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Elevated serum levels of endometrial secretory protein PP14 in patients with advanced endometriosis. Suppression by treatment with danazol and high-dose medroxyprogesterone acetate.

The circulating concentration of endometrial protein PP14 varied during the menstrual cycle in patients with endometriosis. The highest levels were found on days 1 to 4 of the cycle (176 +/- 123 micrograms/L; mean +/- SD), and the lowest on days 5 to 20 (44.1 +/- 29.7 micrograms/L). Rising levels were observed on days 21 to 30 (58.3 +/- 62.6 micrograms/L). On days 5 to 20 (i.e., during period of the lowest levels) patients with advanced endometriosis had higher PP14 levels (63.9 +/- 39.0 micrograms/L) than those with mild endometriosis (29.3 +/- 18.2 micrograms/L; p less than 0.01). Patients with mild endometriosis had slightly higher serum PP14 levels than apparently healthy control subjects (p less than 0.05), but overlapping of values between the two groups is remarkable. Conservative surgical elimination of endometriosis significantly decreased the serum PP14 levels. Treatment with danazol (600 mg/day), or with medroxyprogesterone acetate (100 mg/day) after laparoscopy also resulted in significant decreases in the serum PP14 concentration. After 6 months of treatment, conservative surgery in combination with danazol or with medroxyprogesterone acetate, yielded more pronounced declines in serum PP14 level than conservative surgery plus placebo. No significant difference was observed between the effects of danazol and medroxyprogesterone acetate. We conclude that endometriosis tissue contributes to the circulating PP14 level, and the decline in PP14 level during danazol and medroxyprogesterone acetate treatments reflects regression of intrauterine and ectopic endometrial tissues.

Adult↗

Culture characteristics of human endometrial glandular epithelium throughout the menstrual cycle: modulation of deoxyribonucleic acid synthesis by 17 beta-estradiol and medroxyprogesterone acetate.

OBJECTIVE: The purpose of this study was to evaluate the culture characteristics and cell proliferation of human endometrial glandular epithelial cells in primary culture on extracellular matrix and to evaluate sex steroid modulation of this process. STUDY DESIGN: We examined the culture characteristics in 53 endometrial gland preparations obtained throughout the menstrual cycle and determined the incorporation of tritiated thymidine in endometrial epithelial cells as a measure of deoxyribonucleic acid synthesis (cell proliferation) in the presence and absence of 17 beta-estradiol and medroxyprogesterone acetate. RESULTS: Good culture maintenance of endometrial epithelial monolayers on extracellular matrix was observed from glands derived from proliferate phase endometrium (21 of 23), whereas poor adherence and culture maintenance was observed in all 30 of specimens from the secretory phase. With 17 beta-estradiol treatment for 22 hours, tritiated thymidine incorporation was not different from control, but medroxyprogesterone acetate treatment for 22 hours was associated with diminished tritiated thymidine incorporation by 36% (p < 0.004). When 17 beta-estradiol (10(-8) mol/L) was included in the incubation medium from the time of initial culture, tritiated thymidine incorporation on day 4 was 40% of control (p < 0.006), and tritiated thymidine was not suppressed further by 22 hours of treatment with medroxyprogesterone acetate (10(-7) mol/L). In spite of cellular spread of endometrial epithelial cells to subconfluence, deoxyribonucleic acid content per well did not increase over time in culture. CONCLUSIONS: We conclude that exposure of endometrial glands to progesterone in vivo inhibits adherence and the establishment of cell monolayers cultured on a thin layer of extracellular matrix. Because 17 beta-estradiol treatment in culture for 22 hours does not increase tritiated thymidine incorporation, it is possible that 17 beta-estradiol exerts its proliferative effect on the endometrial epithelium by an indirect action mediated by stromal cells. The effects of 17 beta-estradiol and medroxyprogesterone acetate on deoxyribonucleic acid synthesis in endometrial epithelial cells may represent an action on a stem cell population of dividing cells or a terminally differentiated cell population that undergoes programmed cell death.

Cells, Cultured↗

Use of menopausal estrogens and medroxyprogesterone in the United States, 1982-1992.

OBJECTIVE: To describe trends in the prescription of menopausal estrogens and medroxyprogesterone in the United States. METHODS: Annual estimates of the number of prescriptions for menopausal estrogens and medroxyprogesterone and descriptive information on patients and providers were obtained from two pharmaceutical marketing research data bases, the National Prescription Audit and the National Disease and Therapeutic Index of IMS America. RESULTS: An estimated 13.6 million prescriptions were dispensed for oral menopausal estrogens in 1982, and 31.7 million in 1992, a 2.3-fold increase (P = .0001). In 1992, Premarin, the only oral conjugated estrogen currently approved for use, was the most frequently dispensed brand-name pharmaceutical in the United States. Dispensed prescriptions for Estraderm, a transdermal estradiol first marketed in 1986, increased from 1.5 million in 1987 to 4.7 million in 1992. Dispensed prescriptions for oral medroxyprogesterone also increased from 2.3 million prescriptions in 1982 to 11.3 million in 1992, a 4.9-fold increase (P = .0001). An estimated one in six to one in four postmenopausal women were taking menopausal hormones in 1992. These drugs were prescribed mainly by obstetrician-gynecologists. CONCLUSION: The use of menopausal estrogens and medroxyprogesterone has increased substantially over the past decade. These trends indicate that American women are widely exposed to menopausal hormone replacement.

Administration, Cutaneous↗

Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group.

OBJECTIVE: We evaluated four oral combinations of conjugated estrogens (Premarin) and medroxyprogesterone acetate in preventing endometrial hyperplasia, which can occur with conjugated estrogens alone. STUDY DESIGN: This was a 1-year prospective, double-blind, randomized, multicenter study in 1724 postmenopausal women. All five groups took conjugated estrogens (0.625 mg) daily. The respective medroxyprogesterone acetate dosages were 2.5 and 5.0 mg daily (groups A and B) and 5.0 and 10.0 mg for 14 days per 28-day cycle (groups C and D). RESULTS: Among the 1385 patients with valid biopsy data, endometrial hyperplasia developed in 20% in the conjugated estrogens-treated group and < or = 1% in each of the four conjugated estrogens/medroxyprogesterone acetate-treated groups. The incidence of endometrial hyperplasia did not differ significantly between any of the conjugated estrogens/medroxyprogesterone acetate regimens. However, none of the patients receiving the two higher medroxyprogesterone acetate dosages (groups B and D) had endometrial hyperplasia. CONCLUSION: The endometrial hyperplasia incidence was significantly lower in women treated with conjugated estrogens and medroxyprogesterone acetate than in women treated with conjugated estrogens alone.

Aged↗

Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm.

Cardiovascular disease, the major cause of death in post-menopausal women, can be reduced by replacement of ovarian steroid hormones. To compare medroxyprogesterone with progesterone as the progestin in hormone replacement therapy from the standpoint of coronary artery vasospasm, we treated ovariectomized rhesus monkeys with physiological levels of estradiol-17 beta in combination with medroxyprogesterone or progesterone for four weeks. Coronary vasospasm in response to pathophysiological stimulation without injury showed that progesterone plus estradiol protected but medroxyprogesterone plus estradiol failed to protect, allowing vasospasm. We conclude that medroxyprogesterone in contrast to progesterone increases the risk of coronary vasospasm.

Animals↗

The influence of transdermal oestradiol replacement therapy and medroxyprogesterone acetate on serum lipids and lipoproteins.

AIMS: The objective of this study was to examine the effects of continuous transdermal oestradiol with or without sequential oral medroxyprogesterone acetate on serum lipids and lipoproteins in menopausal women. METHODS: Sixty-two healthy menopausal women, attending at two menopause clinics in Western India, were recruited for this study over a period of 1 year. Group 1 included 38 hysterectomised women being treated with continuous transdermal oestradiol only (50 microg daily). Group 2 included 24 menopausal women with an intact uterus being treated with transdermal oestradiol (50 microg daily) and medroxyprogesterone acetate (10 mg daily for the first 12 days of each calendar month). Women maintained on 50 microg oestradiol throughout 6 months (group 1: n = 22; group 2: n = 16) were reviewed for changes in serum lipids and lipoproteins at the end of 6 months (group 1), and between days 8 and 12 of the seventh month (combined phase of treatment) (group 2). RESULTS: In group 1, there was a small reduction in the concentrations of total cholesterol (-5.5%, P = 0.04) and a small but not significant reduction in LDL-cholesterol (-5.7%, P = 0.16). In group 2, there were no significant changes in total cholesterol (-4.2%, P = 0.43) and LDL-cholesterol (-3.9%, P = 0.57). HDL-cholesterol levels did not change significantly with unopposed transdermal oestradiol (+3.0%, P = 0.53), or with additional sequential medroxyprogesterone acetate (-3.8%, P = 0.32). Serum triglyceride concentrations decreased significantly in both the groups (-13.9%, P = 0.01, and -13.4%, P = 0.008, respectively). Serum lipid changes did not differ between the groups. CONCLUSIONS: Transdermal oestrogen therapy appears to be of particular benefit for women with hypertriglyceridaemia. There were no significant adverse effects of medroxyprogesterone acetate on serum lipids and lipoproteins.

Administration, Cutaneous↗

Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17beta-estradiol and norethindrone acetate.

OBJECTIVE: We studied bleeding patterns in postmenopausal women who were using 2 types of continuous combination regimens. STUDY DESIGN: A prospective, double-blind, randomized study of 208 postmenopausal women treated with conjugated estrogen, 0.625 mg, and medroxyprogesterone acetate, 5 mg, or with 17beta-estradiol, 2 mg, and norethindrone acetate, 1 mg. RESULTS: The mean number of bleeding days decreased during the first 4 months of treatment (P <.002) but not thereafter. The number of bleeding days was fewer (P <.002) and the time until amenorrhea was shorter (P <.02) in patients receiving conjugated estrogen and medroxyprogesterone acetate than in patients receiving 17beta-estradiol and norethindrone acetate. The odds ratio for progression to amenorrhea with the use of conjugated estrogen and medroxyprogesterone acetate was 1.58, in comparison with the use of 17beta-estradiol and norethindrone acetate. A thick endometrium at the start of treatment resulted in more bleeding days than were found for a thin endometrium (P <.03). Body mass index, age, and blood pressure had no predictive value for bleeding problems. CONCLUSIONS: Treatment with continuous combined conjugated estrogen and medroxyprogesterone acetate resulted in fewer bleeding problems than did treatment with 17beta-estradiol and norethindrone acetate. Endometrial thickness may help to predict the chance of achieving amenorrhea during early hormone replacement therapy.

Aging↗

Results of a dose-intense phase 1 study of a combination chemotherapy regimen with cisplatin and epidoxorubicin including medroxyprogesterone acetate and recombinant interleukin-2 in patients with inoperable primary lung cancer.

Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.

Adult↗

Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats.

OBJECTIVE: To examine whether chronic administration of the natural hormone progesterone or a synthetic progestogen, medroxyprogesterone acetate, to ovariectomized rats affects the endothelial control of arterial tone in the isolated mesenteric artery. DESIGN: Sham-operated rats received a daily subcutaneous injection of solvent (sesame oil), whereas ovariectomized rats received either sesame oil, progesterone (22 mg kg/day), or medroxyprogesterone acetate (22 mg kg/day) for 4 weeks, according to their respective group. RESULTS: Phenylephrine-induced contractions were significantly increased (about 200% at 10 microM) by N-nitro-L-arginine, a nitric oxide synthase inhibitor, in intact mesenteric arterial rings from the sham-operated but not from the ovariectomized group. The progesterone but not the medroxyprogesterone treatment restored the potentiating effect of N-nitro-L-arginine on phenylephrine-induced contraction (about 180% at 10 microM). Contractions to phenylephrine were not affected by the combination of charybdotoxin plus apamin, two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses, in all groups. Acetylcholine induced endothelium-dependent relaxations, which were partially inhibited by N-nitro-L-arginine and abolished by the combination of N-nitro-L-arginine plus charybdotoxin and apamin, in all groups. Acetylcholine induced similar charybdotoxin and apamin-sensitive hyperpolarizations in intact mesenteric artery segments from all groups. CONCLUSIONS: Chronic administration of progesterone, but not medroxyprogesterone, to ovarictomized rats restores the endothelium-dependent attenuation of contractile responses to phenylephrine in mesenteric arterial rings through the endothelial formation of nitric oxide. Thus, an enhancement of the protective effect of endothelial cells on the arterial wall might contribute to the beneficial effect of certain progestogen-containing preparations during hormonal treatment.

Animals↗

Enzymes of collagen synthesis and type III procollagen aminopropeptide in the evaluation of D-penicillamine and medroxyprogesterone treatments of primary biliary cirrhosis.

Changes in serum immunoreactive prolyl hydroxylase protein (IRPH), galactosylhydroxylysyl glucosyltransferase activity (GGT) and the aminoterminal propeptide of type III procollagen [Pro(III)-N-P] were studied in 21 patients with primary biliary cirrhosis during a follow-up period of up to three years. The patients received either D-penicillamine (600 mg/day), medroxyprogesterone acetate (5 mg/day), or a placebo, or no treatment after the D-penicillamine or medroxyprogesterone medication, each period lasting from nine to 15 months. The individual serum IRPH, GGT, and Pro(III)-N-P concentrations exceeded the upper normal limit in most patients. No significant changes were found in any of these three serum markers during any of the five different periods, nor was there any evidence for a decrease in the raised prolyl 4-hydroxylase activity in the hepatic biopsy specimens in response to any of the treatments. Galactosylhydroxylysyl glucosyltransferase activity decreased significantly in these specimens during medroxyprogesterone therapy, but the interpretation of this, the only positive change, remains unclear. The data suggest that D-penicillamine or medroxyprogesterone therapy may have no favourable effect on the increased hepatic collagen formation involved in primary biliary cirrhosis.

Adult↗

Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial.

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.

Adult↗

Medroxyprogesterone and palliative care: new indication. No impact on quality of life.

(1) Oral medroxyprogesterone has been granted a new licence in France for the treatment of weight loss and loss of appetite in patients receiving palliative care for cancer. (2) The clinical file on medroxyprogesterone in this indication is limited. A large number of patients were excluded from the final assessments in the three published placebo-controlled trials. (3) Overall, these trials show that 12 weeks of treatment with medroxyprogesterone 300-1,000 mg a day orally is associated at best with median weight gain of 3 kg, or weight stabilisation, but with no effect on quality of life. (4) Although no cases of thrombosis were reported in the clinical trials, the risk of thrombosis cannot be ruled out in medroxyprogesterone therapy.

Antineoplastic Agents, Hormonal↗

[Conservative surgery combined with depot medroxyprogesterone acetate in treatment of moderate or severe endometriosis].

OBJECTIVE: To evaluate the efficiency and side-effects of depot medroxyprogesterone acetate in the treatment of moderate or severe endometriosis after conservative surgery. METHODS: Ninety-four women with moderate or severe endometriosis after conservative surgery were divided into three groups: 34 cases in the group of depot medroxyprogesterone acetate (DMPA) received intramuscularly depot medroxyprogesterone acetate 150 mg every 28 - 30 days for 6 months; 30 cases in the group of gonadotropin releasing hormone agonists (GnRH-a) received hypodermically leuprorelin acetate 3.75 mg every 28 - 30 days for 6 months; 30 cases in the group of control did not receive any postoperative medical treatment. Patients' symptoms and signs including pelvic pain, pelvic tenderness, menstrual and weight changes were recorded before and after treatment. Liver and renal functions, sex hormone level were also examined at the same time. RESULTS: Both DMPA and GnRH-a treatment achieved similar significant relief of pelvic symptoms and signs (88% and 93%) compared with the control group (chi(2) = 12.273, P < 0.01; chi(2) = 9.604, P < 0.01). The cumulative recurrence rates of DMPA and GnRH-a groups were 6% and 7%, significantly lower than that of the control group (chi(2) = 5.222, P < 0.05; chi(2) = 4.320, P < 0.05). There were no significant differences between DMPA and GnRH-a groups (chi(2) = 0.488, P > 0.05; chi(2) = 0.017, P > 0.05). Serum estradiol (E(2)) level was significantly reduced in both DMPA and GnRH-a groups, but serum E(2) was maintained at the level of early follicular phase in the group of DMPA (120 +/- 9) pmol/L and menopause phase level in the group of GnRH-a (62 +/- 9) pmol/L. The main side effects of DMPA were menstrual changes, weight gain and delay of ovulation. CONCLUSION: Depot medroxyprogesterone acetate seems to be an effective, safe, and convenient treatment for endometriosis with low-cost, good compliance, and few side effects.

Adult↗

Oral medroxyprogesterone in the treatment of postmenopausal symptoms.

A double-blind crossover study was designed to compare the effects of placebo and medroxyprogesterone acetate, 20 mg, on vasomotor flushes and blood hormones in 27 postmenopausal women. In women receiving placebo, vasomotor flushes were decreased by 25.9% during the last four weeks of treatment compared with baseline, and a further decrease of 34.5% was achieved by the last four weeks after patients were given medroxyprogesterone. In women who initially took medroxyprogesterone, there a 73.9% decline by the last four weeks in the number of vasomotor flushes. However, when these women were given placebo, an immediate worsening of their symptoms occurred. The drug produced a decline of 27% and 29% in serum levels of follicle-stimulating hormone and luteinizing hormone, respectively, while the serum prolactin level rose slightly. Thus, medroxyprogesterone can be used to treat the vasomotor flushes of postmenopausal women when estrogen use is undesirable.

Administration, Oral↗

Risk of breast, uterine corpus, and ovarian cancer in women receiving medroxyprogesterone injections.

Animal studies have yielded conflicting results on the carcinogenicity of long-acting progestins. Since more than 1.5 million women worldwide are currently receiving injections of a contraceptive progestin, depot medroxyprogesterone acetate, this is potentially an important public health problem. We obtained information on the occurrence of breast, uterine, and ovarian cancer among 5,000 black women attending a metropolitan hospital's family planning clinic who had received injections of medroxyprogesterone for contraception (between 1967 and 1976). The women were followed up for four to 13 years after their initial medroxyprogesterone injection. We compared the observed number of cancer cases in these women with the expected number based on annual age-, race-, and sex-specific rates derived from National Cancer Institute data. During more than 40,000 woman-years of observation, we found no evidence of an increased risk of developing cancer of the breast, uterine corpus, or ovary in these women. After adjusting for possible underascertainment of cancer because of incomplete follow-up, we found the relative risk for medroxyprogesterone users to be 0.7 for breast cancer (95% confidence limits, 0.3 to 1.4), 1.2 (95% confidence limits, 0.1 to 6.7) for cancer of the uterine corpus, and 0.8 (95% confidence limits, 0.1 to 4.6) for ovarian cancer.

Adolescent↗

The ultrastructural response of human endometrium to medroxyprogesterone acetate.

Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.

Adult↗

The effect of depot-medroxyprogesterone acetate on the fetus and nursing infant: a review.

Data from published studies of the quantity of medroxyprogesterone acetate and/or its metabolites in the milk of lactating women receiving Depo-Provera for contraception is extrapolated into the amount of drug ingested daily by a theoretically average infant. Comparisons are made with the results of similar studies in animals. Fetal metabolism of medroxyprogesterone acetate is reviewed. Embryonic and fetal development of the human reproductive system is discussed. Results of studies of the effects of steroidal hormones, particularly medroxyprogesterone acetate, on mental development and sexual dimorphic behavior after exposure in utero are presented. It is concluded that the very small amount of drug and/or its metabolites ingested by the nursing infant via breast milk is highly unlikely to have any significant effect on the nursing infant.

Animals↗

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.

Journal Article↗