vaginal microbicides, with public sector support. Currently, nonoxynol-9 gel is being evaluated in two Phase-III studies. Work has been conducted on polystyrene sulfonate, with the aim of filing an investigational new drug application (IND) in the USA. This paper discusses the challenges in development of an over-the-counter (OTC) product for the USA. Public sector support has been pivotal in the progress shown to date. Further challenges lie ahead, vis-à-vis an OTC approval.

Comparison of endometrial growth produced by unopposed conjugated estrogens or by micronized estradiol in postmenopausal women.

OBJECTIVE: When unopposed estrogen replacement treatment is used, what is the pattern of endometrial growth? Does endometrial growth differ for various dosages and formulations? STUDY DESIGN: A total of 87 postmenopausal women, median age 57 years (mean 56.7 +/- 5.6 years, range 45 to 69 years), were studied in a prospective, randomized, open clinical trial lasting 24 weeks. The treatment arms consisted of micronized estradiol, 0.5 or 1.0 mg (Estrace, Bristol-Myers Squibb, Princeton, N.J.), and conjugated estrogens, 0.625 mg (Premarin, Wyeth-Ayerst, Philadelphia). Endometrial thickness was evaluated by vaginal probe ultrasonography at outset and after 6, 12, and 24 weeks of treatment. RESULTS: Endometrial growth was progressive over time; more than half the total 24-week growth occurred in the first 6 weeks. The mean weekly rate (+/-SD) of endometrial growth was similar for micronized estradiol, 1.0 mg, and conjugated estrogens, 0.625 mg (0.19 +/- 0.15 mm for micronized estradiol, 1.0 mg, and 0.19 +/- 0.14 mm for conjugated estrogens, 0.625 mg). These rates differed to a statistically significant degree (p < 0.05) from the growth rate produced by micronized estradiol, 0.5 mg (0.08 +/- 0.16 mm). Both unscheduled and scheduled uterine bleeding was less likely among women using micronized estradiol, 0.5 mg, than among women using micronized estradiol, 1.0 mg, or conjugated estrogens, 0.625 mg. CONCLUSIONS: In a 24-week trial the therapeutically equivalent estrogen doses produced the same mean increment in endometrial thickness, but half-strength estradiol produced half as much endometrial growth.