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PubMed1986

Hormone treatment of meningiomas: lack of response to medroxyprogesterone acetate (MPA). A pilot study of five cases.

Medroxyprogesterone acetate (MPA) has been used in high doses as hormone treatment for metastatic breast cancer. We treated five intracranial meningiomas with MPA expecting that MPA would reduce the volume or decrease the growth rate. All five patients were postmenopausal women, aged 47 to 73 years. Before treatment, the growth rate of each tumour was assessed by two consecutive CT scans (CT 1 and CT 2). Tumours 1 to 4, histologically benign meningiomas, grew slowly as the tumour volumes were not found to increase in 21 to 45 months between CT 1 and CT 2. Tumour 5 was an anaplastic meningioma the rapid growth of which was evident in 8 weeks between CT 1 and CT 2. After CT 2, MPA was given 1,000 mg intramusculary once weekly for 17 to 29 weeks until CT 3 which showed the response. Tumours 1 to 4 had neither reduced in volume nor developed necroses, and tumour 5 continued its fast growth at the same rate as before.

Aged↗

PubMed1990

Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer.

One-hundred and seventy patients with estrogen receptor positive (greater than or equal to 10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg x 1 daily (TAM), or with TAM 30 mg x 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg x 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

The induction of a hypercoagulable state by medroxyprogesterone acetate in breast cancer patients.

The effects of medroxyprogesterone acetate (MPA) on the mechanism of coagulation in postmenopausal patients were studied and compared with those of tamoxifen by a retrospective analysis. The coagulation test parameters tested included platelet count, bleeding time, clotting time, prothrombin time, activated partial thromboplastin time, and the levels of fibrinogen, fibrin degradation products, factor II, factor V, plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI) and alpha 2-plasmin inhibitor-plasmin complex (alpha 2-PI-P). A shortened APTT was noted and the levels of factors II, V, alpha 2-PI and alpha 2-PI-P were also out of the normal range during treatment in the MPA-treated group. However, these abnormal parameters recovered to within the normal range from 6 months or more after the commencement of treatment without any termination of drug administration. The patients were all asymptomatic. In contrast, a slight prolongation of bleeding time which persisted for more than 6 months was observed in the patients treated with tamoxifen. These data suggest that MPA causes a hypercoagulable state and that any change must be carefully monitored during treatment with either MPA or tamoxifen.

Antineoplastic Agents↗

PubMed1990

Effective therapy of glucocorticoid-induced osteoporosis with medroxyprogesterone acetate.

The effect of long-acting medroxyprogesterone acetate (MPA) on the trabecular bone density in patients with glucocorticoid-induced osteoporosis (GCO) was evaluated. Thirteen steroid-dependent asthmatic male patients with GCO were administered 200 mg MPA intramuscularly at 6-week intervals and 1 g of elemental calcium daily for a period of 1 year. Ten additional matched steroid-dependent asthmatic male patients received 1 g of elemental calcium daily (controls). All 23 patients involved in the study had vertebral trabecular bone densitometry (TBD) by quantitative computed tomography (QCT) at baseline and at 6 and 12 months into the study. A 17% increase in TBD was found in the MPA-treated patients at 1 year (from 68.5 +/- 5 to 80.2 +/- 4 mg K2HPO4/cc) in contrast to the control group who experienced a 21% decrease in TBD during the same period of time (from 80.5 +/- 7 to 63.7 +/- 8 mg K2HPO4/cc) (T = 6.90, P = 0.0001 df = 21). There were no significant changes in other parameters followed during the study in the MPA-treated group (serum calcium, phosphorus, magnesium, PTH, alkaline phosphatase, triglycerides, total and HDL cholesterol, urinary excretion of calcium, phosphate, creatinine) except for a decrease in the serum luteinizing hormone (LH) and testosterone (P less than 0.01) as well as of the hydroxyproline-creatinine ratio (P less than 0.01). The results lend support to the hypothesis of a progesterone-glucocorticoid competitive antagonism at the bone level, though other possibilities can be entertained, and suggest MPA as an effective therapy for glucocorticoid-induced osteoporosis in men.

Aged↗

PubMed1990

Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate.

To confirm that concomitant administration of aminoglutethimide (AG) reduces plasma levels of medroxyprogesterone acetate (MPA), MPA levels were assayed in six patients with advanced breast cancer receiving the two agents. Patients had disease resistant to AG and were studied during conversion to therapy with MPA. Hydrocortisone was discontinued at the commencement of study and MPA introduced and given at a constant dose of 800 mg daily while AG was reduced in dose from 250 mg b.d. to 125 mg b.d. and then discontinued. MPA levels were measured after two weeks at each dose of AG and after two weeks on MPA alone. Mean MPA levels showed a progressive and significant (P less than 0.01) rise as the AG dose was reduced--180 ng ml-1, 250 ng ml-1 and 740 ng ml-1 respectively. MPA levels were always in excess of the accepted therapeutic level of 100 ng ml-1 and plasma cortisol levels fell in parallel with the rise in MPA levels.

Adult↗

PubMed1981

Menopause, medroxyprogesterone and breathing during sleep.

Twenty-one postmenopausal women were monitored for sleep-disordered breathing and nocturnal oxygen desaturation to evaluate the contribution of progestational hormones to the occurrence of these sleep events. For approximately one month 11 subjects received 30 mg of medroxyprogesterone (MPG) daily, and 10 received placebo tablets in a randomized, double-blind controlled study. Respiration, saturation and electroencephalography were monitored during one night of sleep before and one night after therapy. Contrasted with the low incidence of disordered breathing and desaturation in premenopausal women, 71 percent of the postmenopausal women had such events. In the placebo-treated group, all measured variables of sleep and breathing were identical on the two nights, which suggested that the findings of a single night of sleep monitoring may be representative of other nights of sleep. Although several subjects appeared to show improvement with MPG, only the maximum duration of apnea was significantly reduced the second night (p less than 0.03).

Adult↗

PubMed1981

Objective evidence that placebo and oral medroxyprogesterone acetate therapy diminish menopausal vasomotor flushes.

The vasomotor flush (VMF) is the most common reason for menopausal women to seek hormonal therapy, but the evaluation of therapeutic regimens has been hampered by the observation that placebo therapy can decrease VMF and, until recently, by a lack of objective criteria of measurement of the VMF. Using the objective criteria of temperature elevations (TEs) and luteinizing hormone (LH) pulses, we evaluated the effect of placebo and medroxyprogesterone acetate (MPA) on VMF. MPA and possibly also placebo were found to reduce not only the subjectively noted VMF but also the frequency of TEs recorded. In addition, MPA, but not placebo, significantly reduced the frequency and amplitude of LH pulses. Possible mechanisms of action of MPA and placebo therapy are discussed.

Body Temperature↗

PubMed1985

The effect of medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes in normal and protein-deficient female rats.

Effect of depot medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes was studied in female protein-deficient and normal pair-fed rats. Treatment with this drug did not cause any change in organ weight, microsomal protein, and soluble protein yield per gram of tissue in both groups. MPA administration resulted in significant increases in the content of cytochrome P-450 and b5, and activities of benzo[a]pyrene hydroxylase, UDP-glucuronosyltransferase, and NADPH-Cyt c reductase in both pair-fed control and protein-deficient rats. However, the content of glutathione and activity of glutathione-S-transferase were not affected appreciably. The present study suggests that MPA treatment induces drug-metabolizing enzymes in liver to almost the same extent in both protein-deficient and normal pair-fed rats.

Animals↗

PubMed1983

Medroxyprogesterone acetate improvement of the hepatic drug-metabolizing enzyme system in rats after chemical liver injury.

Medroxyprogesterone acetate (MPA) has an inducing effect on the hepatic drug-metabolizing enzyme system in the rat. The effect of MPA on the liver metabolism was further evaluated here by investigating the restoration of hepatic function after chemical liver injury in female rats. The hepatic injury was induced by pretreating the animals with CCl4 and dimethylnitrosamine for 4 weeks, after which rats treated with MPA for a week were compared with rats showing spontaneous regeneration upon treatment with the MPA vehicle only. Changes in various parameters of the drug-metabolizing enzyme system were used as indices of hepatic function together with liver protein content. The results showed that MPA therapy increased the cytochrome P-450 content and the activity of NADPH-cytochrome c reductase, the monooxygenase enzymes benzo[a]pyrene hydroxylase and aminopyrine N-demethylase, epoxide hydrolase and glutathione S-transferase. MPA increased the relative values in the rats with liver injury almost equally to, or even more than, that seen in the intact animals in comparison to the corresponding vehicle-treated rats. MPA seemed to enhance protein synthesis during liver regeneration, as indicated by changes in total liver protein and in the gel electrophoresis pattern of the microsomal proteins. The hepatic enzyme induction and enhancement of protein synthesis achieved by MPA after liver injury may be of value in the treatment of liver diseases.

Animals↗

PubMed1979

Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters.

A potential male contraceptive approach was evaluated in clinical trials involving monthly injections of depot medroxyprogesterone acetate and either subdermal implants of testosterone propionate or monthly injections of testosterone enanthate. Pregnancies occurred in partners of 9 men with recent sperm counts of 10 million/ml or below. In 5 of the 9 instances, the sperm counts were less than 1 million/ml. It appears that male contraceptive methods involving spermatogenic suppression may require attainment and maintenance of azoospermia. The pregnancy rate cannot be calculated, because the extent of other contraceptive use is uncertain. There were no spontaneous abortions. 6 pregnancies were carried to term, and all progeny were normal, based on physical examination at birth or 3 months after birth.

Contraceptive Agents, Male↗

PubMed1980

Serum high density lipoprotein cholesterol levels in women using a contraceptive injection of depot-medroxyprogesterone acetate.

The mean serum high density lipoprotein cholesterol (HDL-C) concentration proved to be significantly lower in 23 women taking depot-medroxyprogesterone acetate (DMPA) as a twelve-weekly injectable contraceptive for at least 1 year, as compared to 23 IUD users. In the DMPA group, no significant difference was found in the mean serum HDL-C concentration, when measured 2, 6 and 12 weeks after a DMPA injection.

Cholesterol↗

PubMed1980

The association of depo-medroxyprogesterone acetate and breast cancer.

The use of depo-medroxyprogesterone acetate (DMPA) as an injectable contraceptive for women has continued to be controversial for over 10 years. The U.S. Food and Drug Administration has not approved it for contraceptive use but the World Health Organization has. We undertook a case-control study to clarify the possible association of breast cancer and DMPA use. Subjects were selected from women enrolled in the Grady Memorial Hospital Family Planning Clinic in Atlanta, Georgia, from 1967 to 1979. The risk of breast cancer in DMPA users compared to nonusers is identical. The small number of women with breast cancer, the short average exposure to DMPA, and the lack of detail about the subjects themselves caused us to interpret our results cautiously. However, it seems reasonable to conclude that short-term use of DMPA among black women is not associated with any increased risk of breast cancer.

Adult↗

PubMed1981

Efficacy of antibodies generated by Pr-beta-hCG-TT to terminate pregnancy in baboons: its reversibility and rescue by medroxyprogesterone acetate.

Antibodies produced by the vaccine Pr-beta-hCG-TT in monkeys were effective in terminating pregnancy in baboons on passive administration. The animals returned to cyclicity soon after the onset of vaginal bleeding. Fertility was regained. Globulins from non-immunized control monkeys in amounts, volume and injection schedule similar to those employed for passive termination did not intercept pregnancy. The abortifacient action of anti-CG antibodies could be counteracted by administration of medroxyprogesterone acetate.

Abortion, Induced↗

PubMed1982

A rapid method for the determination of 5 alpha-dihydrotestosterone in Thai males receiving medroxyprogesterone acetate.

A rapid method for the determination of DHT (5 alpha-dihydrotestosterone) in serum was established, utilizing potassium permanganate as an oxidising agent to convert the double bond at position 4-5 of testosterone to dihydroxy alcohols. DHT was then extracted with diethyl ether and measured directly using radioimmunoassay technique. The precision of the assay was determined at three levels of DHT added into pooled serum and found to be 4.4-5.1% for between assay percentage coefficient of variation. The sensitivity of the standard curve was found to be 4.2 pg/0.5 ml sample. The accuracy was determined in pooled serum with added standard DHT in the range of 80-800 pg. The percentage recovery of the assay was found to be 92.93-98.35%. The antisera used for DHT assay exhibited no significant cross-reaction with various steroids tested except testosterone which showed a 91.3% cross-reaction. The method was applied to measure the level of DHT in serum of Thai males receiving medroxyprogesterone acetate (MPA) as an oral contraceptive. Twenty-five subjects were divided into 5 groups. Group 1 received an oral placebo with monthly sesame oil injection. Groups 2, 3 and 4 received 5 mg, 10 mg and 20 mg MPA, respectively, with the addition of monthly injection of 250 mg testosterone enanthate (TE). Group 5 received 20 mg MPA daily with the addition of monthly injection of 500 mg TE. Blood specimens were obtained monthly. The first 4 months were used as a control period. After the 4-month period, each subject received treatment as mentioned above for 6 months, then follow-up study was resumed for another 6 months. The results revealed that subjects receiving 20 mg MPA with the addition of 250 mg TE showed a significant decrease of DHT levels (p less than 0.001).

Contraceptive Agents, Male↗

PubMed1985

Transient reduction in serum HDL-cholesterol following medroxyprogesterone acetate and testosterone cypionate administration to healthy men.

Serum lipids were examined in thirty normal male volunteers who had received depo-medroxyprogesterone acetate (DMPA) and testosterone cypionate (TC) in a male contraceptive trial. Progestagens have been implicated in the changes in serum lipids observed in women using oral contraceptives and this has led to concern about cardiovascular health risks associated with the long-term use of some of these preparations. The following study was done to determine if similar effects occur in men. The men in this study were divided into three DMPA dose groups (50, 100, 200 mg/month) and received intramuscular injections for six months; all men received 250 mg/month TC. There was no significant change in serum high density lipoprotein-cholesterol (HDL-C) levels during the six months of drug administration when compared to levels in the control period. However, there was a marked decrease in HDL-C during the first three months after discontinuation of the drugs (p less than 0.02). This observed change was consistent in each of the three DMPA dose groups but no dose relationship was observed. There was no statistically significant change in serum concentrations of total cholesterol, low density lipoprotein-cholesterol, triglycerides or insulin in any period of the experiment. Serum testosterone (T), estradiol, and sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH) concentrations were all significantly depressed during the drug administration period. A progestagen dose relationship was observed only for the decrease in serum testosterone and LH concentrations. Serum T and SHBG levels were still significantly reduced at 4-6 months after cessation of the drug administration. These findings demonstrate that DMPA can cause a reduction in serum HDL-C levels. It is suggested that HDL-C concentrations fell only following DMPA withdrawal as a consequence of steroid hormone changes specific to this period.

17-alpha-Hydroxyprogesterone↗

PubMed1986

A multicentred phase III comparative clinical trial of depot-medroxyprogesterone acetate given three-monthly at doses of 100 mg or 150 mg: 1. Contraceptive efficacy and side effects. World Health Organization Task Force on Long-Acting Systemic Agents for Fertility Regulation. Special Programme of Research, Development and Research Training in Human Reproduction.

Two dosages of depot-medroxyprogesterone acetate (DMPA), 100 mg and 150 mg given every 90 days, were compared in two groups of women with regard to effectiveness, reported complaints and reasons for discontinuation. A total of 1216 women were recruited into a seven-centre, multinational, randomized clinical trial. Follow-up was for a period of one year and resulted in a total of 5507 woman-months of experience of 100 mg DMPA and 5429 woman-months of experience of the 150 mg dose. The study showed little difference in efficacy and side effects between the two treatment groups. Two pregnancies occurred in women receiving 100 mg DMPA giving a Pearl Index of 0.44 per 100 woman-years. None occurred in the 150 mg group. There was no difference in the overall continuation rates between the two groups at one year, being 59.3% in the 100 mg group and 58.8% in the 150 mg group. Except for discontinuation of method use for amenorrhea, the rates of all medical and non-medical reasons given for discontinuation were comparable between the two treatment groups. Women's perception of lack of bleeding was reported as amenorrhea and resulted in discontinuation rates at 12 months for amenorrhea of 7.2% for women receiving 100 mg of DMPA and 12.5% for those receiving the 150 mg dose. Three centres, Alexandria, Karachi and Szeged, made the major contributions to this difference.

Adult↗

PubMed1986

Pituitary, ovarian and endometrial effects of graded doses of medroxyprogesterone acetate administered on cycle days 7 to 10.

Eighteen apparently healthy women with normal menstrual cycles were studied during a control cycle and then during a treatment cycle, in which graded doses (2.5, 5.0 and 10 mg/day) of medroxyprogesterone acetate (MPA) were administered orally on cycle days 7 to 10. In both the control and the treatment cycle peripheral blood was drawn daily for the assay of luteinizing hormone (LH), estradiol (E2) and progesterone (PROG) and an endometrial biopsy was taken on cycle day 11. The lowest dose of MPA (2.5 mg X 4) did not influence the various cycle characteristics. Administration of higher doses (5.0 or 10 mg X 4) resulted in a lengthening of the duration of E2-peak (P less than 0.05), an increase in the area under the E2-peak (P less than 0.05), a decrease in the area under the PROG-curve (P less than 0.05) and a reduction in the height of the LH-peak (P less than 0.05). Furthermore, in 5 of these 12 subjects there was no ovulatory-like PROG-pattern during the cycle in which MPA was administered for 4 days. Morphometric analysis of the endometrial biopsy specimens revealed that the administration of MPA increased the diameter of endometrial glands (P less than 0.01) and the number of vacuolated glandular cells (P less than 0.001), decreased the number of glandular (P less than 0.01) and stromal (P less than 0.05) mitoses and reduced pseudostratification (P less than 0.001). There was no change in the number of endometrial glands and in glandular epithelial height. No leukocytic infiltration was observed. Dating of the biopsies indicated that all control biopsies were proliferative and all, but one (a suppressed proliferation including predecidual reaction), biopsies obtained after MPA administration were early secretory. The most conspicuous effect of MPA administration was a marked increase in subnuclear vacuolation, which could be demonstrated even at the lowest dose (P less than 0.01).

Adult↗

PubMed1990

Effect of depot medroxyprogesterone acetate and testosterone oenanthate on serum lipoproteins in man.

Ten normal men were given three monthly intramuscular injections of 200mg of depot medroxyprogesterone acetate (DMPA) and 250mg of testosterone oenanthate (TE) as part of a male contraceptive trial. During the three months of treatment, serum high density lipoprotein cholesterol (HDL-C) and the HDL-C:LDL-C (low density lipoprotein cholesterol) ratio were significantly depressed compared to baseline. Although the long-term effect of this alteration in lipoprotein cholesterol metabolism in normolipidaemic men is currently uncertain, these results suggest that the potential cardiovascular risks of progestagen-containing regimens for male contraception will have to be seriously considered.

Adult↗