Metabolic changes induced by peroral oestrogen and transdermal oestradiol gel therapy

Objective To investigate changes in plasma lipid and lipoprotein levels induced by peroral oestrogen replacement and transdermal oestradiol gel therapy.
Design The effects of peroral oestradiol valerate tablets (2 mg) and placebo gel were compared with 1g transdermal oestradiol gel (1mg oestradiol) and placebo tablets in a randomised, double-blind, double-dummy study for 6 months.
Setting Department of Internal Medicine, University of Oulu and Oulu Deaconess Institute, Oulu, Finland.
Population Seventy-nine hysterectomised, postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group.
Main outcome measures Cholesterol and triglycerides in total plasma and in various lipoprotein fractions, and sex hormones.
Results In the peroral oestrogen group total and LDL cholesterol were decreased and HDL cholesterol and triglycerides were increased. In the oestradiol gel group plasma total, LDL and VLDL cholesterol and the ratio of LDL/HDL cholesterol were significantly decreased, but no change in HDL cholesterol and triglycerides was observed. Overall the decrease in LDL levels was correlated with the increase in oestrogen levels.
Conclusions Both peroral and transdermal replacement therapy had beneficial effects on plasma lipids by lowering total and LDL cholesterol and LDL/HDL cholesterol ratio. These changes seem to be associated with changes in oestrogen levels.     

Piperazine oestrone sulphate and interrupted norethisterone in postmenopausal women: effects on bone mass, lipoprotein metabolism, climacteric symptoms, and adverse effects

Objective To compare the effects of two doses of piperazine oestrone sulphate combined with interrupted norethisterone, with that of oestradiol continuously combined with norethisterone acetate, and with placebo, in postmenopausal women.
Design A prospective randomised trial.
Participants Two hundred postmenopausal women.
Setting Monocentre study with expertise in osteoporosis.
Methods The participants were randomly assigned to two years of treatment with alternating three-day cycles of 1.5 mg of piperazine oestrone sulphate plus 0.7 mg of norethisterone (highEP), or alternating three-day cycles of 0.75 mg of piperaine oestrone sulphate plus 0.35 mg of norethisterone (lowEP), or 2 mg of 17β-oestradiol continuously combined with 1 mg of norethisterone acetate (E₂+NETA), or placebo.
Main outcome measures Change in bone mineral density, lipoprotein metabolism, climacteric symptoms, and adverse effects.
Results One hundred and twenty-one women completed the study. Spinal bone mineral density was increased about 9% over two years by E₂+NETA, about 6% by highEP, 4% by lowEP, but remained unchanged in the placebo group. The same pattern was seen in the hip and forearm. All hormone regimens decreased markers of bone turnover and alleviated climacteric symptoms. Serum lipoproteins decreased by about 10% in all hormone groups.
Conclusions All hormone regimens studied prevented bone loss completely and lowered serum lipids.     

Effects of estrone sulfate alone or with medroxyprogesterone acetate on serum lipoprotein levels in postmenopausal women

OBJECTIVE: To determine the effects of estrone sulfate alone or with different doses of medroxyprogesterone acetate on serum lipid and lipoprotein levels. METHODS: A multicenter, double-masked, randomized trial for 1 year involved 682 postmenopausal women, aged 53.8 +/- 0.2 years (mean +/- standard deviation) with intact uteri. Subjects received fixed daily doses of 0.625 mg of estrone sulfate and one of the following regimens: placebo; 2.5 mg daily of medroxyprogesterone acetate; 5 mg daily of medroxyprogesterone acetate; or 10 mg of medroxyprogesterone acetate for the first 12 days of each 28-day cycle. Fasting lipid and lipoprotein levels were measured at baseline and weeks 12, 16, 24, 30, 36, and 52 of treatment. Absolute mean changes from baseline were determined by paired t test, and treatment effects were determined by analysis of variance. RESULTS: Total cholesterol levels decreased significantly (P <.05) from baseline in all study groups; however, reduction was significantly greater (P <.001) in the 2.5-, 5-, and 10-mg groups (-13.3%, -15.2%, and -14.1%) than in the placebo group (-4.9%). Low-density lipoprotein cholesterol levels decreased significantly and equally in all groups (-10.1% to -12.3%). High-density lipoprotein cholesterol levels increased by 3.2% with unopposed estrogen (P <.05) and did not change from baseline with combined therapy. Triglyceride and very low-density lipoprotein cholesterol levels increased by 13.4% and 2.7%, respectively, in the placebo group, did not change in the 2.5-mg group, decreased by 10.2% and 2.0% and by 11.4% and 2.2% in the 5- and 10-mg groups, respectively (P <.05). CONCLUSION: Estrone sulfate at the daily dose of 0.625 mg alone or with medroxyprogesterone acetate significantly improved lipoprotein levels. Combined therapy with medroxyprogesterone acetate and estrone sulfate was associated with statistically significantly greater reduction in total cholesterol and statistically significantly less increase in triglyceride levels than unopposed estrone sulfate therapy.     

Continuous Combined Piperazine Oestrone Sulphate and Medroxyprogesterone Acetate Hormone Replacement Therapy - A Study of Bleeding Pattern, Endometrial Response, Serum Lipid and Bone Density Changes

Summary: This pilot study was conducted to establish the optimum oral dosage of medroxyprogesterone acetate (Provera) given daily in combination with a fixed dose of piperazine oestrone sulphate (Ogen), as hormone replacement therapy. A group of 32 nonhysterectomized, symptomatic menopausal women were randomly allocated to receive piperazine oestrone sulphate 1.25 mg daily and medroxyprogesterone acetate 2.5 mg, 5 mg or 10 mg daily for a 2-year period. This was an open study and the patients were reviewed at 3-monthIy intervals for 2 years. Vaginal bleeding was reported by 58% of patients after the first 3 months of treatment. There was a gradual decline in the reported incidence of bleeding over the following 6 months particularly by women in the 5 mg and 10 mg Provera group. Only 10% of patients were still recording slight bleeding in the 10 mg group at 12 months. By 24 months all the women in the 5 mg and 10 mg Provera groups had ceased bleeding. There were 2 patients in the 2.5 mg Provera group with persistent proliferative endometrium at 24 months. All the remaining patients had atrophic endometrium. There was no significant difference in serum lipid changes between the 3 groups, but there was an overall reduction in total cholesterol, triglycerides and low density lipoprotein cholesterol in all women. There was no significant difference in bone mineral density changes between the groups over the 2-year period. Endometrial protection with increased incidence of amenorrhoea, without significant adverse effects, was seen with the use of 5 mg and 10 mg of provera.     

Overview of the relationship between use of progestogen-only contraceptives and bone mineral density

Objectives To summarise the available epidemiological evidence regarding the relationship between the use of progestogen-only contraceptives and bone mineral density.
Design and methods Overview of the published epidemiological literature.
Results Overall, 17 studies of the use of progestogen-only contraceptives and bone mineral density were identified, involving 1529 women exposed to progestogen-only contraceptives and 2086 controls. Sixty-eight percent of the data relate to the effects of use of depot medroxyprogesterone acetate. Average bone mineral density was reduced in current users of depot medroxyprogesterone acetate compared with non-users, although density in users was within one standard deviation of the mean in non-users. There was significant heterogeneity between the results of different studies (   P <0.0001  ). The reduction in bone mineral density appeared to be greater at the lumbar spine, femoral neck and ultradistal forearm than at the midshaft of the ulna. Studies involving women with a longer average duration of use of depot medroxyprogesterone acetate displayed greater reductions in bone mineral density compared with studies of women with shorter durations of use. Based on limited data, no difference in bone mineral density was observed between former and never users of depot medroxyprogesterone acetate. Results regarding the effect of levonorgestrel implants were conflicting. Studies of progestogen-only oral contraceptives and the progesterone vaginal ring were small and restricted to lactating women.
Conclusions Women currently using depot medroxyprogesterone acetate have a lower average bone mineral density than non-users. The magnitude of this effect is uncertain but appears to be greater with longer durations of use.     

Transdermal oestradiol gel in the treatment of the climacterium: a comparison with oral therapy

Objective To compare two doses of a transdermal oestradiol gel (Divigel®/Sandrena®) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina®/Dilena®).
Design Two-year, randomised, open-label, comparative study.
Setting Menopausal outpatient clinic in Helsinki.
Subjects Postmenopausal women with climacteric complaints or already using HRT.
Interventions (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last 10 days. In all groups, each treatment period was followed by a 7-day medication-free interval.
Main outcome measures Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety.
Results With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourable changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation.
Conclusions Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient, well-tolerated form of HRT.     

Lipid changes after hormone replacement therapy for menopause

Three regimens of hormone replacement therapy were administered to 62 postmenopausal women for a period of 12 weeks and evaluated for their effect on blood lipids. Each group was given a continuous dose of 0.625 mg of conjugated estrogens combined with either a continuous dose of 2.5 mg of medroxyprogesterone acetate or 5.0 mg of medroxyprogesterone acetate, or a cyclic dose of 5.0 mg of medroxyprogesterone acetate on days 17-28 of the cycle. After treatment there was a significant decrease in the total cholesterol (P less than .0007) and low density lipoprotein cholesterol (P less than .0001) together with a significant increase in high density lipoprotein cholesterol (P less than .0029). There was no significant difference in the response of the blood lipids to the three hormone groups. Therefore, preference would depend on the combination that caused the least bleeding or amenorrhea.     

Serum lipids and lipoproteins in continuous or cyclic medroxyprogesterone acetate treatment in postmenopausal women treated with conjugated estrogens

This study evaluates effects on serum lipids of continuous or sequential progestogens for hormonal replacement in women. Subjects received either a cyclic regimen of replacement (0.625 mg/d of conjugated equine estrogens (Es) for 25 days/month and 10 mg medroxyprogesterone acetate [MPA] for the last 13 days of E) or 0.625 mg/d E along with either 5 or 10 mg MPA (Provera, Upjohn Company, Kalamazoo, MI). Study parameters were measured over a 24-week period. No differences in total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins I and II, sex hormone-binding globulin, or serum MPA levels were noted between the sequential and 5 mg continuous group. The 10 mg MPA group did not have an increase in HDL or decrease in low-density lipoprotein as did the other groups.     

The influence of medroxyprogesterone acetate on the effects of transdermal oestradiol replacement therapy on plasma lipids.

A prospective study was carried out on 82 healthy menopausal women to determine whether or not there is an attenuation of the cardioprotective effects of continuous transdermal oestradiol on plasma lipid and lipoprotein concentrations with the use of sequential oral medroxyprogesterone acetate. Group 1 comprised 51 hysterectomised women on transdermal oestradiol (50 microg daily). Group 2 included 31 women with an intact uterus on oestradiol (50 microg daily) and medroxyprogesterone acetate (10 mg daily for the first 12 days of each calendar month). Women maintained on 50 microg throughout 6 months (group 1: n = 29; group 2: n = 20) were reviewed for changes in plasma lipids and lipoproteins at the end of 6 months (group 1), and in the combined phase of treatment in the seventh month (group 2). In group 1, there was a reduction in the concentrations of total cholesterol (- 6.3%, P = 0.004) and LDL-cholesterol (- 6.1%, P = 0.05). In group 2, there were no significant changes in total cholesterol (- 4.8%, P = 0.23) and LDL-cholesterol (- 5.8%, P = 0.30). HDL-cholesterol levels did not change significantly with unopposed oestradiol (+ 3.8%, P = 0.30), or with additional medroxyprogesterone acetate (0%, P = 0.94). Serum triglyceride concentrations decreased significantly in both the groups (- 14.3%, P = 0.001, and- 12.8%, P = 0.006, respectively). There were no statistically significant differences in the changes in the respective plasma lipid parameters on comparing the two treatment groups (P > 0.4 for all comparisons, Student's t -tests). The plasma lipid and lipoprotein profile encountered at the end of 6 months, was also generally maintained in 24 women (group 1: n = 13; group 2: n = 11) who completed 1 year of the study. Transdermal oestradiol may be of particular clinical benefit for women with hypertriglyceridaemia. Medroxyprogesterone acetate did not exert a significantly adverse influence on plasma lipid and lipoprotein concentrations.     

Bone density in long term users of depot medroxyprogesterone acetate

Objective To identify any adverse effect on bone density in long term users of depot medroxyprogesterone acetate (DMPA) for contraception.
Design Cross-sectional measurement of bone density in users with amenorrhoea of more than one year or any woman using DMPA for more than five years.
Setting Community Family Planning Clinics in Portsmouth and Manchester.
Population One hundred and eighty-five women aged 17–52 years (mean 33.3 years) who had used DMPA for between 1 and 16 years and were attending the clinics for further injections, between August 1994 and August 1996.
Methods Dual energy X-ray measurement of bone density of femoral neck and lumbar spine, and venous blood sample taken just prior to the next injection of DMPA.
Main outcome measures Bone density of femoral neck and lumbar spine and serum oestradiol in relationship to years of DMPA use and duration of amenorrhoea.
Results Most women (   n = 153  ) had serum oestradiol levels < 150 pmol/l. Despite this, the mean bone density of the lumbar spine compared with the population mean for women aged 20–59 years gave a Z score (95% CI) of -0.332 (-0.510 to -0.154). There was no significant difference in the mean density of the femoral neck from the normal population mean.
Conclusion Despite amenorrhoea and low serum oestradiol, this sample of long term DMPA users had bone density only minimally below the normal population mean. We therefore found no clinically important adverse effect on bone density and therefore no reason to recommend bone conserving measures, such as add-back oestrogen.     

The effects of progestins on bone density and bone metabolism in postmenopausal women: a randomized controlled trial

OBJECTIVE: The purpose of this study was to evaluate the action of progestins on bone metabolism in early menopausal women. STUDY DESIGN: One hundred thirty-two menopausal women were randomized into a 2-year double-blinded, placebo-controlled clinical trial. There were 6 treatment groups: micronized progesterone (P 4 ) 300 mg/day; medroxyprogesterone acetate (MPA) 10 mg/day; norethindrone (NET) 1 mg/day; micronized estradiol (E 2 ) 1 mg/day; E 2 1 mg/day + MPA 10 mg/day; and placebo. All subjects received 1000 mg of calcium and 400 IU of vitamin D/day. Primary outcome variables were bone mineral density (BMD) changes at the spine and hip. Secondary variables were bone turnover markers. RESULTS: With E 2 or E 2 +MPA treatment, BMD at L2-L4 increased by 2% to 4% over 2 years. Bone mineral density (BMD) at the spine followed a decreasing trend with MPA, P 4 , and placebo treatments. With NET treatment, BMD did not change from baseline. At the femoral neck site, BMD did not change significantly for any treatment group. Bone resorption and bone formation markers decreased with E 2 or E 2 +MPA treatment, and did not change appreciably with all 3 progestin-alone treatments. There were no vertebral or hip fractures observed during the trial. CONCLUSION: Estrogen remains the primary bone active agent in hormone therapy, while progestins have significantly less activity. The selection of the appropriate progestin in hormone therapy should be based on criteria other than bone activity.     

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception

OBJECTIVE: The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception. STUDY DESIGN: One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment. RESULTS: Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus -1.8% in the placebo group ( P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus -5.1% in the placebo group ( P <.001). CONCLUSION: Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.     

Long term effects of oestrogen therapy on bone loss in postmenopausal women: a 23 year prospective study

Objective   To determine the long term effect of oestrogen therapy on bone loss after menopause.
Design   Prospective observational study over 23 years.
Setting   Malmö, Sweden.
Subjects   Twenty-eight women taking oestrogen and 196 women not taking oestrogen during the follow up.
Methods   Bone mineral density of the forearm was measured by single-photon absorptiometry at age 48 and 72 years. Use of oestrogen therapy was noted.
Main outcome measure   Rate of forearm bone loss between the age of 48 and 72 years.
Results   Women taking oestrogen, for a median of 17 years (range 4 to 26), had 8.7 percentage points (95% CI 3.8–13.5) lower rate of bone loss compared with women not taking oestrogen during the same period. Each year of oestrogen therapy reduced the rate of bone loss by 0.8 percentage points (95% CI 0.2–1.4).
Conclusions   The use of oestrogen seems to reduce the rate of bone loss over a period of 23 years, and the longer the duration of the therapy, the less bone loss.     

Increased susceptibility to low density lipoprotein oxidation in women with a history of pre-eclampsia

Objectives To evaluate the susceptibility to oxidation of low density lipoprotein (LDL) in women with a history of pre-eclampsia.
Design A case–control study.
Setting The departments of obstetrics and gynaecology at two university teaching hospitals.
Population Women delivering one to three years before enrolment, 35 who were diagnosed with severe pre-eclampsia and 35 controls matched for age, body mass index (BMI), smoking and parity.
Methods Plasma samples were analysed for total cholesterol, high density lipoprotein (HDL) cholesterol, LDL cholesterol, triglycerides and lipoprotein A. The in vitro susceptibility to oxidation of LDL was measured and expressed in minutes (lag time). Results are expressed as mean and standard deviation.
Main outcome measures Serum lipid profile and in vitro susceptibility to oxidation of LDL.
Results Mean LDL cholesterol (116 [37] vs 98 [20] mg/dL, P < 0.05) and trygliceride (112 [56] vs 78 [38] mg/dL, P < 0.05) levels were significantly higher in the groups of women who had pre-eclampsia compared with controls. The rest of the measured lipid parameters were similar between the two study groups. The susceptibility to oxidation of LDL was also significantly higher in the pre-eclampsia group (lag time: 37.9 [8.4] vs 44.8 [9.1] minutes, P < 0.01).
Conclusion Women with a history of pre-eclampsia have significant differences in lipid parameters and an increased susceptibility to lipoprotein oxidation when compared with women who had a normal pregnancy one to three years after delivery.     

Prevention of osteoporosis by medroxyprogesterone acetate in postmenopausal women.

The effect of medroxyprogesterone acetate 10 mg BID alone, conjugated estrogens alone or in a combination regimen for the prevention of osteoporosis was determined in 36 postmenopausal women using single photon densitometry. No significant differences in cortical or trabecular bone mass over time were detected in women between the three treatment groups, although a slight increase in bone mass was noted in women with the combined therapy. Medroxyprogesterone acetate appears efficacious in preventing postmenopausal osteoporosis, and may be especially useful in women with contraindications to estrogen replacement therapy.     

Comparison of continuous versus sequential estrogen and progestin therapy in postmenopausal women.

A pilot study was performed comparing the efficacy and safety of continuous versus sequential schedules of the two most commonly prescribed medications for ovarian hormone replacement, conjugated equine estrogens and medroxyprogesterone acetate. Bleeding patterns, endometrial histology, and metabolic parameters were studied in 48 postmenopausal women prospectively randomized to a continuous schedule (daily estrogen and progestin) or a sequential schedule (conjugated estrogen on days 1-25, medroxyprogesterone acetate on days 16-25). Doses studied were 0.625 and 1.25 mg of conjugated estrogens and 10 mg of medroxyprogesterone acetate. Significantly greater bleeding was observed with the 1.25-mg dosage of conjugated estrogens. Bleeding patterns were similar between schedules, with the exception that amenorrhea was more prevalent in the women using the 1.25-mg dosage of estrogen and the continuous progestin schedule. More frequent endometrial atrophy was observed with the continuous schedule, supporting the concept that prolonged use of this schedule may promote amenorrhea in most patients. Both doses and schedules were associated with modest and insignificant increases in high-density lipoprotein cholesterol. Sequential therapy did not prevent the estrogen-induced decrease of low-density lipoprotein cholesterol, whereas the continuous schedule did, particularly with 0.625-mg dosage of conjugated estrogens. Significant increases of triglycerides were also seen with the continuous but not with the sequential schedule. Because of reports that the continuous schedule using the 2.5-mg dosage of medroxyprogesterone acetate does not elicit these actions on circulating lipids, attention should be directed toward examining the long-term effects of this lower dosage given continuously.     

Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women

Serum lipids and lipoproteins were examined in a group of 45 healthy postmenopausal women who were treated for 2 years with either 3 mg of percutaneous estradiol (n = 20) or placebo (n = 25). Percutaneous estradiol was given alone during the first year of treatment and in combination with oral micronized progesterone (200 mg) for 12 days of each cycle during the second year. The women were examined every 3 months throughout the 2 years. Percutaneous estrogen therapy significantly reduced total serum cholesterol and low-density lipoprotein cholesterol, whereas no significant differences were observed in serum triglycerides and high-density lipoprotein cholesterol. Addition of oral progesterone during the second year of treatment did not produce any significant alterations in serum total cholesterol or low-density lipoprotein cholesterol, both of which remained significantly reduced. Serum triglycerides remained virtually unchanged, whereas a slight but significant increase (p less than 0.05) was observed in high-density lipoprotein cholesterol levels at the end of the study period. We conclude that percutaneous estrogen administration produces changes in total serum cholesterol and low-density lipoprotein cholesterol levels similar to those observed after oral estrogen administration. However, the magnitude and time course of the response seem to be modulated by the route of administration. Addition of oral micronized progesterone does not influence the beneficial estrogenic actions on serum lipids and lipoproteins and seems to be a proper "progestogen" in percutaneous estrogen therapy.     

A randomized, double-blind, placebo-controlled, cross-over trial to assess the side effects of medroxyprogesterone acetate in hormone replacement therapy.

Cyclic progestin therapy has been widely advocated as an adjunct to postmenopausal estrogen replacement therapy to reduce the risk of endometrial carcinoma. Acceptance of this approach, however, appears to have preceded detailed evaluation of possible adverse side effects of progestins that could result in patient noncompliance. We evaluated the nonmenstrual physical and psychological side effects of oral medroxyprogesterone acetate given in conjunction with transdermal estrogen in two groups of women with previous hysterectomy and oophorectomy. Twenty-four women with prospectively documented severe premenstrual syndrome (PMS) before surgery and 24 women with no such history of adverse premenstrual changes received transdermal estrogen 100 micrograms on days 1-25 and either oral medroxyprogesterone acetate 10 mg daily or an identical placebo (days 12-25) in a randomized, double-blind, cross-over design. Mood and physical symptoms were monitored prospectively, using daily self-ratings on the Daily Symptoms Checklist. The Beck Depression Inventory and Premenstrual Tension Self-Rating Scale were completed on day 24. At the study's completion, the patients were asked which treatment period they preferred. Paired comparisons did not reveal any significant differences, and preference for treatment was equally divided between medroxyprogesterone acetate and placebo. We conclude that addition of medroxyprogesterone acetate 10 mg/day for 14 days to cyclic transdermal estrogen therapy (days 1-25) produces no consistent adverse physical or psychological effects on women for one cycle of treatment, regardless of their PMS history.     

Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception

OBJECTIVE: The purpose of this study was to determine the rate of early postmenopausal bone loss in women who had used depot medroxyprogesterone acetate contraception through to menopause. STUDY DESIGN: Bone mineral density at the lumbar spine and femoral neck was assessed prospectively over 3 years in 15 women who reached a natural menopause and who did not undergo hormone replacement therapy and in 16 long-term users of depot medroxyprogesterone acetate who discontinued depot medroxyprogesterone acetate only on reaching menopause. Of the latter, 5 women subsequently underwent hormone replacement therapy. RESULTS: Early menopausal bone loss was rapid in the control group (6% from both sites over 3 years), but the users of depot medroxyprogesterone acetate (who did not take hormone replacement therapy) showed little change in bone mineral density. Between-group differences were statistically significant at years 2 and 3 at both sites (P <.03-<.002). In the users of depot medroxyprogesterone acetate who underwent hormone replacement therapy, bone mineral density increased significantly (P <.03) at the lumbar spine and was stable at the femoral neck. CONCLUSION: Women who use depot medroxyprogesterone acetate through to menopause have attenuated rates of bone loss from the lumbar spine and femoral neck, presumably because they have already lost the estrogen-sensitive component of bone.