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At least 163 records · Page 9Linked to original sources

Medroxyprogesterone acetate antiandrogen treatment of hypersexuality in a pedophiliac sex offender.

A hypersexual pedophiliac sex offender was treated with the antiandrogen medroxyprogesterone acetate for 500 days. During the treatment, his testosterone blood levels significantly decreased, nearly to female values. Pituitary gonadotropin and urinary steroid metabolite levels diminished initially. Medroxyprogesterone therapy resulted in decreased libido, few side effects, and no recurrence of sex offenses, but there was no change in the patient's sexual orientation.

Adult↗

Influence of medroxyprogesterone acetate (Provera) on plasma growth hormone levels and on carbohydrate metabolism. II. Studies in the ovariohysterectomized, oestradiol-primed bitch.

The combined effects of oestradiol and medroxyprogesterone acetate on growth hormone (GH) levels and carbohydrate metabolism were studied in 6 ovariohysterectomized dogs, which previously had shown moderate increments in GH after medroxyprogesterone acetate (MPA) administration. Oestradiol (Oe2) implants were administered 5 months after the last MPA injection, when MPA and GH levels tended to decrease. Following Oe2 administration GH levels rose significantly. Single MPA injections (100 mg) given 20 days after Oe2-priming were followed by still further increased GH levels. These GH levels were several-fold higher than GH levels achieved by previous MPA administration alone. GH levels decreased in 3 dogs after 35 days and remained elevated in the other 3 dogs as long as 70 days after MPA administration with Oe2 priming. Glucose assimilation became impaired and insulin response to a glucose load increased in relation to elevated GH levels. Oe2-primed control dogs, which received no MPA, failed to develop elevated GH levels. These findings indicate (1) that Oe2 and MPA induce overproduction in ovariohysterectomized dogs synergistically (2) that GH levels of the magnitude evoked are associated with glucose intolerance and insulin resistance.

Animals↗

Effects of long-term administration of high doses of medroxyprogesterone acetate on hormone receptors and target organs in the female rat.

The changes in oestrogen, progesterone and prolactin receptor levels in target organs, and the macroscopic and microscopic modifications of uterus, ovary, adrenal and pituitary gland induced by long-term administration of high doses of medroxyprogesterone acetate (MPA) were investigated in female rats. Medroxyprogesterone acetate was injected i.m. for 30 days at daily doses of 7.5, 15 and 75 mg/kg. Oestrogen and/or progesterone-binding capacities were remarkably reduced at all doses of MPA used both in the uterus and pituitary gland. Furthermore, MPA caused a very evident reduction in the weight of pituitary glands, ovaries, adrenals and uterus. In all MPA-treated rats corpora lutea were absent from the ovaries, whereas the adrenals showed a significant reduction in the thickness of the cortex. In accordance with this, there was no evidence of ACTH-producing cells in the pituitary glands. Prolactin-producing cells were also absent, while GH-producing cells were present. Serum prolactin levels were significantly reduced at all doses of MPA used. A dramatic reduction of prolactin receptor concentrations was observed in the liver and the ovaries of MPA-treated rats. The results suggest that MPA acts as an antioestrogenic drug both by reducing the number of oestrogen receptors in target tissues and by changing the structure (and perhaps the function) of those organs (pituitary glands, ovaries and adrenals) which are, directly or indirectly, a source of oestrogens. The decreased synthesis of prolactin and the reduction of the number of prolactin receptors (which, on the contrary, are both increased by oestrogens) might be considered as additional antioestrogenic effects of MPA.

Adrenal Glands↗

Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist plus medroxyprogesterone acetate.

Highly potent agonists of gonadotropin-releasing hormone (GnRH) have been shown to reduce pelvic pain due to endometriosis and the size and number of implants seen at laparoscopy. The accompanying symptoms and problems associated with the hypoestrogenism induced by the agonist have reduced its acceptability and raised questions about its safety. In an attempt to optimize this form of therapy, we treated eight women with endometriosis with daily subcutaneous injections of a potent agonist of GnRH plus a daily oral dose of 20-30 mg of medroxyprogesterone acetate for 24 weeks. Ovarian estrogen secretion was reduced to levels seen in castrated women throughout the course of treatment. Markers of hypoestrogenism, such as hot flashes and loss of calcium from bone, were diminished with this regimen compared with previous findings with GnRH agonist alone. Blinded evaluation of laparoscopic photographs failed to reveal improvement or suppression of active endometriosis. The results of this pilot study indicate that the addition of medroxyprogesterone acetate decreases the hypoestrogenic effects of GnRH agonist alone but fails to affect pain or endometriotic implants.

Adult↗

A randomised controlled trial of medroxyprogesterone acetate in mastalgia.

A double-blind crossover study giving 20 mg/day of medroxyprogesterone acetate during the luteal phase was carried out in 26 women with cyclical mastalgia. Symptomatic response to this progestogen supplementation or placebo was assessed objectively by clinical examination and subjectively by linear analogue scales and breast pain charts. No significant relief of pain or tenderness was found on placebo or active treatment, irrespective of treatment order, and breast nodularity was similarly unaltered. No evidence of progesterone deficiency or prolactin abnormality was found. Side-effects were incurred in 11 patients (five on placebo, five on active treatment and one while on both) and were mostly vague premenstrual symptoms. We conclude that the therapeutic response of medroxyprogesterone acetate in cyclical mastalgia is no better than placebo and that progestogen supplementation can no longer be recommended for routine use in the management of breast pain.

Adult↗

[Remarkable pain relief in the treatment with high-dose medroxyprogesterone acetate in advanced prostatic carcinoma].

A 60-year-old man was admitted to our hospital because of lumbago due to a metastatic bone tumor that originated from the prostate. Previously, he had been treated with 500 mg/kg of diethylstilbestrol diphosphate and 75 mg/day of chlormadinone acetate. At our hospital, he was given 470.1 mg/day of estramustine sodium phosphate and a bilateral orchiectomy was performed. However, he felt increased lumbago. Thus, a dose of 1200 mg/day of medroxyprogesterone acetate was started. Although the histology of his prostate and bone scintigram did not change, the patient no longer felt lumbago from about 2 weeks after the start of this treatment. Six months later, he remains free of lumbago. In this report, we describe the effect of high-dose medroxyprogesterone acetate on the clinical course, and the plasma and urine levels of the hormones.

Adrenocorticotropic Hormone↗

[Pain relief by high-dose medroxyprogesterone acetate in advanced prostatic cancer].

The effect of high-dose medroxyprogesterone acetate was studied in 7 patients with advanced prostatic cancer. Results in 7 patients were no change (NC) in 5 (71%) and progressive disease (PD) in 2 patients (29%). However, pain relief was obtained in 6 of the 7 patients (86%). As side effects, 2 patients (29%) showed moon-face and 2 patients weight gain (29%). These results indicate that treatment of high-dose medroxyprogesterone acetate is useful for pain relief in patients with advanced prostatic cancer.

Adenocarcinoma↗

Experimental local administration of CDDP to in vitro models of gynecological malignant tumors transplanted into nude mice (compared with medroxyprogesterone acetate orally administered).

In order to develop a new method of administration for CDDP, in vitro models of malignant tumors in the field of gynecology were prepared using two cell lines maintained by the authors, and fundamental experiments on the topical injection of CDDP were carried out. In experimental topical injection of CDDP in tumor-bearing nude mice, the test drug demonstrated an excellent tumor regression effect and an inhibitory effect on tumor growth. In the histopathologic examinations, specific necrosis of tumor cells was observed. It was confirmed that this is a highly safe method, as tissue separation, ulceration, or hemorrhagic lesions attributable to the local administration of CDDP were not observed. In the present study, treatment with oral medroxyprogesterone acetate was also used. At the doses used in this study, however, no inhibitory effect on tumor growth or synergism between medroxyprogesterone acetate and CDDP was observed. Topical injection is an excellent pharmacodynamic method that permits the injection of free platin into the tumor itself or in the boundary area between the tumor and normal tissues, with no loss of the drug, and it is considered a safe and effective mode of local administration. Intra-arterial injection of this drug alone or in conjunction with OK-432 can also be used, even though further studies will be required to determine the optimum dosage and reduce side effects. At present, data are being collected on terminal cancer patients for whom no other therapy is available. In the near future this method of administration is expected to be utilized in the clinical treatment of malignant tumors, be it early tumor or progressive cancer.

Administration, Oral↗

Effects of medroxyprogesterone on the liver function and drug metabolism of patients with primary biliary cirrhosis and chronic active hepatitis.

Effects of medroxyprogesterone acetate on the clinical course of six patients with primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH) were investigated. The response in all subjects was good; the subjective symptoms decreased, the liver function tests showed a tendency towards normal values. Furthermore, the levels of serum antibodies declined and the hepatic metabolic ability, as tested by serum albumin levels and indices of drug metabolism, improved. The beneficial influence of progesterone on the patients may be due to the immunosuppressive effect and enhancement of protein synthesis. The results suggest that medroxyprogesterone may be a valuable alternative for patients with autoimmune liver disease, particularly in cases developing resistance or undesirable reactions to the previous therapy.

Adult↗

Ethinyl estradiol and medroxyprogesterone acetate in patients with epithelial ovarian carcinoma: a phase II study.

Patients with ovarian carcinoma refractory to chemotherapy received a sequential combination of ethinyl estradiol and medroxyprogesterone acetate in two dose regimens. There was no difference in therapeutic activity of the two dose regimens. Of 65 patients, nine (14%) responded to treatment and 13 (20%) had stable disease. Vascular complications occurred in three patients; hemiplegia developed in one of those. Nine patients had significant nausea and vomiting, and one experienced severe depression that required treatment withdrawal. The sequential and combined use of ethinyl estradiol and medroxyprogesterone acetate may provide an alternative treatment for certain patients with ovarian carcinoma that does not respond to optimum chemotherapy. Additional studies are required to determine if synergism exists between this treatment and other modalities of therapy. Further investigation is required into the vascular disorders that complicate therapy to determine whether appropriate preventive measures are possible.

Adult↗

Modification of aflatoxin B1-induced changes in certain mitochondrial enzymes and lipids by medroxyprogesterone acetate.

The effect of a single dose of 5 mg/kg body weight of aflatoxin B1 on rat liver mitochondrial enzymes, succinate dehydrogenase (SDH) and Mg++ adenosine triphosphatase (Mg++-ATPase) and on certain lipids were studies at various intervals of time from 3 to 24 hours. A significant decrease in the specific activity of SDH was observed after 6, 12, 18 and 24 hr treatment. The Mg++-ATPase activity remained unaffected up to 12 hr but appreciably decreased after, 18 and 24 hr of the treatment. The level of phospholipids and cholesterol were not altered after 3, 6 and 12 hr treatment, thereafter (18 and 24 hr) an increase was observed in both the lipids following the aflatoxin treatment. Medroxyprogesterone acetate (MPA) did not cause any alteration in the specific activities of these enzymes as well as levels of cholesterol and phospholipids. The treatment with MPA caused significant increase in contents of cytochromes P-450, b5 and activities of Arylhydrocarbon hydroxylase (AHH), UDP-glucuronyl transferase (UDP-GT) and NADPH-cytochrome C-reductase of hepatic microsomes. It was observed that pretreatment with medroxyprogesterone acetate (MPA) could significantly minimuze the depression caused in mitochondrial SDH and Mg++-ATPase activities by aflatoxin B1.

Aflatoxin B1↗

High-dose oral medroxyprogesterone acetate in heavily pretreated patients with metastatic breast cancer.

Fifty heavily pretreated postmenopausal patients with advanced breast cancer were treated with oral medroxyprogesterone acetate (1 g) daily for 1-18 months. Eight patients (16%) responded to treatment for periods up to 18 months and in an additional eight patients (16%) the disease stabilized for up to 10 months. Thirty-two patients (64%) developed adverse effects and eight (16%), all of whom had extensive pulmonary metastases, died a respiratory-related death thought possibly to have been brought on or accelerated by treatment. Only eight patients (16%) experienced increased appetite, weight gain, feeling of wellbeing, or improved performance status. We conclude that medroxyprogesterone acetate is useful in patients with advanced metastatic disease but should be restricted to carefully selected patients and used only with extreme caution in patients with underlying cardiovascular or respiratory disease. Its major application probably lies in the benefit it confers earlier in the disease.

Adult↗

Medroxyprogesterone acetate at very high doses in postmenopausal advanced breast cancer patients.

Twenty-six postmenopausal consecutive patients with advanced breast cancer were treated with very high medroxyprogesterone acetate doses (4000 mg/day orally for 30 days and then 3000 mg/day orally until progression or intolerance). The dominant metastatic lesion was bone in 13 patients, soft tissue in 3 patients and viscera in 10 patients (C.I. = V/ST + 0 = 0.62). An objective partial remission was achieved in 16 pts (61%), no change in 8 (31%), progression in 2 (8%). The median duration of objective remission was 7.5+ months with a median survival of 14.5+ months in responders. Toxicity was minor and only two patients discontinued the treatment because of side-effects. These results confirm the utility of medroxyprogesterone acetate at very high doses in these patients and the feasibility of this kind of dose.

Adult↗

Effect of progesterone and medroxyprogesterone acetate on pregnancy length and litter size in mink.

The objective of these studies was to determine the effect of progesterone and medroxyprogesterone injected at varying times post coitum on gestation length and litter size. During a 3-year period mink females of "Standard" strain were given progesterone at a dose 5 mg at 15 and 20 days in the first year and at 17-20 days in the second year, after the last mating. The respective control groups were given the vehicle. Medroxyprogesterone acetate was given in the second year at a dose of 4 mg at 14-19 days following the last mating and in the third year at a dose of 2 mg at 8 days after the last mating. The results on pregnancy length and litter size after progesterone injections in the experimental and respective control groups were as follows: 52.7 days and 4.3 kits, 51.3 days and 4.3 kits, 52.2 days and 5.8 kits, 50.2 days and 4.8 kits, 44.7 days and 5.6 kits, 46.0 days and 6.1 kits. A dose of 4 mg MPA resulted in the blockage of parturition in pregnant females. After administration of MPA at doses of 2 mg at 8 days following the last mating, the pregnancy length and litter size in the experimental group were: 48.0 days and 6.1 kits and in the control: 52.2 days and 4.8 kits.

Animals↗

[Diverse action of 17-alpha-hydroxyprogesterone caproate and medroxyprogesterone acetate on the biosynthesis of collagen and cirrhogenous course of CC14-induced hepatic lesions in rats].

The administration of medroxyprogesterone acetate to rats did not induce rapidly progressing cirrhosis in livers damage by carbon tetrachloride, as had occurred after the administration of 17-alpha-hydroxyprogesterone caprate. Even after two months' treatment with medroxyprogesterone acetate and CC14, the cirrhosis did not reach the levels obtained in a single month with the association of 17-alpha-hydroxyprogesterone and CC14.

17 alpha-Hydroxyprogesterone Caproate↗

Ovarian function following a single administration of depo-medroxyprogesterone acetate (DMPA) at different doses.

The effects of a single administration of depo-medroxyprogesterone acetate (DMPA) at different doses upon ovarian function was studied in a group of healthy ovulating Mexican women. Single doses of DMPA of 25, 50, 100, and 150 mg were intramuscularly administered. Ovarian function was assessed by the measurement of the serum levels of 17 beta-estradiol and progesterone in blood samples drawn twice weekly for 6 months after DMPA administration. The results disclosed that ovulation was inhibited in all cases for at least 3 months following DMPA administration even at the lowest dose, whereas the return of luteal function exhibited a significant positive correlation with the dose of DMPA administered. As expected, follicular activity preceded that of luteal function in all subjects. A correspondence between serum medroxyprogesterone concentrations and ovarian function was found. The overall data indicated that the currently used contraceptive formulation (150 mg) is well above the effective pharmacologic range, and suggested that the dose can be substantially reduced without losing its anovulatory potency.

Adolescent↗

Cholelithiasis induced in the Syrian hamster: evidence for an intramucinous nucleating process and down regulation of cholesterol 7 alpha-hydroxylase (CYP7) gene by medroxyprogesterone.

This report reviews previously published studies from our laboratory and shows some recent morphological data obtained with scanning and transmission electron microscopy regarding gallstone formation and alteration of the gallbladder epithelium in the Syrian hamster model. Both male and female hamsters were treated with female sex steroids (estradiol alone, estradiol and medroxyprogesterone, medroxyprogesterone alone) during one month. The results show that the Syrian hamster is a good model to study bile changes, gallbladder structure changes, including gallstone formation, and the regulation of cholesterol metabolism at the molecular level. Arguments in favor of this animal model are presented and, during gallstone formation, epithelial cell changes, anionic mucus secretion, and formation of gallbladder luminal deposits can be demonstrated. Recent molecular biology observations related to the effect of female sex steroids on liver cholesterol 7 alpha-hydroxylase (CYP7) gene suggest that progestin alone or primed by estrogen down regulates CYP7 transcription and activity. In addition, progesterone in cell culture systems has been shown to enhance intracellular accumulation of free cholesterol by increasing its uptake and synthesis and by decreasing its esterification by inhibiting the activity of acylcoenzyme A: cholesterol acyltransferase. Non-esterified cholesterol is free to migrate to the extracellular spaces and may contribute to nucleation within the bile. It is suggested that these effects of progesterone on cholesterol metabolism combined with the CYP7 gene down regulation, physical changes in the mucus and the hypomotility of the gallbladder and biliary ducts result in hypersaturation of cholesterol in the bile which favors gallstone formation.

Acyl Coenzyme A↗

Fatal pulmonary toxicity by the association of radiotherapy and medroxyprogesterone acetate.

This report describes a fatal pneumonitis occurring in a breast cancer patient while on adjuvant treatment with radiotherapy and medroxyprogesterone acetate. The clinical and radiologic features, as well as the timing of this pneumonitis, make a radiation pneumonitis more than probable. A radiation pneumonitis was also observed in other patients treated in the same way. Medroxyprogesterone acetate thus seems to act as a radiosensitizer since no such effects were seen in patients treated with radiotherapy alone. The radioenhancing effect is not limited to the lungs, since radioesofagitis was also encountered in similarly treated patients.

Aged↗