Search

INTRODUCTION:Rising health care costs are a major focus today. We examined the costs incurred in pregnant women presenting to a perinatal center to rule out rupture of membranes and the potential savings that would have occurred if this condition 1) could have been assessed at home or 2) inexpensive

This article describes an interim safety analysis of an ongoing 2-year, double-blind study to compare two doses of estrogen-androgen therapy (0.625 or 1.25 mg esterified estrogens combined with 1.25 mg or 2.5 mg methyltestosterone, respectively) with two doses of conjugated estrogens (0.625 mg or 1.25 mg conjugated equine estrogens) in 291 surgically menopausal women. Except for an excess of nausea in the estrogen-only group, reported adverse events (headache, breast pain, weight increase, vaginitis, and hirsutism) did not differ significantly between groups. The majority of adverse events were manifest by 6 months and were not dose related. Only four estrogen-androgen and two conjugated estrogen participants reported hirsutism as an adverse event, but Ferriman-Gallwey evaluations at 12 months detected increased hair growth in 14%–22% of women in each treatment group, with a slight but nonsignificant increment in the higher dose estrogen-androgen group. No significant differences between groups f...

The present study was undertaken to determine whether the addition of an androgen to estrogen therapy in postmenopausal women would alter the skeletal response as determined by measurements of markers of bone formation and resorption. Postmenopausal women were treated for 9 weeks with either a combination of 1.25 mg esterified estrogen and 2.5 mg methyltestosterone (E+A) or 1.25 mg conjugated equine estrogen (CEE). Both groups showed a similar decrease in urinary excretion of the bone resorption markers, deoxypyridinoline, pyridinoline, and hydroxyproline. Patients treated with CEE showed decreases in the serum markers of bone formation, bone-specific alkaline phosphatase, osteocalcin, and C-terminal procollagen peptide. In contrast, subjects treated with E+A showed increases in these markers of bone formation. CEE increased, and E+A decreased serum levels of sex hormone-binding globulin as well as triglycerides and high density lipoprotein levels. Only CEE significantly reduced low density lipoproteins. Both regimens were effective in reducing postmenopausal somatic symptoms, but only E+A had a significant effect on psychological symptoms. We conclude that short term administration of androgen with estrogen may reverse the inhibitory effects of estrogen on bone formation. Long term studies are needed to determine the relative benefits and risks of the combination of estrogen and androgen and whether this results in greater increases in bone mass and strength.

Objective: To determine if women could measure their vaginal pH as accurately as could physicians. Methods: Each participant measured her vaginal pH using a swab, completed a survey, and then was seen by her physician, who also performed a vaginal pH test. The physician did not have access to the patient's pH reading; only the study coordinator recorded patient results. Accuracy of patient measurements compared with physician results was analyzed by the kappa statistic. Results: A total of 161 women were enrolled in the study. The average difference between the patients' pH readings and the physicians' readings was

OBJECTIVE We aimed to find how self-reported sleep (measured by the St. Mary's Hospital Sleep Questionnaire) in postmenopausal women having hot flash activity was related to objective sleep (actigraphy), psychological and somatic symptoms [Women's Health Questionnaire (WHQ)], and cognitive test performance (computerized tests). A secondary aim was to find if self-reported sleep showed expected correlations with hyperarousal (Hyperarousal Scale). DESIGN Drug trial baseline data from 88 healthy, postmenopausal women were retrospectively analyzed. Multivariate regression was used to adjust for confounder variables and test whether differences in self-reported sleep measures were systematically associated with differences in objective sleep, WHQ symptom measures, or cognitive test performance scores. RESULTS Increased self-report scores for low sleep quality were associated with an increased risk of WHQ symptoms and reduced cognitive test performance. Self-reported sleep measures showed little correlation with their analogous objective measures. Self-reported low sleep quality proved most closely associated with the WHQ symptoms of tiredness, clumsiness, and difficulty concentrating. Women whose self-reported sleep-onset latency times were longer than the median overestimated their objective sleep onset time by 30 min, whereas the other women underestimated theirs by 15 min (P < 0.0001). Women whose self-reported total sleep was longer or shorter than the median, respectively, underestimated objective sleep times by 9 and 71 min (P < 0.0001). High hyperarousal scores were associated with underestimations of objective sleep. CONCLUSION Self-reports of lower sleep quality were associated with increased WHQ psychological and somatic symptom measures and decreased cognitive test performance more than with differences in objective sleep. Self-reported trouble sleeping may signal problems independent from objectively low sleep quality, such as subjective distress or diminished cognitive function.

Urinary incontinence affects 11 million women in the United States and is most common in older women. There are several different forms of urinary incontinence, which can be distinguished by their associated pathophysiologic conditions and signs. Genuine stress incontinence is the instantaneous leakage of urine in response to raised intraabdominal pressure associated with such activities as lifting, sneezing, and coughing. Risk factors for development of this form of incontinence include vaginal delivery, vaginal surgery, inadequate estrogen levels, and advanced age. Surgery, the most effective curative treatment for stress incontinence, is invasive and expensive and can lead to impairment of normal urinary tract functions. Other management options include pelvic floor rehabilitation by means of exercise, pharmacotherapy, intravaginal and intraurethral devices, absorbent products, and external occlusive devices.A review of publications on the effectiveness of available external occlusive devices is presented, with special emphasis on a new, single-use, disposable urethral cap device which offers women with stress incontinence an over-the-counter product that enables them to independently manage their incontinence according to their individual needs.Non-surgical methods of managing urinary incontinence are available, with newer methods providing a greater range of choices for women.External occlusive devices can be effectively used by women with urinary incontinence who will not or cannot have surgical correction of the problem.

17alpha-methyl testosterone is a synthetic androgen with affinity for the androgen receptor. 17alpha-methyl testosterone is used widely as a component of hormone replacement therapy. Previous reports have indicated that contrary to testosterone, 17alpha-methyl testosterone is not aromatized. However, 17alpha-methyl testosterone still could affect local estrogen formation by regulating aromatase expression or by inhibiting aromatase action. Both possibilities have important clinical implications. To evaluate the effect of 17alpha-methyl testosterone on the expression and activity of aromatase, we tested the choriocarcinoma Jar cell line, a cell line that express high levels of P450 aromatase, and the macrophage-like THP-1 cells, which express aromatase only after undergoing differentiation. We found that in both cell lines, 17alpha-methyl testosterone inhibits aromatase activity in a dose-related manner. The curve of inhibition parallels that of letrozole and gives complete inhibition at 10(-4) M 17alpha-methyl testosterone, determined by the tritium release assay. 17alpha-methyl testosterone does not have detectable effects on aromatase RNA and protein expression by Jar cells. Undifferentiated THP-1 cells had no aromatase activity and showed no effect of 17alpha-methyl testosterone, but differentiated THP-1 (macrophage-like) cells had a similar inhibition of aromatase activity by 17alpha-methyl testosterone to that seen in Jar cells. The Lineweaver-Burke plot shows 17alpha-methyl testosterone to be a competitive aromatase inhibitor. Our results show for the first time that 17alpha-methyl testosterone acts as an aromatase inhibitor. These findings are relevant for understanding the effects of 17alpha-methyl testosterone as a component of hormone replacement therapy. 17alpha-methyl testosterone may, as a functional androgen and orally active steroidal inhibitor of endogenous estrogen production, also offer special possibilities for the prevention/treatment of hormone-sensitive cancers.

A cross-sectional survey was conducted to examine quality of life (QOL) related to physiological, somatic, and vasomotor effects of changing progestogen treatment from medroxyprogesterone acetate (MPA) to micronized progesterone in postmenopausal women. Eligible women (n = 176) were currently using hormone replacement therapy (HRT) containing micronized progesterone for 1-6 months and had previously received HRT containing MPA. QOL was assessed via telephone interview using the Greene Climacteric Scale and the Women's Health Questionnaire. When compared with the MPA-containing regimen, women using micronized progesterone-containing HRT experienced significant improvement in vasomotor symptoms, somatic complaints, and anxiety and depressive symptoms. Women reported improved perceptions of their patterns of vaginal bleeding and control of menopausal symptoms while on the micronized progesterone-containing regimen. Approximately 80% of women reported overall satisfaction with the micronized progesterone-containing regimen. A micronized progesterone-containing HRT regimen offers the potential for improved QOL as measured by improvement of menopause-associated symptoms.

The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder).In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of "much improved" or "very much improved" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale.The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe.These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia.

Objective: To compare the effects of estrogen with estrogen-androgen treatment on vaginal blood flow velocity and fingertip postocclusive hyperemic blood flow response. Design: Prospective, randomized, parallel, double-blind study. Setting: Healthy human volunteers in an academic research environment. Patient(s): Postmenopausal women receiving estrogen replacement therapy for at least 12 months and treated with placebo before this investigation. Intervention(s): Esterified estrogens or esterified estrogen + methyltestosterone were administered orally; laser Doppler velocimetry was used to determine vaginal and fingertip blood flow responses at baseline and after 4 and 8 weeks of daily drug administration. Main Outcome Measure(s): Fingertip postocclusive area under curve (AUC); vaginal blood flow velocities. Result(s): The AUC for postocclusive fingertip blood flow and vaginal blood flow increased to a greater extent in the estrogen-androgen group, but changes were not statistically significant between groups. Conclusion(s): Estrogen-androgen treatment does not diminish the vasodilator effects of estrogen treatment in postmenopausal women.

The endocrine physiology of the climacteric supports a rationale for the concomitant replacement of androgen and estrogen following menopause. Clinical and research experience with estrogen-androgen hormone replacement therapy, as well as androgen-only therapy, suggests that the health benefit offered by androgen replacement exceeds the potential risk when treatment is properly managed. In this review, we concentrate on the effects of oral alkylated androgens. The virilizing effects (e.g., hirsutism, acne, voice change, and alopecia) of oral androgens are typically dose and duration dependent; androgen replacement at dosesor = 10 mg once daily administered for prolonged periods (6 months) produces masculinization effects that generally abate with dose reduction or discontinuation of treatment. No clinical sequelae or irreversible pathophysiologic effects have been associated with any virilization that may occur. Changes in lipoprotein metabolism associated with oral estrogen-androgen use include reduced total cholesterol levels and reduced high-density lipoprotein cholesterol levels which may reduce the long-term risk of cardiovascular disease. No clinically identifiable risk with respect to other cardiovascular variables, such as blood pressure, has been associated with the longterm administration of low doses of oral androgen. With regard to liver toxicity, reports of jaundice, peliosis hepatis, and hepatocellular carcinoma are extremely rare at the dose levels of androgen used in hormone replacement therapy, although individual sensitivity to the potential hepatotoxic effects of oral alkylated and nonalkylated androgen may vary considerably. Daily dosing with oral alkylated androgen in combination with estrogen is well tolerated. Retrospective and prospective studies involving the use of androgens alone and in combination with estrogens demonstrate that concerns about the adverse effects of androgen use associated with supraphysiologic, self-escalated doses in men do not apply to the much lower doses combined with estrogens for hormone replacement in postmenopausal women.

Although both epidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of coronary heart disease, the mechanisms for this beneficial effect are largely unknown. Furthermore, the addition of progestins or androgens to estrogen replacement therapy is of concern. The objective of this study was to examine the effects of esterified estrogens alone or in combination with an androgen on arterial LDL metabolism and early atherogenesis in ovariectomized female cynomolgus monkeys. Arterial LDL metabolism was assessed by using dual-labeled LDL that was injected 24 hours before necropsy. Arterial LDL degradation was reduced by 64% to 84% and cholesteryl ester content was decreased by ≈50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lipid peroxidation products, as assessed by thiobarbituric acid reaction, were significantly lower in animals treated with esterified estrogens, with a similar trend for combined estrogen-androgen treatment. Both treatments also reduced plasma concentrations of apoB-containing lipoproteins, reduced LDL particle size, and increased total-body LDL catabolism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metabolism may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combination of estrogen and androgen.

We measured the relative binding affinity (RBA) of 17-alpha-methyltestosterone (MET) for the rat prostate androgen receptor and human sex hormone-binding globulin (SHBG) in vitro. The reference compound in both instances was dihydrotestosterone (DHT), the RBA of which was set at 100%. The RBA of methyltestosterone was 44% for the androgen receptor, but 11% for SHBG. The androgen receptor, therefore, would appear to recognize a different part of an androgen compared to the recognition site on SHBG. The difference in RBAs may amplify the biologic action of methyltestosterone.

OBJECTIVE To investigate somatic symptom relief, gonadotropin secretion, and endogenous androgen bioavailability (protein-bound and free) during 3 months of estrogen-androgen therapy or matched estrogen-only replacement therapy. DESIGN Ninety-three naturally menopausal outpatients with 6 or more months of amenorrhea, who were experiencing mild-to-moderate vasomotor symptoms, were randomized to receive one of five treatments: oral esterified estrogens (0.625 mg or 1.25 mg), oral esterified estrogens combined with methyltestosterone (0.625 mg combined with 1.25 mg methyltestosterone or esterified estrogens 1.25 mg combined with 2.5 mg methyltestosterone), or placebo for 12 weeks. All treatments were preceded by a 4-week placebo lead-in period. RESULTS Patients receiving the lower dose of estrogen-androgen therapy had fewer somatic menopausal symptoms than patients receiving the lower dose estrogen (0.625 mg), and they experienced somatic symptom relief similar to those patients receiving the higher dose of estrogen (1.25 mg). Significantly greater luteinizing hormone suppression (p < or = 0.03) occurred in estrogen-androgen groups compared to estrogen groups, suggesting that added androgen might mediate a more pronounced negative feedback on the hypothalamic-pituitary axis. Sex hormone-binding globulin increased significantly in both estrogen-treated groups (p < or = 0.01), whereas decreases occurred in both estrogen-androgen groups (p < or = 0.006). The higher dose estrogen-only preparation significantly reduced androstenedione (p < or = 0.01) and dehydroepiandrosterone sulfate (p < or = 0.005). CONCLUSION The extent of relief with lower dose estrogen-androgen therapy was similar to higher dose estrogen-only treatment. The greater efficacy of combination therapy on somatic symptoms could be mediated by the same mechanism responsible for the suppressive effects of estrogen-androgen therapy on luteinizing hormone secretion. The marked differences in circulating levels of sex hormone building globulin, which were increased by estrogen and decreased by estrogen-androgen, and the resulting impact on bioavailable androgens and estrogens could also explain the differential somatic relief with both treatments. Endogenous adrenal androgens were lower in women treated with esterified estrogens 1.25 mg/day, suggesting that estrogen therapy can produce a significant hypoandrogenic state by inhibiting production or accelerating clearance of adrenal androgens.

This double-blind comparison of oral conjugated estrogens combined with cyclical dydrogesterone or medroxyprogesterone acetate was conducted in postmenopausal women. In this 1-year, double-blind, randomized, parallel-group, multicenter study, 41 postmenopausal women received 0.625 mg/day of conjugated estrogens plus 10 mg/day of dydrogesterone for 14 days/cycle; and 36 received 0.625 mg of conjugated estrogens plus 10 mg/day of medroxyprogesterone acetate for 14 days/cycle. Changes in lipid and lipoprotein parameters (predictive of reduced cardiovascular risk) were significantly greater in patients receiving 0.625 mg of conjugated estrogens plus 10 mg of dydrogesterone. Dydrogesterone had no adverse impact on glucose tolerance, but circulating glucose levels significantly increased in patients receiving 0.625 mg of conjugated estrogens plus 10 mg of medroxyprogesterone acetate after glucose tolerance testing. Patients receiving conjugated estrogens (0.625 mg) plus dydrogesterone (10 mg) had significantly fewer days with bleeding (51.90 ± 27.52 days) and reduced duration of bleeding episodes (5.56 ± .24 days) than patients receiving conjugated estrogens (0.625 mg) plus medroxyprogesterone acetate (10 mg) (71.40 ±29.63 and 6.74 ± 1.91 days, respectively). Both regimens provided good endometrial protection and relieved somatic, psychosomatic, and psychological menopausal symptoms. Adverse events, vital signs, and clinical laboratory findings were similar for both groups. In combination with conjugated estrogens, dydrogesterone induced a better cardiovascular risk factor profile and induced less vaginal bleeding than medroxyprogesterone acetate.