Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy

Urogenital infections in postmenopausal women remain problematic. The use of estrogen replacement therapy has been shown to lower these infection rates, corresponding to increasing colonization by Lactobacillus species. Despite the gut's 500 microbial species and the proximity of the anus to the vagina, only a relatively few microbial strains appear to be able to colonize the urogenital area. In the present study, the sparsity of microbes in the vagina was confirmed by denaturing gradient gel electrophoresis analysis of swabs taken at time zero and monthly for 3 months from 40 postmenopausal subjects receiving Premarin (conjugated equine estrogen in combination with progesterone) hormone replacement therapy (HRT) and 20 who were not on HRT. Lactobacilli were recovered from the vagina of 95% or more women in both groups, but in the HRT group, Lactobacillus were more often the dominant and only colonizers and significantly fewer bacteria with pathogenic potential were found. The incidence of bacterial vaginosis was significantly lower in the HRT group than in the non-HRT-treated women (5.6% versus 31%). The use of HRTs has recently come under criticism. The ability of drugs such as Premarin to help recover the lactobacilli vaginal microbiota appears to be at least one benefit of HRT use. In women not using HRTs, use of probiotics may be the only way to restore a nonpathogen-dominated flora.     

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women

Brooks, E. M., A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O'Gorman, J. A. Derr, and W. L. Kenney. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J. Appl.Physiol. 83(2): 477-484, 1997.This investigationexamined effects of chronic (2 yr) hormone replacement therapy (HRT),both estrogen replacement therapy (ERT) and estrogen plus progesteronetherapy (E+P), on core temperature and skin blood flow responses ofpostmenopausal women. Twenty-five postmenopausal women [9 not onHRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for1 h at an ambient temperature of 36°C. Cutaneous vascularconductance (CVC) was monitored by laser-Doppler flowmetry, and forearmvascular conductance (FVC) was measured by using venous occlusionplethysmography. Iontophoresis of bretylium tosylate was performedbefore exercise to block local vasoconstrictor (VC) activity at oneskin site on the forearm. Rectal temperature (T_re) was ~0.5°C lower forthe ERT group (P < 0.01) comparedwith E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (T_b) and CVC:T_b curves were shifted~0.5°C leftward for the ERT group(P < 0.0001). Baseline CVC wassignificantly higher in the ERT group(P < 0.05), but there was nointeraction between bretylium treatment and groups once exercise wasinitiated. These results suggest that1) chronic ERT likely acts centrally to decrease T_re,2) ERT lowers theT_re at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition ofexogenous progestins in HRT effectively blocks these effects.

     

Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women

Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body temperature (T(b)) at a lower level than women not receiving hormone replacement therapy (untreated) and women using estrogen plus progesterone therapy (E + P), but it is not clear if reproductive hormones alter T(b) by directly acting on central thermoregulatory centers or indirectly via a secondary mediator(s). The purpose of the present investigation was to examine the possible involvement of pyrogenic cytokines and cyclooxygenase (COX) products (e.g., prostaglandins) in the regulation of T(b) in three groups of postmenopausal women (8 ERT, 7 E + P, and 8 untreated). We measured ex vivo secretion of cytokine agonists [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and -6] and modifiers (IL-2 soluble receptor, IL-1 receptor antagonist, soluble TNF receptor type I, soluble TNF receptor type II, soluble IL-6 receptor, and soluble glycoprotein 130) from peripheral blood mononuclear cells and thermoregulatory responses at rest and during 1 h of passive whole body heating in the postmenopausal women before and after 3 days of placebo or aspirin (50 mg. day(-1). kg(-1)). With and without aspirin, the ERT group had a lower baseline rectal temperature (T(re); 0.44 degrees C, P < 0.004) and a reduced T(b) threshold for cutaneous vasodilation (0.29 degrees C and 0.38 degrees C, P < 0.01) compared with the untreated and E + P groups, respectively. In the placebo condition, waking morning oral temperature (T(or)) correlated with ex vivo secretion of the proteins associated with IL-6 bioactivity. Aspirin caused significant reductions in waking T(or) in the E + P group and in baseline T(re) in the untreated group. However, the difference in thermoregulation brought about by steroid hormone treatment could not be explained by these relatively modest apparent influences by cytokines and COX products. Therefore, the altered thermoregulation induced by reproductive steroid therapy appears to occur via a mechanism distinct from a classic infection-induced fever.     

Effect of postmenopausal hormone replacement therapy on lipoprotein and homocysteine levels in Chinese women

Epidemiological studies have revealed that postmenopausal estrogen replacement therapy results in a marked reduction in the risk for cardiovascular diseases. In the present study, we evaluated plasma lipoprotein profile as well as homocysteine levels in 145 postmenopausal and premenopausal Chinese women living in Hong Kong. We also investigated the effect of hormonereplacement therapy (HRT) with estrogen or estrogen combined with progestin on plasma lipoprotein profile and homocysteine concentrations in those individuals. Postmenopausal women displayed significantly higher plasma levels of total cholesterol, LDLcholesterol and apoB as well as higher plasma homocysteine levels than that of premenopausal women. HRT with either estrogen (17-estradiol or conjugated equine estrogen) alone or estrogen combined with progestin for 3.5–4.5 years significantly improved the lipoprotein profile in postmenopausal women by decreasing the levels of total cholesterol (12–20% reduction), LDL-cholesterol (26–29% reduction) and apoB (21–25% reduction). In women treated with 17estradiol or conjugated equine estrogens their plasma levels of apoAI were significantly elevated (18% elevation) as compared to non-users. HRT also reduced plasma concentrations of homocysteine (13–15% reduction). In conclusion, we found that long-term HRT was associated with improvement in plasma lipoprotein profile and a reduction in homocysteine concentration in postmenopausal women. These results support the notion that the improvement of lipoprotein profile and a reduction in homocysteine concentration may contribute to the beneficial effect of HRT on cardiovascular risk.     

A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy

Recent neurophysiological data suggest that the prefrontal cortex (PFC) may be susceptible to modulation by estrogen. In humans, the PFC mediates a number of cognitive processes that contribute to memory function, particularly working memory. The present study examined whether memory tasks that recruit PFC-dependent information processing might exhibit estrogen sensitivity in women. Performance on several memory tasks, including measures of working memory, was evaluated in three groups of postmenopausal women: (1) women who were tested when taking estrogen only (n = 38, M(age) = 55.1 years), (2) women who were tested when taking estrogen and a progestin concurrently (n = 23, M(age) = 55.9 years), and (3) women who were not taking hormone replacement therapy (n = 35, M(age) = 56.0 years). Estrogen users exhibited significantly better performance on a verbal task and on a spatial task, each with a prominent working memory component, but did not differ from nonusers on control tasks involving simple passive recall. These findings are consistent with the hypothesis that estrogen is active within PFC and is capable of influencing functions dependent on this region. The results of this study raise the possibility that estrogen may play a role in maintaining certain frontal lobe functions in women.     

Effect of postmenopausal hormone replacement therapy on lipoprotein and homocysteine levels in Chinese women.

Epidemiological studies have revealed that postmenopausal estrogen replacement therapy results in a marked reduction in the risk for cardiovascular diseases. In the present study, we evaluated plasma lipoprotein profile as well as homocysteine levels in 145 postmenopausal and premenopausal Chinese women living in Hong Kong. We also investigated the effect of hormone-replacement therapy (HRT) with estrogen or estrogen combined with progestin on plasma lipoprotein profile and homocysteine concentrations in those individuals. Postmenopausal women displayed significantly higher plasma levels of total cholesterol, LDL-cholesterol and apoB as well as higher plasma homocysteine levels than that of premenopausal women. HRT with either estrogen (17beta-estradiol or conjugated equine estrogen) alone or estrogen combined with progestin for 3.5-4.5 years significantly improved the lipoprotein profile in postmenopausal women by decreasing the levels of total cholesterol (12-20% reduction), LDL-cholesterol (26-29% reduction) and apoB (21-25% reduction). In women treated with 17beta-estradiol or conjugated equine estrogens their plasma levels of apoAl were significantly elevated (18% elevation) as compared to non-users. HRT also reduced plasma concentrations of homocysteine (13-15% reduction). In conclusion, we found that long-term HRT was associated with improvement in plasma lipoprotein profile and a reduction in homocysteine concentration in postmenopausal women. These results support the notion that the improvement of lipoprotein profile and a reduction in homocysteine concentration may contribute to the beneficial effect of HRT on cardiovascular risk.     

Effects of hormone replacement therapy on hemodynamic responses of postmenopausal women to passive heating

To examine theinfluence of chronic hormone replacement therapy (HRT) on the centraland peripheral cardiovascular responses of postmenopausal women todirect passive heating, seven women taking estrogen replacementtherapy, seven women taking estrogen and progesterone therapy, andseven women not taking HRT were passively heated with water-perfusedsuits to their individual limit of thermal tolerance.Measurements included heart rate (HR), cardiac output, blood pressure,skin blood flow, splanchnic blood flow, renal blood flow, esophagealtemperature, and mean skin temperature. Cardiac output was higher inwomen taking estrogen and progesterone therapy than in women not takingHRT (7.12 ± 0.70 vs. 5.02 ± 0.57 l/min at the limit ofthermal tolerance, respectively; P < 0.05) because ofa higher HR. However, when the HR data were plotted as a percentage ofthe maximum HR or percentage of HR reserve, there were no differencesamong the three groups of women. Neither splanchnic nor renal bloodflow differed among the groups of women. These data suggest that HRT has little effect on the cardiovascular responses to direct passive heating.

     

Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased?

OBJECTIVE--To quantify the effect of selection of relatively healthy women in studies reporting reduced relative risk for cardiovascular disease in postmenopausal women taking hormone replacement therapy. DESIGN--Review of the follow up studies reported in three recent meta-analyses to determine the effect of oestrogen therapy on both total cancer and cardiovascular disease. The same standard statistical methods as in the original analyses were used. MAIN OUTCOME MEASURES--Relative risks of total cancer and cardiovascular disease. RESULTS--In most of the follow up studies the relative risk for total cancer was below 1. The studies that showed the largest reduction in cardiovascular disease also showed the largest reduction in cancer, indicating a healthy cohort effect. Although heterogeneity within the studies prevented pooling, the best estimate for the protective effect on total cancer was a relative risk of 0.83 among women taking oestrogen (95% confidence interval 0.71 to 0.96), while in the same studies the relative risk for cardiovascular disease was 0.57 (0.50 to 0.64). CONCLUSIONS--Unintended selection of relatively healthy women for oestrogen therapy may have influenced the reported beneficial effect of oestrogen therapy on cardiovascular disease. It is unclear how much of the cardioprotection is due to this selection. Universal preventive hormonal replacement therapy for postmenopausal women is unwarranted at present.     

Serum leptin concentrations in response to acute exercise in postmenopausal women with and without hormone replacement therapy.

The purpose of the study was to examine the effects of acute exercise and hormone replacement therapy on serum leptin concentrations in postmenopausal women. Subjects were 15 healthy, postmenopausal women, 8 on hormone replacement therapy (HRT) and 7 not on hormone replacement therapy (NHRT). Group comparisons indicated no significant differences between HRT and NHRT groups with respect to age, height, weight, BMI, sum of skinfolds, or VO2max, and verified significant differences in estradiol and FSH concentrations. After an overnight fast, each subject completed 30 min of treadmill exercise at approximately 80% VO2max. Over 2 hr and 10 min, baseline, exercise, and recovery blood samples were collected from an intravenous catheter. A control session conducted a month later consisted of the same blood sampling protocol without exercise. Leptin concentrations declined significantly over the course of both the exercise and control sessions, gradually decreasing from baseline levels to -1.54 +/- 0.49 ng. ml-1 postexercise, and continuing to decline to a low of -2.89 +/- 0.59 ng. ml-1 at the end of the session. There was no significant difference between groups with respect to this decline. This is the first study to document that diurnal changes in leptin concentrations in postmenopausal women are not altered by acute treadmill exercise or HRT status. The study underscores the need to account for a diurnal reduction in leptin over the course of an exercise trial.     

Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy.

We tested the hypothesis that hormone replacement therapy (HRT)-related increases in C-reactive protein (CRP) would either be blunted or absent in postmenopausal women who regularly perform endurance exercise. Plasma CRP is an independent predictor of future cardiovascular events in healthy men and women. Oral HRT increases plasma CRP concentrations in postmenopausal women. Regular aerobic exercise reduces the risk of cardiovascular events and is associated with lower CRP concentrations in adults. To date, no study has evaluated the influence of habitual physical activity on the elevation of CRP associated with HRT. Plasma CRP concentrations were measured in 114 postmenopausal women: 39 physically active (endurance trained) and 75 sedentary postmenopausal subjects. Sixty-five women were users of HRT (22 physically active and 43 sedentary), and 49 were nonusers (17 physically active and 32 sedentary). CRP levels were approximately 75% higher (P < 0.01) in the sedentary users vs. nonusers of HRT (1.9 +/- 1.8 vs. 1.1 +/- 1.0 mg/l). In contrast, there was no difference in CRP levels between the physically active users and nonusers of HRT (0.6 +/- 0.4 vs. 0.4 +/- 0.2 mg/l; P = 0.61). Regardless of HRT status, CRP concentrations were approximately 65% lower in the physically active compared with sedentary women. In conclusion, physically active postmenopausal women exhibit lower plasma CRP concentrations compared with sedentary controls. Importantly, the HRT-related elevation in plasma CRP levels observed in sedentary women is absent in women who engage in regular endurance exercise. These data suggest that habitual physical activity may prevent the elevation in CRP concentrations due to HRT.     

Endocrine studies in postmenopausal women during oral replacement therapy with unconjugated oestrogens

Two groups of postmenopausal women were seen at monthly intervals during a three-month trial of continuous therapy with oral unconjugated oestrogens. Ten women in the first group were administered daily Hormonin No. 1 containing oestriol (E3) 0.135 mg, oestradiol (E2) 0.3 mg and oestrone (E1) 0.7 mg. Eight women in the second group received Hormonin No. 2 containing E3 0.27 mg, E2 0.6 mg and E1 1.4 mg. E1, E2, E3 and dehydroepiandrosterone (DHA) as well as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay. Maturation index of vaginal smears and clinical effects were also evaluated. Oral replacement therapy with these unconjugated oestrogens produced a significant elevation of E1 (p less than 0.05) and E2 (p less than 0.05) to values corresponding well with the premenopausal range measured in our laboratory. Postmenopausal levels of FSH and LH showed only a moderate but significant decrease (p less than 0.05). There was consistent relief of vasomotor symptoms. One case of endometrial focal adenomatous hyperplasia uncovered during the period of treatment was transformed to functional secretory endometrium after an appropriate course with progestogens. Oral administration of unconjugated oestrogens and periodic withdrawal bleeding induced with a progestational agent seems to be an effective method of replacement therapy in postmenopausal women.     

Effects of hormone replacement on growth hormone and prolactin exercise responses in postmenopausal women

Kraemer, R. R., L. G. Johnson, R. Haltom, G. R. Kraemer, H. Gaines, M. Drapcho, T. Gimple, and V. Daniel Castracane. Effects of hormone replacement on growth hormone and prolactin exercise responses in postmenopausal women. J. Appl.Physiol. 84(2): 703-708, 1998.Exercise elevatesgrowth hormone (GH) and prolactin (PRL) blood concentrations inpremenopausal women. Postmenopausal women taking hormone replacementtherapy (HRT) maintain higher estrogen levels that could affect GH andPRL. The purpose of the study was to determine the effects of HRT on GHand PRL responses to treadmill exercise. Seventeen healthy women whowere postmenopausal (naturally or surgically) [8 on HRT; 9 not onHRT (NHRT)], completed 30 min of treadmill exercise at 79.16 ± 1.2% maximal O₂ consumption (HRT group) and 80.19 ± 0.91% maximalO₂ consumption (NHRT group). Bloodsamples were collected from an intravenous catheter during an exercisesession and during a control session without exercise. GH and PRLconcentrations were significantly higher in the exercise trial than inthe nonexercise trial, whereas resting concentrations were similar forboth trials. GH and PRL peaked at 10.8 ± 1.60 and 12.67 ± 2.58 ng/ml, respectively, for HRT subjects and at 4.90 ± 1.18 and 9.04 ± 2.17 ng/ml, respectively, for NHRT subjects. GH concentrations inthe exercise trial were significantly higher for HRT than for NHRTsubjects. This is the first study to demonstrate that HRT enhancestreadmill-exercise-induced GH release and that similar PRL responses totreadmill exercise occur in postmenopausal women regardless of HRTstatus.

     

Relationship of physical fitness, hormone replacement therapy, and hemostatic risk factors in postmenopausal women.

This cross-sectional study evaluated the relationship of physical fitness, hormone replacement therapy (HRT), and hemostatic profiles at rest and after an acute bout of maximal exercise in 48 healthy postmenopausal women. Subjects were categorized by fitness and HRT user status into four groups: unfit nonusers, fit nonusers, unfit users, and fit users. Fibrinolytic variables tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and antigen and prothrombin fragment 1 + 2, a molecular marker of in vivo thrombin generation, were measured before and after maximal exercise. Fibrinogen was also measured at rest. Higher tPA and lower PAI-1 activities (P <0.05) were seen in HRT users and fit groups. tPA and PAI-1 antigens were lower in HRT and fit groups (P <0.05) but not after correction for body mass index. Prothrombin fragment 1 + 2 was lower in the fit groups regardless of HRT status (P <0.05). Fibrinogen was similar in all groups. Favorable hemostatic profiles were observed in physically fit compared with unfit women, especially in HRT nonusers. Thus fitness is more strongly related to these hemostatic risk factors compared with HRT since HRT did not affect these hemostatic variables in fit postmenopausal women.     

Cardiovascular, anthropometric and neurocognitive features of healthy postmenopausal women: effects of hormone replacement therapy

Randomized clinical trials have not shown long-term benefit of postmenopausal hormone replacement therapy (PHT) nor have they shown conclusively that the harmful consequences outweighs the benefits of the treatment. Rather, it is possible that an individualized hormone replacement therapy in questionably clinically healthy postmenopausal women may lead to different results than randomized trials. DESIGN: In this cross-sectional study we evaluated anthropometric parameters, body composition, serum lipids, blood pressure, heart rate variability (HRV) and neurocognitive functions in 39 healthy postmenopausal women PHT users or not users (n=13, age 53.0+/-3.3 and n=26, age=53.3+/-5.0 SD, respectively) as well as in 27 younger controls (ages=33.3+/-7.1). RESULTS: Demographic parameters were similar in women PHT users and not users. Postmenopausal women showed a significantly increase of body mass index (BMI) as well as of waist circumference, compared to younger controls, but in PHT users the values of fat free mass were intermediate between the ones of not treated and younger women. The study of HRV showed a reduction in low frequency (LF) component (sympathetic modulation) during the day, and a reduction in high frequency (HF) component (parasympathetic modulation), particularly in postmenopausal women without PHT. PHT users were characterized by autonomic parameters intermediate between younger controls and age-matched women without PHT. CONCLUSIONS: The impact of PHT on the age-dependent changes of anthropometric features and body composition seems to be modest but positive. Furthermore, PHT seems to play a positive role on the autonomic modulation of cardiac function, through a shift of LF/HF ratio values towards those of young controls.     

Hormone replacement therapy increases renal kallikrein excretion in healthy postmenopausal women

Hypertension and its related increase in cardiovascular morbidity in postmenopausal women is a major public health problem. The hypotensive property of urinary kallikrein has been described since 1909. Despite the controversy surrounding the effects of hormone replacement therapy on blood pressure regulation, its mechanisms remain incompletely understood, and no evidence has yet been provided for its effects on renal kallikrein excretion in postmenopausal women. In a double-blind, randomized study we examined the effects of hormone replacement therapy in the form of 2 mg 17-beta estradiol (ERT) or 2 mg 17-beta estradiol combined with continuous 5 mg medroxyprogesterone acetate (HRT) on urinary kallikrein excretion in postmenopausal women. Thirty-nine postmenopausal women collected their urine for 24 hours on two separate occasions 3 months apart. During the 3 month period women were randomized to placebo, ERT, or HRT. Urine samples were assayed for kallikrein activity, normalized to urine creatinine and expressed as mU/gm creatinine. Urinary kallikrein excretion increased significantly after 3 months in the ERT (p < 0.001) and HRT (p < 0.01) groups, and decreased non-significantly in the placebo group (p > 0.06). There were no significant blood pressure changes after 3 months of therapy. The findings demonstrate that hormone replacement therapy in the form of estrogen or estrogen combined with continuous medroxyprogesterone is effective in increasing urinary kallikrein excretion. Given that a decrease in kallikrein excretion may mark risk for development of hypertension, the findings of this study are of value in demonstrating a novel mechanism underlying cardioprotective properties of postmenopausal hormone replacement therapy in women without pre-existing coronary disease.     

Serum estradiol concentration as measured by HPLC-RIA and bone mineral density in postmenopausal women during hormone replacement therapy

OBJECTIVE: To determine the relationship between the serum estradiol concentration and bone mineral density (BMD) of the lumbar spine in postmenopausal women treated with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) every other day and every day. METHODS: Eighty-four postmenopausal women were randomly treated with hormone replacement therapy (HRT) every other day and every day. Forty-seven women received oral administration of 0.625 mg CEE and 2.5 mg MPA every other day, and 37 women received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. BMD of the lumbar spine at 12 months and serum concentrations of estradiol and estrone at 6 and 12 months after treatment were examined. RESULTS: The estradiol concentration in subjects treated every other day showed a significant (p < 0.001) positive correlation with the percentage change in lumbar BMD, while that in subjects treated every day was not correlated with the percentage change in BMD. The differences between serum estradiol concentrations after 12 months of treatment and initial serum estradiol values in women treated every other day and every day also showed a significant (p < 0.01 and 0.05, respectively) positive correlation with percentage changes in BMD. In women treated every other day, body mass index (BMI) in the subjects in whom BMD did not increase was significantly (p < 0.01) lower than that in the subjects in whom BMD did increase. CONCLUSIONS: The serum estradiol concentration in women treated every other day has a strong positive correlation with the percentage change in lumbar BMD, but a higher estradiol concentration may be needed for women in whom BMD did not increase with HRT every other day after due consideration of individual characteristics such as BMI.     

Effect of hormone replacement therapy on the production of bone-resorbing cytokines by peripheral blood cells in postmenopausal women.

We studied the effects of hormone replacement therapy (HRT) with estrogen on postmenopausal changes in the production of bone-resorbing cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta were significantly higher in women in their 40s and 50s and in postmenopausal women than in women in their teens, 20s and 30s, while the levels of TNFalpha did not show any changes related to age. Both levels in HRT-treated women were significantly lower than those in untreated women at almost every postmenopausal stage. In a prospective study, HRT induced significant declines in both levels. These results show that estrogen decreases the accelerated production of IL-1beta and reduces the production of TNFalpha in postmenopausal women at each postmenopausal stage, even in late-postmenopausal women.     

Utilisation of hormone replacement therapy by women doctors.

OBJECTIVES--To ascertain the prevalence and duration of use of hormone replacement therapy by menopausal women doctors. DESIGN--Postal questionnaire. SETTING--General practices in the United Kingdom. SUBJECTS--Randomised stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current principal list of the Medical Register. MAIN OUTCOME MEASURES--Prevalence and duration of use of hormone replacement therapy; menopausal status. RESULTS--Overall, 45.7% (436/954) of women doctors aged between 45 and 65 years had ever used hormone replacement therapy. When the results from women still menstruating regularly were excluded, 55.2% (428) were ever users and 41.2% (319) current users. The cumulative probability of remaining on hormone replacement therapy was 0.707 at five years and 0.576 at 10 years. CONCLUSIONS--Women doctors have a higher prevalence of use of hormone replacement therapy than has been reported for other women in the United Kingdom, and most users seem to be taking hormone replacement therapy for more than five years. The results may become generalisable to the wider population as information on the potential benefits of hormone replacement therapy is disseminated.