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PubMed1983

Medroxyprogesterone acetate has opposite effects on the androgen binding protein concentrations in serum and epididymis.

In the rat, the effects of progestin and androgen administration on serum, testicular and epididymal androgen binding protein (rABP) concentrations were determined and related to the organ weight and morphology. Adult rats were treated with medroxyprogesterone acetate (MPA; 17 alpha-acetoxy-6 alpha-methylprogesterone), testosterone propionate (TP) and mibolerone (MB; 7 alpha, 17 alpha-dimethyl-19-nortestosterone). MPA reduced testicular and epididymal weights and the concentrations of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone. During MPA treatment testicular and epididymal ABP content declined in parallel with organ weights and hormone concentrations, whereas serum ABP concentrations increased. Combinations of MPA and TP reduced testicular and epididymal ABP, but the reductions were less than with MPA alone; this combined treatment also elevated serum AMP. Both MB and TP reduced ABP in the male reproductive tract, but unlike MPA did not increase the concentration of this protein in serum. The results suggest that MPA acts directly on Sertoli cells resulting in increased ABP release into the blood. The comparison was made of steady state polyacrylamide gel electrophoresis (SS-PAGE) and radioimmunoassay (RIA) methods of estimating rABP. The potency ratio of testicular ABP estimated by the two methods (RIA:SS-PAGE) was three times higher than this ratio in the epididymis in normal and hormonally treated animals. Due to differences in end points, these observations imply that these assays do not quantify the molecules in the same way in one or both of these tissues. The results indicate, however, that both assays are suitable for following rABP concentration in animals with altered hormonal states.

Androgen-Binding Protein↗

PubMed1988

High-dose medroxyprogesterone acetate plus mitomycin-C or vindesine in the treatment of advanced breast cancer.

Forty women with metastatic breast cancer were randomized to receive either mitomycin-C (MMC) (21 patients) or vindesine (19 patients) with high dose medroxyprogesterone acetate (MPA). Response rates were not significantly different (33% for MPA and MMC and 28% for MPA and vindesine); the duration of response was better for patients receiving the MMC combination (median of 10.5 months versus 6 months for those on the vindesine combination).

Adult↗

PubMed1989

Influence of tamoxifen-medroxyprogesterone sequential therapy on estrogen and progesterone receptor contents of breast cancer.

The influence of tamoxifen (TAM) and medroxyprogesterone acetate (MPA) sequential administration on the estrogen receptor (ER) and progesterone receptor (PR) contents of breast cancer was studied in 68 patients with operable breast cancer. TAM was used as a primer of PR induction in order to enhance the effects of MPA. Half of the patients (n = 34) were preoperatively treated with TAM (20 mg/day for 7 days) and sequentially with MPA (1200 mg/day for 17 (median) days). ER and PR of surgical specimens were assayed by enzyme immunoassay and the results were compared with those obtained from the other half of the patients (n = 34), who had not received any treatment before surgery. TAM-MPA treatment significantly lowered PR in the cytosol regardless of the menopausal status. On the other hand, TAM-MPA treatment significantly lowered ER in the cytosol only in the postmenopausals but not in the premenopausals. These results demonstrate that reduction of ER provoked by TAM-MPA treatment is dependent on menopausal status.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Changes in hematologic parameters during treatment with medroxyprogesterone acetate for breast cancer.

To elucidate the etiology of the thrombogenic effects of high-dose medroxyprogesterone acetate (MPA) in the treatment of breast cancer, hematologic parameters were sequentially assessed in 12 patients receiving MPA 800 mg p.o. daily for 6 months as adjuvant hormone therapy after mastectomy. The results were as follows. (1) Coagulation system: levels of factor VII and fibrinogen decreased significantly, whereas factors II and IX increased significantly, with a shortened activated partial thromboplastin time. (2) Fibrinolytic system: plasminogen and alpha 2-plasmin inhibitor-plasmin complex increased, whereas fibrinogen degradation products remained low. (3) Anticoagulation system: antithrombin III increased significantly. (4) These changes were most marked after 2 or 4 weeks of MPA treatment, and returned to the pretreatment level one month after discontinuation of treatment. (5) No patients in this study developed thromboembolic disease during or after MPA administration. These results indicate that MPA may induce a hypercoagulable state, but this state does not directly lead to the development of thrombosis.

Adult↗

PubMed1985

Medroxyprogesterone acetate therapy in hirsutism.

In a pilot study, 26 hirsute females were treated with medroxyprogesterone acetate (MPA). We used an ointment containing 0.2% MPA in 13 patients, subcutaneous injection of MPA into the hairy areas of the face in five patients and intramuscular injection of low doses of MPA in 13 patients, each for an average duration of 16 weeks. The best clinical result was achieved by subcutaneous injection, the next most successful was the intramuscular injection, and the least successful was the topical application. Hair diameter measurements, carried out in 12 patients, were found to be reduced by 33% on average. Serum androgen levels, measured monthly, remained unaffected by topical treatment, but were decreased by intralesional and intramuscular injection. The clinical improvement with topical therapy despite the lack of effect on serum androgen levels supports the idea that MPA works partly at the cellular level. The intralesional and systemic injection of MPA may exert an effect both by systemic androgen suppression and a local action.

Administration, Topical↗

PubMed1986

Effects of medroxyprogesterone acetate in women with polycystic ovary syndrome.

LH levels are inappropriately elevated in women with polycystic ovary syndrome (PCO). Regardless of whether this LH elevation is primary or secondary it may be involved in the establishment of chronic anovulation. We have therefore tried selectively to suppress LH by giving medroxyprogesterone acetate (MPA) 5 mg twice daily for 14 d to 13 women with PCO (14 studies) and have examined their pituitary and ovarian response to assess whether follicular development and ovulation would be triggered post-treatment as a result of secretion of endogenous gonadotrophins in a more nearly physiological ratio. Blood samples were obtained before and two to three times weekly during and after treatment for 35-50 d. In two of these cycles MPA was started fortuitously during the luteal phase of a spontaneous cycle. In the remainder, three patterns of response were seen. In 9 cycles, after an initial rise, there was a progressive fall in gonadotrophin levels, LH (mean 48% of basal) more than FSH (mean 68% of basal); after MPA was stopped FSH levels recovered more rapidly than LH. In two cycles (one subject) MPA administration was associated with a progressive rise in serum oestradiol and progesterone. In a further cycle, treatment was also accompanied by an oestradiol rise and was followed by establishment of regular ovulatory cycles. The observed differential suppressive effect on LH and FSH levels suggests that MPA might be of therapeutic value if followed by treatment with anti-oestrogens or exogenous gonadotrophins in PCO.

Adolescent↗

PubMed1981

Sperm suppression with monthly injections of medroxyprogesterone acetate combined with testosterone enanthate at a high dose (500 mg).

The combination of an initial injection of 1000 mg of depot medroxyprogesterone acetate and 500 mg of testosterone enanthate, followed by monthly administration of 150 mg and 500 mg of the same drugs, was tested in 10 healthy males aged 28 through 39, with pre-treatment sperm counts of 50 x 10(6)/ml or more. Eight of the subjects achieved azoospermia, and the sperm counts of the other two declined 0.09 ad 5 million/ml. This last subject was highly refractory to treatment as his sperm density recovered to 27 million sperm/ml at the 6th month of continuous therapy. FSH was severely depressed during the entire treatment period. LH fell to 30--40% of normal values in the first two months and then showed a slow recovery during maintenance treatment. Testosterone measured one month after each injection was between 10 and 30% of pre-treatment values. Three of the subjects had increased libido and potency, none had decreased sexual drive or potency. All subjects gained weight with the average gain being 6 kg. The increase in the dose of testosterone enanthate to 500 mg/ng did not improve the results as compared to previous trials using lower doses of TE.

Adult↗

PubMed1988

Endocrine, seminal and peripheral effects of depot medroxyprogesterone acetate and testosterone enanthate in men.

Depot medroxyprogesterone acetate (D-MPA, 250 mg) and testosterone enanthate (TE, 200 mg) were administered twice with a 4-week interval to nine healthy men, and the levels in blood of steroids, gonadotrophins, lipoproteins, sex hormone binding globulin (SHBG) and prostaglandins (PGs) were measured, as well as steroid levels in semen and the sperm count and motility. The hormones analysed were: MPA, testosterone, androstenedione (A), dihydrotestosterone (DHT), oestradiol (E2), cortisol (C), luteinizing hormone (LH), follicle stimulating hormone (FSH) and the sulphoconjugated forms (-S) of testosterone, DHT, pregnenolone (5-P) and dehydroepiandrosterone (DHEA). Peak values of MPA (10.2 +/- 4.6 nmol/l) and testosterone (28.0 +/- 10.0) were found in the first blood samples 2 days after each injection. Thereafter the levels of MPA decreased gradually and reached the limit of detection 18-20 weeks after the second injection. Blood levels of testosterone fell sharply from the peak values and were grossly subnormal 2 weeks after each injection; levels did not return to pretreatment values during 24 weeks of follow-up. The pattern of change of DHT, A, E2 and sulphonated androgens was similar to that of testosterone. These data suggest that D-MPA and TE are absorbed at similar rates, and that the TE is metabolized rapidly. The subsequent reduction in the levels of A, testosterone-S and DHT-S was less marked and reached pretreatment values earlier than did the testosterone levels. No obvious changes were found in the levels of C, 5-P-S and DHEA-S or in the seminal plasma levels of the various steroids studied. The blood levels of LH and FSH fell precipitously 2 days after the first injection, then started to increase 4 weeks after the second injection to reach pretreatment values 12 weeks later. Of the lipoproteins studied only the levels of HDL-cholesterol and SHBG were found suppressed after treatment. Severe oligozoospermia and the complete absence of progressively motile sperm, in at least one semen sample, was observed in all subjects at 3-7 and at 5-16 weeks, respectively, after the last injection, suggesting that the men were infertile for at least 1 month after treatment. A spurious increase in the PG content of semen was also observed. In spite of the low blood testosterone levels, no subject reported changes in sexual behaviour or other signs of anabolic imbalance during or after the study. However, the increase in levels of E2 in some individuals should be kept in mind as a possible cause of side-effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

The effects of medroxyprogesterone acetate and ethinylestradiol on hemogram, prostate, testes, and semen quality in normal dogs.

Three dogs were treated with medroxyprogesterone acetate (MPA) and three were treated with ethinylestradiol. The results indicate that at a dosage of 3-4.8 mg/kg b.w. MPA does not have any detrimental effects on hemogram, testicles or semen quality, whereas ethinylestradiol (2 micrograms/kg b.w./day) can negatively affect both testes and semen quality. Both drugs can cause a decrease in prostatic size in clinically healthy dogs. Measurements of peripheral serum testosterone levels indicate that at the dosages used, testosterone levels are depressed considerably more by ethinylestradiol than by MPA.

Animals↗

PubMed1987

Effects of medroxyprogesterone acetate on sleep of healthy young male adults.

The effects of a single 100 mg dose of medroxyprogesterone acetate (MPA) on human sleep were investigated using healthy young male adults. After a baseline night recording, two consecutive MPA nights and the following two withdrawal nights were recorded. The total sleep time was reduced after the 2nd MPA night and the decrease was significant on the 1st withdrawal night. The time of intrasleep awakening increased after the 2nd MPA night. Stage 1 sleep increased significantly on the 2nd MPA and 1st withdrawal nights. Stage 4 sleep decreased and the sleep latency gradually increased after the MPA administration. REM sleep reduced slightly on the 1st withdrawal night. These results indicate that MPA has a mild arousal action on human sleep and that the action may be pronounced a few days after administration of MPA.

Adult↗

PubMed1987

Medroxyprogesterone acetate and sleep apnea.

Seven patients with sleep apnea DOES and one with sleep apnea DIMS were treated with medroxyprogesterone acetate (MPA). The therapeutic effect was confirmed in most of them by polysomnographic recording. A marked increase of TST was observed in two patients whose AI and/or %SAT remarkably decreased. Contrarily, three patients exhibited a considerable decrease in TST, and AI and/or %SAT were reduced remarkably in two of them with MPA. After the MPA medication a few patients complained of disturbed nocturnal sleep. A significant positive correlation was observed between the decreased rate of TST and that of the mean duration of apneas. From these results, it was considered that MPA has a mild activating action on the arousal system in the CNS, and that the action may be partly responsible for the therapeutic effects of MPA on sleep apneas.

Adult↗

PubMed1989

Sequential alternating medroxyprogesterone acetate and epirubicin in the treatment of advanced breast cancer.

A phase II trial of sequential oral medroxyprogesterone acetate (MPA) and epirubicin was performed in 12 postmenopausal women with advanced breast cancer. Patients received MPA at a dose of 500 mg twice daily by mouth for 25 days. Following a 3-day washout, epirubicin was administered in a dose of 75 mg/m2. After a 3-week hiatus, the cycle was recommenced with MPA. Responses were evaluated at the end of the first 25-day period of MPA and following the end of the first cycle. Partial responses were obtained in two patients (17%)--one after the first 25 days of MPA and the other at the end of the first cycle. One of the patients had chest wall disease and the other had hepatic involvement with ascites. Minimal toxicity was experienced from this regimen and the response durations were 2 and 7 months. The response rate reported here does not warrant the further development of sequential therapy. The dose intensity of both MPA and epirubicin are compromised and may be the cause of this low response rate.

Adult↗

PubMed1984

Advanced breast cancer: response to high dose oral medroxyprogesterone acetate.

We treated 105 patients with advanced breast cancer, using the progestational agent medroxyprogesterone acetate (MPA), 200 mg orally tds in a non-randomised trial. In general they were a poor risk population, since 78 had received prior endocrine therapy (21 more than one type) and 58 prior chemotherapy. Treatment was well tolerated. Side effects included weight gain, muscle cramps, fine tremor and fluid retention, but these were usually mild, resolved if the dose of drug was reduced, and only one patient stopped treatment because of toxicity. Seventeen patients died within six weeks of starting MPA, and disease progression occurred in a further 58. Nine have had stable disease for periods ranging from two to 11 months, and there were 21 who showed disease regression. Response to treatment continues in 13 of these patients, and at the time of writing the median duration of response is 10 months. Response rates were similar in pre- and post-menopausal patients. The dose of MPA was double to 400 mg tds in 16 patients whose disease had progressed on 200 mg tds, but no additional responses were seen in this group. Seven out of 24 (29%) patients who had not received prior endocrine therapy responded to high dose oral MPA, a response rate similar to that seen following other hormonal manipulations, but because the drug also has activity against hormone-resistant tumours and is well tolerated, it should have role in the treatment of advanced breast cancer.

Antineoplastic Agents↗

PubMed1988

Lack of gonadal protection by medroxyprogesterone acetate-induced transient medical castration during chemotherapy for testicular cancer.

The serum FSH levels were analysed in 24 testicular cancer patients 3 to 9 years after intensive chemotherapy. Sperm cell counts were performed in 12 patients. In all cases a temporary medical castration had been achieved during intensive chemotherapy by the use of medroxyprogesterone acetate (MPA) (500 mg daily per os). The hormone treatment was initiated on day 1 of the first chemotherapy cycle. Thirteen additional patients did not receive this hormone treatment but were treated by similar chemotherapy. The latter patients served as a control group. There was a tendency towards higher FSH levels in the MPA-treated patients than in the controls. Following treatment, serum testosterone was significantly lower in patients who had received MPA during their intensive chemotherapy than in the controls. There was no difference between the groups with regard to recovery of sperm cell production after chemotherapy. An MPA-induced medical castration during intensive chemotherapy in testicular cancer patients is ineffective in protecting the remaining testis against treatment-induced damage to spermatogenesis, at least if hormone treatment is started simultaneously with chemotherapy.

Adult↗

PubMed1990

Effect of high-dose medroxyprogesterone acetate on plasma hormone levels and pain relief in patients with advanced prostatic cancer.

High-dose medroxyprogesterone acetate (MPA) was given orally to 7 patients with advanced prostatic cancer and severe pain due to bone metastases; 5 patients had stable and 2 had progressive disease. Pain relief was obtained in 6 patients. Two patients who reported complete relief of pain showed suppressed levels of gonadotrophins after MPA treatment. In the other patients, suppression of plasma gonadotrophin levels was observed before treatment. The plasma levels of prolactin, growth hormone and thyroid stimulating hormone were not affected by MPA. Only 1 patient showed suppression of plasma adrenocortical trophic hormone. The plasma levels of cortisol and dihydroepiandrosterone sulphate were suppressed in 6 patients, but there was no correlation between the suppression and the occurrence of pain relief. These findings suggest that the mechanism of pain relief by high-dose MPA may be very complicated.

Adrenocorticotropic Hormone↗

PubMed1990

Treatment of stage D2 prostatic cancer refractory to or relapsed following castration plus oestrogens. Comparison of aminoglutethimide plus hydrocortisone with medroxyprogesterone acetate plus hydrocortisone.

A total of 59 patients with advanced prostate cancer relapsed from or refractory to castration plus oestrogen were treated in a randomised trial comparing 1000 to 1250 mg aminoglutethimide + 40 mg hydrocortisone (AG + HC) with 500 mg medroxyprogesterone acetate + 40 mg hydrocortisone (MPA + HC). A significantly higher objective response rate and better symptomatic control was noted in patients treated with AG + HC (31%) compared with those treated with MPA + HC (3%). The median time to treatment failure was also significantly longer for patients treated with AG + HC. These findings suggest a role for AG in the treatment of advanced prostate cancer. While both second-line hormone treatment regimens resulted in significant suppression of adrenal androgen secretion, the differences in response rate could not be explained by alterations in peripheral blood hormone levels. AG in high doses may have cellular effects which require further study.

Aged↗

PubMed1991

High-dose medroxyprogesterone acetate versus estramustine in therapy-resistant prostatic cancer: a randomised study.

A series of 105 patients with metastatic prostatic cancer, having progressed on first-line hormonal treatment, were randomised to high-dose medroxyprogesterone acetate (MPA) 1000 mg i.m. daily for 15 days, followed by 1000 mg weekly (53 patients), or to estramustine 280 mg per os twice daily (52 patients). The treatment was discontinued because of side effects in 3 of 51 evaluable MPA-treated patients and in 8 of 51 evaluable estramustine-treated patients. Progression-free survival was short in both groups and no statistically significant difference between them was observed. After 1 year, 70% of the patients had died and there was no statistically significant difference between the 2 treatments in the cumulative observed survival rates. According to modified SPCG criteria, remissions lasting from 12 to 56 weeks were noted in 13 MPA-treated patients and in 4 estramustine-treated patients. This difference was statistically significant. After cross-over, 6 of 33 patients in the MPA group had a remission compared with 1 of 24 in the estramustine group. It was concluded that the response rate, considering both subjective and objective response criteria, was better with MPA and the side effects were fewer.

Aged↗

PubMed1987

Medroxyprogesterone acetate in non-metastatic gestational trophoblastic disease.

The effect of medroxyprogesterone acetate (MPA: Depo-Provera, Upjohn) as a contraceptive agent was assessed in 45 patients with non-metastatic gestational trophoblastic disease and compared with 13 patients using hormonal and 26 patients using non-hormonal methods of contraception. In the whole group of 84 patients 18 (21.4%) required chemotherapy. There was no statistically significant difference in the incidence of persistent trophoblastic disease between MPA (9/45) and the oral contraceptive group (2/13) and MPA and the non-hormonal contraceptive groups (7/26).

Adolescent↗