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PubMed1987

Growth hormone, insulin, glucose, cortisol, luteinizing hormone, and diabetes in beagle bitches treated with medroxyprogesterone acetate.

Adult beagle bitches (20 to 101 months old) received medroxyprogesterone acetate (MPA; 75 mg/kg, im) or control vehicle at 3 month intervals. Changes in serum concentrations of GH, insulin and glucose were determined in 18 MPA-treated and 6 of 12 control bitches at 0, 2, 4, 8, 16 and 17-24 months of treatment (Exp. I). GH, LH and cortisol responsiveness to combined im injection of TRH (10 micrograms/kg), GnRH (10 micrograms/kg), and ACTH (5 micrograms/kg) was determined in 9 MPA-treated and 9 control bitches at 17 months of treatment (Exp. II). In Exp. I, serum concentrations of GH at month 2 (2.6 +/- 0.3 micrograms/l), 4 (3.0 +/- 0.3 micrograms/l), 8 (4.0 +/- 1.2 micrograms/l), 16 (8.5 +/- 1.7 micrograms/l), and 17-24 (21.2 +/- 4.1 micrograms/l) of treatment were greater (P less than 0.05) than pretreatment (1.4 +/- 0.07 micrograms/l) and control (1.5 +/- 0.1 microgram/l) levels. The increase in GH at 2 months preceded (N = 4) or coincided (N = 2) with the development of hyperinsulinaemia and insulin resistance in 6 of the 18 treated bitches, two of which became diabetic by 17 months of MPA treatment. GH (24.6 +/- 5.0 vs 11.4 +/- 2.1 micrograms/l) and insulin (308 +/- 77 vs 119 +/- 9 pmol/l) concentrations were greater (P less than 0.05) in older (49 +/- 4 months; N = 12) than in the younger (26 +/- 2 months; N = 6) treated bitches at 17-24 months of MPA treatment. In Exp. II, pretreatment concentrations of GH were increased (9.8 +/- 3.0 vs 1.4 +/- 0.1 micrograms/l, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Effects of neonatal medroxyprogesterone acetate on postnatal sexual differentiation of female rats.

Medroxyprogesterone acetate (MPA), 5 micrograms/g body wt, was given to lactating female rats 1 day after parturition. Group 1 females suckled 10-12 young, with equal numbers of males and females, while Group 2 females each suckled 10 female young. The young were weaned at 21 days of age. Exposure to MPA advanced the day of vaginal opening by 1 day, and increased anogenital distance in Group 2 young. At autopsy between 80 and 100 days of age, the clitoris of Group 2 females was significantly greater than in controls, and ovarian and adrenal weights were reduced.

Adrenal Glands↗

PubMed1990

Medroxyprogesterone acetate for lung cancer.

A 70-year-old man having severe ischemic heart diseases developed bilateral, duplicate lung cancer of large cell and squamous cell types. Chemoimmunotherapy consisting of carmofur, picibanil inhalation, i.m. sizofilan, and peroral bestatin was started, and 3 months later, peroral medroxyprogesterone acetate was added. The tumor regressed, and the patient survived more than 34 months. This type of nonaggressive regimen may thus be useful for tumors other than adenocarcinomas, too.

Aged↗

PubMed1985

Medroxyprogesterone acetate does not perturb the profile of steroid metabolites in urine during pregnancy.

The plasma concentrations of medroxyprogesterone acetate (MPA) in 14 women administered the progestagen for threatened abortion during the first 6 weeks of pregnancy were measured by specific radioimmunoassay. Treatment (52 nmol orally every 6 h) was continued to 18 weeks of gestation. The mean plasma concentration of MPA rose rapidly during day 1 of treatment to 14.1 +/- 1.84 nmol/l. It reached 21.5 +/- 2.3 nmol/l by 7 days and subsequently stabilized at around 26.8 +/- 5.0 nmol/l by the end of week 2. Urinary steroid profiles were determined by gas-liquid chromatography and mass spectrometry for six of the MPA-treated women and compared with those of six untreated women of similar gestational age. No differences were detected between the two groups of women, suggesting that the administration of MPA during pregnancy did not alter qualitatively or quantitatively the metabolism and excretion into urine of progesterone and oestrogens.

Abortion, Threatened↗

PubMed1985

Changes in total and free concentrations of steroid hormones in the plasma of women throughout pregnancy: effects of medroxyprogesterone acetate in the first trimester.

The total (protein-bound plus free) and free concentrations of progesterone, oestradiol-17 beta and cortisol were measured serially throughout pregnancy in the plasma of two groups of women whose pregnancies went to term. Group A (n = 53) experienced an uneventful low-risk pregnancy with a spontaneous abortion rate of 8.6%. Women in group B (n = 22) were treated orally with medroxyprogesterone acetate (MPA; 80-120 mg daily) until 18 weeks gestation for threatened abortion within the first 6 weeks of pregnancy. In both groups of women the proportion of each hormone circulating in the free or unbound form remained constant despite the overall increases with occurred in total circulating hormone concentrations as pregnancy progressed. The steroid hormonal profiles in the first half of pregnancy were similar in both groups of women. However, from weeks 20 to 40 total and free progesterone concentrations were significantly (P less than 0.05 in each case) higher in group B compared with group A. Conversely, total and free oestradiol-17 beta concentrations were lower (P less than 0.005 and P less than 0.01 respectively) in group B. At this stage it is not known if these differences were attributable to the administration of MPA to women in group B or to altered placental steroidogenesis as a result of earlier uterine bleeding.

Abortion, Spontaneous↗

PubMed1990

Initiation of parturition and lactation in the sow: effects of delaying parturition with medroxyprogesterone acetate.

The synthetic progestagen, medroxyprogesterone acetate (MPA), was administered to sows in late pregnancy with the objective of slightly delaying the time of farrowing and thereby providing more marked associations between hormonal changes and the termination of pregnancy, and the initiation of farrowing and lactation in this species. MPA was administered orally (140 mg, twice daily) to eight sows in late pregnancy on days 112, 113 and 114 of gestation. Parturition was then induced to occur on day 116 by injecting 200 micrograms cloprostenol i.m. on day 115 of gestation. The peripartum changes in the plasma concentrations of progesterone, cortisol, oestradiol-17 beta, relaxin, prolactin, lactose and 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM) were measured in these sows together with a group of untreated sows. The gestational length for the MPA-treated sows (116.3 +/- 0.3 days, mean +/- S.E.M.) was significantly (P less than 0.01) greater compared with the untreated sows (114.9 +/- 0.3 days). Plasma progesterone declined earlier (P less than 0.05) with respect to the time of parturition in the treated sows compared with the untreated group. With respect to the timing of parturition, the time at which maximal concentrations of relaxin were attained and the timing of the subsequent decline were earlier in the MPA-treated sows. In both groups of sows, the concentration of relaxin increased before the decline in plasma progesterone. In the untreated sows, the concentration of PGFM increased either slightly before or at the same time as the decline in plasma progesterone, whereas in sows treated with MPA, progesterone concentrations began to decline before any significant increase in the plasma concentration of PGFM. The profiles of cortisol, oestradiol-17 beta and PGFM were similar in both groups of sows. In both groups of sows, the timing of the initial increase in the concentration of plasma prolactin coincided with a similar rise in plasma lactose (P less than 0.01). Plasma progesterone either declined earlier or at the same time as the rise in plasma lactose (P less than 0.01) in the treated group of sows only. We conclude that since the prepartum changes in the concentration of progesterone and relaxin occurred before significant changes in the concentration of PGFM in the MPA-treated sows, the nature of the luteolytic factor and the mechanism by which it exerts its action remains obscure. The higher concentration of lactose in the mammary secretion at birth in the MPA-treated sows compared with the untreated group suggested that lactogenesis was initiated earlier with respect to parturition following MPA treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

A seven-day synchronization method for ewes using medroxyprogesterone acetate (MAP) and prostaglandin F2 alpha.

Estrous cycles of adult (n = 27), farm-flock, Suffolk ewes and Polypay range ewes (n = 224) were controlled with medroxyprogesterone acetate (MAP)-impregnated vaginal pessaries inserted (d 0) for 7 d in combination with prostaglandin F2 alpha (PGF2 alpha) injected on d 6. Descriptive criteria of the effects of this treatment regimen on endocrine characteristics of the estrous cycle were evaluated in the experiment with farm-flock ewes. The efficacy of this synchronization regimen on reproductive performance of range-bred ewes was tested in a second trial. Suffolk ewes bred at the second observed estrus after treatment to provide comparisons of cycle length between treated and control ewes. Polypay ewes were exposed to fertile rams at the controlled estrus. Eighty-nine percent of Suffolk ewes were in estrus within 3 d after pessary removal. All nonsynchronized Suffolk ewes (n = 24) were in estrus over a 21-d period. Estrous cycle lengths of treated ewes averaged 16.8 +/- .2 d. Plasma progesterone concentrations were similar for treated and control ewes during the luteal phase of the estrous cycle. Ninety-one percent of the range-bred, controlled ewes lambed. Sixty-two percent of these ewes lambed within 150 d after exposure to fertile rams compared with only 17% of nonsynchronized ewes (P less than .05). Lambing percentage was similar by 167 d for treated (87%) or control (88%) ewes. Lambs per ewe exposed averaged 1.68 and 1.80 for treated and nonsynchronized groups, respectively. These data indicate the effectiveness of this 7-d treatment method for control of the estrous cycle of ewes during the normal breeding season. Results further show that this treatment scheme has practical application for range breeding of ewes.

Animals↗

PubMed1977

Endometrial histology and circulating levels of medroxyprogesterone acetate (MPA), estradiol, FSH and LH in women with MPA induced amenorrhoea compared with women with secondary amenorrhoea.

Circulating levels of medroxyprogesterone acetate (MPA), estradiol, progesterone and gonadotropins were determined in 11 women on long-term treatment with depot-MPA (Depo-Provera DMPA) 150 mg i.m. every 12th week as a contraceptive. The women had amenorrhoea due to the treatment. Endometrial biopsy was performed one week after injection and at the end of the 12 week period. Blood samples were taken on the same occasions. The findings were compared with those in 12 untreated women having secondary amenorrhoea. MPA was still detectable in serum and the end of the 12 week period. Endometrial biopsies showed gestagenic effects in the second as well as in the first biopsy. No MPA was detectable in the untreated women with amenorrhoea, and no gestagenic effects could be demonstrated in their biopsies. The estradiol levels in the DMPA group were in the range of the early follicular phase of a normal menstrual cycle and showed a significant rise at the end of the 12 week period. On the last sampling occasion the estradiol levels did not differ from those in the untreated women with secondary amenorrhoea. The levels of progesterone and gonadotropins were in the range of the early follicular phase in both groups. These observations support that DMPA 150 mg i.m. every 12th week is a depotpreparation with prolonged effect, and inhibits ovulation and produces endometrial changes by means of biologically active serum concentrations throughout the 12 week period.

Adult↗

PubMed1991

Serum lipids and lipoproteins during therapeutic amenorrhea induced by lynestrenol and depot-medroxyprogesterone acetate.

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were determined in mentally handicapped subjects (n = 87). 33 women were on lynestrenol 5-10 mg for therapeutic amenorrhea (TA). 18 of them were randomly allocated to continue on lynestrenol and 15 were switched to intramuscular administration of medroxyprogesterone (DMPA). The switch to DMPA resulted in significant increases in HDL-C (33%), Apo A1 (12%), as well as in the HDL-C/LDL-C (48%) and Apo A1/Apo B (22%) ratios. The concentrations of HDL-C and Apo A1 were significantly greater in patients receiving DMPA, than in patients continuing with lynestrenol therapy. The amenorrhea incidence, however, did not differ between the two therapy groups. It is concluded that therapy with DMPA may be associated with smaller atherosclerosis risk than with peroral lynestrenol, because of its weaker effect on HDL-C and A1 levels.

Adult↗

PubMed1978

High dose medroxyprogesterone-acetate treatment in advanced mammary carcinoma. A phase II investigation.

In a phase II investigation of high dose medroxyprogesterone treatment of advanced and previously with other methods heavily treated patient with mammary carcinoma, 7 of 25 patients had a partial remission with a median duration of 5 + months. In a further 7 patients the disease became stationary. As measured by Karnofsky's scale, a median improvement of 20 points was obtained in these 14 patients. In 4 of 15 patients who had not responded to Tamoxifen treatment, a partial remission occurred following MAP therapy. The patients tolerated MAP well.

Adult↗

PubMed1989

Adjuvant treatment with high dose medroxyprogesterone acetate in node-negative early breast cancer. A 3-year interim report on a randomized trial (I).

After initial surgery, 240 pre-, peri- or postmenopausal patients with early node-negative breast carcinoma were randomized to receive either no hormone therapy or adjuvant therapy with medroxyprogesterone acetate at high dosage (HD-MPA; 500 mg IM per day times 28 or 500 mg intramuscularly (i.m.) 5 days a week for 5 weeks then 500 mg i.m. twice weekly for the 5 following months. After a median follow-up time of 3 years, relapse-free survival and overall survival appeared significantly improved in the HD-MPA arm. Side effects were tolerable.

Adult↗

PubMedDate not supplied

Effect of medroxyprogesterone acetate upon PHA, Con A and PWM stimulated lymphocytes and on E-rosette function.

We evaluated if Medroxyprogesterone acetate (MPA) had an immunosuppressive action as progesterone and other steroid hormones. Lymphocyte function was evaluated by the blastogenic response to mitogens and by the E-rosette test. MPA was tested at 7 ng/ml and 100 ng/ml concentrations. Cells were either preincubated for 30 min., 90 min., 180 min. and 12 hr or incubated with MPA for 72 hr, 18 hr and 16 hr. MPA showed a significative inhibitory effect only when used at the concentration of 100 ng/ml.

Cells, Cultured↗

PubMed1987

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis.

A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis.

Adult↗

PubMed1987

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery.

To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.

Analysis of Variance↗

PubMed1992

[Antiproliferative actions of medroxyprogesterone acetate (MPA) to human ovarian cancer cell lines in vitro].

The cytostatic effect of medroxyprogesterone acetate (MPA; an oral luteohormone preparation) on two cell lines of ovarian carcinoma cultured in vitro (SHIN-3 and MN-1) was studied. At the same time, changes in the morphology and colony formation of these cancer cells after exposure to the drug were examined. 1) The doubling time of SHIN-3 cells in the logarithmic growth phase was prolonged 2.5 times at a MPA dose of 10(-8)M and 3.2 times at a MPA dose of 10(-5)M. The drug, however, exerted no significant cytostatic effect on MN-1 cells. 2) When the IC50 of MPA was assessed by counting live SHIN-3 cells in an FCS-added medium, it was 2.7 x 10(-5)M. When the same assessment was done with a medium without serum, IC50 was 6.4 x 10(-6)M. 3) After 120 hours of incubation in a medium containing 10(-8)M of MPA, CA125 (a tumor marker) production by SHIN-3 cells was suppressed by 35%. The suppression rate was 79% for SHIN-3 cells incubated in a medium containing 10(-5) of MPA. 4) The cytoplasm of SHIN-3 cells, incubated in a MPA-added medium, showed the formation of small mucous vacuoles and expansive degeneration, accompanied by a marked increase in size and thinning of the nucleus. 5) In an experiment on colony formation with collagen gel, the colony size decreased MPA concentration dependently, and was accompanied by the appearance of lobulated colonies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Mucinous↗

PubMed1992

Cholelithiasis associated with medroxyprogesterone acetate therapy in men.

Five out of forty-five adult men, 50 years of age or less, who had received, for at least six months, medroxyprogesterone acetate (MPA, Depo Provera) IM, 200-400 mg/week, for prevention of sex-offending or genital-mutilating behavior developed symptomatic cholelithiasis. Thirty of these men were studied with gallbladder ultrasound prospectively off MPA and at six-month intervals while taking the medication and then six months off MPA. Gallstones recovered from two patients were found to have very high cholesterol content, suggesting they were formed in cholesterol supersaturated bile. These findings are consistent with the increased incidence of gallbladder disease related to high-progesterone states and suggest that MPA may be a causative agent in cholelithiasis. The physiologic studies on gallbladder contraction and cholecystokinin release in a subset of the patients failed to provide information on a mechanism for the possible increased incidence of gallbladder disease.

Adult↗

PubMedDate not supplied

Bioavailability of medroxyprogesterone acetate from three oral dosage formulations.

The bioavailability of three formulations of medroxyprogesterone acetate (MPA) was assessed in 30 healthy male volunteers in a three-way, open-label, cross-over-designed trial. Each subject received one Provera 500-mg tablet, one Farlutal 500-mg tablet, and one Provera 500-mg granule packet according to a randomized schedule, with each treatment separated by a 21-day washout period. Serum MPA levels were determined using both radioimmunoassay (RIA) and high-performance liquid chromatography techniques. Based on the results of RIA analysis, Farlutal tablets produced significantly lower serum MPA concentrations compared with Provera tablets at most sampling times, resulting in statistically lower AUC0-144 for the Farlutal tablet (544 vs 768 ng.hr/ml; -29.2%). The Farlutal tablet also had a significantly lower maximum concentration than the Provera tablet (27.8 vs 47.4 ng/ml; -41.4%). However, there was no significant difference in time of maximum concentration between the tablet formulations (3.71 vs 3.41 hr), indicating that the rates of absorption of the two tablet formulations were comparable. Provera granules provided significantly higher serum MPA levels than Provera tablets at 0.5, 1, 1.5, 2, and 6 hours, and the AUC0-144 for Provera granules was higher by 5.47% (810 vs 768 ng.hr/ml). There were no differences in terminal elimination rate constants among the dosage forms. No significant adverse events were noted during the trial. The relative bioavailabilities of Provera granules and Farlutal tablets were 105% and 71.2%, respectively, compared with Provera tablets.

Administration, Oral↗

PubMed1964

[TREATMENT OF THREATENED AND HABITUAL ABORTION WITH MEDROXYPROGESTERONE].

A clinical study was made of an oral form of medroxyprogesterone in a group of pregnant patients with signs of a threatened abortion or with a history of habitual abortions, under conditions very similar to those obtaining in general practice. The aim was to assess the agent's effectiveness, its harmlessness, and its effect on the pregnancy in respect of both the mother and the infant.During a 31-month period, 43 pregnant women were administered this drug. The overall result in terms of live and healthy babies was 70%. This result was somewhat lower than that expected on the basis of previous studies; both public and private patients were included and no selection of patients was attempted. There were no apparent harmful side effects to mother or infant or evidence of virilization of female infants; postmaturity was not a problem.

Abortion, Habitual↗