Biomedical subjects
Publications and source records attributed to L Speroff.
Because randomized trials of the impact of hormone therapy on women's health are lacking, clinicians can only point out the benefits established in observational studies, discuss the potential risks, and allow each patient to decide for herself. Informed decision making is time-consuming, however. Ample educational materials and a counselor may facilitate the process.
To compare the clinical performance of the TCu380A, the most widely used copper IUD in the world today, and a new frameless device, the Cu-Fix, we report results from a randomized international two-year clinical trial involving 874 parous women followed for an average of fourteen months. Event rates at the end of two years (per 100 women) for pregnancy were 0.0 for the TCu380A and 1.5 for the Cu-Fix. Termination due to expulsion was significantly less for TCu380A as compared with Cu-Fix users (2.0 and 11.4 per hundred women, respectively); other medical reasons for termination (bleeding/pain, pelvic inflammatory disease (PID), and other) did not differ significantly. PID incidence rates at two years were 1.0 per hundred women for the TCu380A and 1.6 for the Cu-Fix (equivalent to 6.0 and 8.3 per 1,000 woman-years, respectively). The net cumulative continuation rates at two years per hundred women were 78.8 for TCu380A, and 71.9 for the Cu-Fix. Both IUDs provide highly effective protection against pregnancy, but the TCu380A has a lower expulsion rate. The low rate of PID indicates that it is an in-frequent occurrence in appropriately selected candidates.
In October, 1995, the United Kingdom Committee on Safety of Medicines recommended that women should use oral contraceptives containing desogestrel or gestodene only if prepared to accept an increased risk of thromboembolism. This action was based on observational studies that indicated a 2-3-fold increase in the risk of thromboembolism when desogestrel and gestodene-containing contraceptives were compared to products with levonorgestrel. The fact that these studies point in the same direction is concerning, but it is possible that these observational studies, somewhat similar in design, are influenced by the same unrecognized biases. Furthermore, the case numbers are relatively small (20-40 cases), and, for example, preferential prescribing to women at greater risk could affect the results. It is difficult to reconcile the conclusions with the strong belief supported by good evidence that thrombosis is an estrogen dose-related complication, and that progestational agents have no impact on clotting parameters. In my view, these equivocal reports are not of sufficient strength to escape biases and to change our prescribing of oral contraceptives.
Given the magnitude of the older female population, the possibility that postmenopausal hormone therapy is associated with an increased risk of breast cancer is an issue of great public and individual importance. Epidemiologic evidence indicates the possibility of a slightly increased risk of breast cancer associated with long durations of postmenopausal estrogen use. However, in a review of the literature, it is apparent that the epidemiologic data are contradictory and do not yield uniform and consistent results. It is further apparent that adding a progestin to a postmenopausal hormone program does not alter the findings compared with the use of estrogen alone. Reasons for this disagreement and lack of definitive evidence are detailed, and it is suggested that any impact of postmenopausal hormone therapy on the risk of breast cancer is unlikely to be great. Finally, the question of whether a woman who has had breast cancer should use postmenopausal hormones is addressed.
OBJECTIVE: To determine the efficacy and local tolerance of a new matrix transdermal drug-delivery system that delivers 0.02 mg of 17 beta-estradiol (E2) daily for 7 days for the relief of vasomotor symptoms. METHODS: A total of 324 surgically or naturally menopausal women, all with prior hysterectomy and moderate to severe vasomotor symptoms (56-140 hot flushes per week, with episodes of sweating, during a baseline observation period), participated in two independent, 12-week, randomized, double-blind, placebo-controlled studies. After a 4-week, treatment-free period, each woman received a continuous regimen of either one E2 transdermal system, two E2 transdermal systems, or placebo transdermal system(s) applied every week for 12 weeks. Efficacy was measured as reduction in hot flush frequency, determined from subject diaries. To measure local tolerance, skin irritation (erythema and edema) was objectively and systematically evaluated under blue light after removal of the transdermal system(s). Serum E2 and estrone concentrations were determined in one of the studies during baseline and on days 1, 9, 30, 58, 79, and 84. RESULTS: Mean hot flush frequency decreased from 80 hot flushes per week at baseline to approximately 13 hot flushes per week (84% decrease) after 12 weeks of transdermal E2 treatment. Compared with placebo, the decrease in hot flush frequency was significant as early as weeks 2 and 3, and was maintained through the end of the study. Few clinically significant skin reactions occurred, and only nine (3%) of the subjects withdrew because of a skin effect. After initial increase, serum E2 concentrations remained stable throughout the study, achieving values of approximately 20 and 40 pg/mL above baseline for one and two E2 transdermal systems, respectively. CONCLUSION: The E2 transdermal system effectively reduced the frequency of moderate to severe vasomotor symptoms as early as the second week of therapy and was very well tolerated. The decrease in hot flush frequency was similar to that reported for oral and other transdermal estrogens, but at lower serum E2 concentrations. This result may be due to the stable E2 blood level achieved with this transdermal system.
OBJECTIVE: Our purpose was to determine whether sex steroids alter aortic size and compliance in postmenopausal women. STUDY DESIGN: Twenty-six postmenopausal women were randomized to receive either conjugated estrogens 0.625 mg per day (group 1) or conjugated estrogens 0.625 mg per day and medroxyprogesterone 2.5 mg per day (group 2). Aortic cross-sectional area was measured by magnetic resonance imaging before and after 3 months of hormone therapy. RESULTS: Estradiol levels increased in both group 1 and group 2 (p < 0.0001). Ascending aortic cross-sectional area increased from 439 +/- 7 mm2 to 466 +/- 7 mm2 in group 1 (p < 0.008) but was unchanged in group 2. Within the range of aortic pressures studied, no change in aortic compliance could be detected. CONCLUSION: Estrogen therapy in postmenopausal women was associated with an increase in aortic size; but this effect was not detectable with the addition of progestin. The potential antagonistic effect of progestin on estrogen-induced aortic enlargement suggests that the favorable cardiovascular effects of postmenopausal estrogen therapy cannot be automatically extended to the combination estrogen-progestin.
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In the developed world, deferment of marriage and postponement of child-bearing in marriage are resulting in unprecedented numbers of couples who desire pregnancy relatively late in life. These factors combine with a decline in fertility and an increase in pregnancy wastage with advancing age to present new challenges for the clinician treating infertility. Experience with young oocytes donated to older women indicates that the major responsibility for the decline in fertility with age can be attributed to aging oocytes. Oocyte donation offers new hope for infertile older woman, but important moral and social questions remain unanswered.
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OBJECTIVE: To compare the efficacy and safety of esterified estrogens with and without methyltestosterone. METHODS: Twenty-six women participated in a double-blind randomized trial for 6 months. Outcome measures included serum total and lipoprotein-bound cholesterol, vasomotor symptoms, vaginal cytology and endometrial histology, and chemistry values. Analysis of variance and t test statistics were used to assess differences. RESULTS: After 6 months of therapy, the treatment groups were comparable with regard to symptom scores, vaginal cytology and endometrial histology scores, and clinical laboratory test values. Treatment with esterified estrogens plus methyltestosterone significantly decreased total cholesterol, high-density lipoprotein cholesterol (HDL), HDL2, HDL3, and apolipoprotein A1 compared to esterified estrogens alone. CONCLUSIONS: Esterified estrogens with or without methyltestosterone were effective at reducing menopausal symptoms and were well tolerated over 6 months of continuous treatment. A significant decrease in cholesterol and apolipoproteins in the estrogen plus methyltestosterone group suggests a potentially adverse impact on the beneficial effect normally imparted by estrogen therapy.
The beneficial impact of hormone replacement therapy on postmenopausal women is substantial. The size of the positive impact has probably been underestimated owing to compliance issues. Patients and physicians need to learn about the important contribution to preventive health care that occurs with estrogen. Negative beliefs about menopause by both patients and physicians may contribute to poor compliance with hormone replacement therapy. It is time to emphasize the positive aspects: the prospect for long life made healthy by a good preventive care program.
OBJECTIVE: To assess the differences and similarities in efficacy, safety, and metabolic effects of oral contraceptives (OCs) containing the new progestins desogestrel, gestodene, and norgestimate. All formulations reviewed contained no more than 35 micrograms ethinyl estradiol. DATA SOURCES: Data were reported from approximately 100 published reports, dating from 1980, of comparative and noncomparative clinical studies on phasic and fixed-dose preparations culled from computer searches of several sources, including MEDLINE and Excerpta Medica. METHODS OF STUDY SELECTION: An attempt was made to select the most meaningful studies in terms of length, size, methodology, and quality of description. All clinical studies were considered; in general, review articles were not. Some preclinical studies were also included. No abstracts were used. DATA EXTRACTION AND SYNTHESIS: The indices chosen for examination were contraceptive efficacy, cycle control, coagulation, carbohydrate and lipid metabolism, and androgenicity. CONCLUSIONS: The new formulations were found to be comparable in efficacy to each other and to established agents. They also appeared to be less androgenic than current OCs and to have less impact on carbohydrate and lipoprotein metabolism. Cycle control was similar to that of older products. Changes in coagulation-promoting and antithrombotic factors were minor. Clinical relevance of the results could not be determined because of small sample size and methodologic differences between studies.
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It has been postulated that in polycystic ovary syndrome ovarian steroids can influence adrenal steroidogenesis. To test this hypothesis, basal and dexamethasone-suppressed-corticotropin-stimulated steroid hormone responses were compared among three groups of women before, during, and after gonadotropin-releasing hormone agonist treatment for 3 months. The groups were characterized as follows: (1) women with polycystic ovary syndrome with high dehydroepiandrosterone sulfate levels (greater than 400 micrograms/dl), (2) women with polycystic ovary syndrome with normal dehydroepiandrosterone sulfate levels (less than 300 micrograms/dl), and (3) normal ovulatory women. In response to gonadotropin-releasing hormone agonist, basal serum luteinizing hormone, follicle-stimulating hormone, estradiol, estrone, 17-hydroxyprogesterone, androstenedione, and testosterone in all three groups were suppressed to similar levels. Basal serum dehydroepiandrosterone sulfate levels in the group with high levels declined, but they did not reach the normal, unaltered concentrations in the other two groups. Two subjects with polycystic ovary syndrome in this group with high levels, who showed the greatest declines in basal serum dehydroepiandrosterone sulfate levels (34%, 40%), also had evidence of 3 beta-hydroxysteroid dehydrogenase deficiency before treatment, which was resolved by the end of treatment. In both groups with polycystic ovary syndrome, the increase in maximum incremental rise of dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in response to a pharmacologic dose of corticotropin from a dexamethasone-suppressed baseline (adrenal androgen capacity) remained unaltered during gonadotropin-releasing hormone agonist administration. We conclude that ovarian steroids may promote excessive adrenal androgen secretion in women with polycystic ovary syndrome, may induce 3 beta-hydroxysteroid dehydrogenase deficiency as a mechanism for adrenal involvement in some women with polycystic ovary syndrome, and do not influence adrenal androgen capacity.
A bilateral oophorectomy at the time of elective hysterectomy is often performed to prevent ovarian cancer. The assumption that endogenous estrogen can be easily replaced with supplemental medication fosters the decision for routine oophorectomy. Published reports on the use of postmenopausal estrogen indicate that compliance is less than perfect. This fact could affect the overall outcome. Decision analysis techniques with Markov cohort modeling were used to evaluate the policy of elective bilateral oophorectomy. Results from studies judged methodologically sound were combined to determine values representing the influence of estrogen on coronary heart disease, breast cancer, and osteoporotic fracture. The decision tree also explicitly incorporated patient compliance. When compliance with estrogen therapy is assumed to be perfect, oophorectomy yields longer life expectancy than retaining the ovaries. When actual drug-taking behavior is considered, retaining the ovaries results in longer survival. This analysis highlights the importance of including the effects of patient compliance with treatment recommendations when the impact of a health policy decision such as prophylactic surgery is assessed.
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