Discussion of session on prostaglandins in female reproductive physiology.
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Biomedical subjects
Publications and source records attributed to L Speroff.
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The controversy involving new progestin oral contraceptives (OC) began in late 1995, continued through 1996, and started to reach resolution in 1997. The fundamental question is whether OC containing desogestrel and gestodene have a different risk of thrombosis compared with OC containing older progestins. Correcting for preferential prescribing and the healthy user effect leads to the conclusion that all low-dose OC--regardless of progestin type--have an increased risk of venous thromboembolism. Low-dose OC do not increase the risk of myocardial infarction or stroke in healthy, non-smoking women less than 35 years of age. With effective patient screening for risk factors, the serious side effects of OC can be virtually eliminated.
OBJECTIVE: To determine whether there is a significant reduction in frequency and severity of hot flashes in symptomatic postmenopausal women who are administered continuously different dose combinations of norethindrone acetate and ethinyl estradiol. DESIGN: Two randomized clinical trials (Study 1 and Study 2) were conducted in which study participants recorded in daily diaries the frequency of their hot flashes. Study 2 participants also recorded the number of mild, moderate, or severe hot flashes they experienced. In Study 1, a total of 219 postmenopausal women reporting vasomotor symptoms were placed randomly into groups to receive either a placebo or 1 of 4 treatments (0.2 mg/1 microg; 0.5 mg/2.5 microg; 1 mg/5 microg; or 1 mg/10 microg norethindrone acetate/ethinyl estradiol). In Study 2, a total of 266 highly symptomatic postmenopausal women were placed randomly to receive either a placebo or 1 of 3 treatment groups [0.5 mg/2.5 microg; 1 mg/5 microg; or 1 mg/10 microg norethindrone acetate (NA)/ethinyl estradiol (EE)]. Total duration of treatment was 16 weeks in Study 1 and 12 weeks in Study 2. Study 1 subjects had to have at least 10 hot flashes during the week before randomization. Study 2 subjects had to have at least 56 moderate to severe hot flashes during the week before randomization. RESULTS: In both studies, there was a dose-related decrease in hot flash frequency with the highest dose (1 mg NA/10 microg EE) group that had the greatest response. Significant differences from placebo (p < 0.05, Dunnett's test) occurred within 4 weeks in Study 1 for hot flash frequency with a percent reduction in frequency ranging from 33% for placebo to 84% for both the 1 mg NA/10 microg EE and 1 mg NA/5 microg EE dose groups. Likewise, Study 2 significant reductions in hot flash frequency occurred by Week 2 for 1 mg NA/10 microg EE, Week 3 for 1 mg NA/5 microg EE, and Week 5 for 0.5 mg NA/2.5 microg EE (p < 0.05, Dunnett's test). This dose effect was also apparent with regard to severity. In addition, more subjects had clinically meaningful reductions in hot flash frequency or elimination as the dose combinations increased. CONCLUSION: There were significant reductions in hot flash frequency and severity with continuous treatment with norethindrone acetate and ethinyl estradiol combinations. The time at which significant reductions were observed, as well as the magnitude of the response, were dose dependent. The opportunity for lower-dose options of a new continuous-combined hormone replacement therapy provides therapeutic flexibility for women who are recently menopausal.
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We have encountered the beginning of a new problem: the social challenge is shifting from population control to the consequences of population aging. The older segment of our population is increasing, and it is dominated by women. By age 85, only 45 men are alive for every 100 women. Our best health strategy is to postpone clinical illness by preventive health care. The menopause occurs at a strategic time in life, when preventive health care can have a major impact. The issues of preventive health care for women are familiar ones: family planning, cessation of smoking, prevention of heart disease and osteoporosis, maintenance of mental and sexual well-being, cancer screening and treatment of urologic problems.