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PubMed2000

Prolonged endocrine responses to medroxyprogesterone in postmenopausal women with respiratory insufficiency.

OBJECTIVE: To evaluate the endocrinologic changes associated with, and possibly responsible for, prolonged ventilatory improvement after short-term medroxyprogesterone acetate (MPA) in chronic respiratory failure. METHODS: Fourteen postmenopausal women with permanent or previous episodic hypercapnic or hypoxemic respiratory failure were enrolled in a placebo-controlled, 12-week, single-mask trial including 14-day treatment periods with placebo and MPA (60 mg daily) and a 6-week follow-up. We evaluated the duration of MPA-induced alterations on serum concentrations of progesterone, estradiol, testosterone, FSH, LH, sex hormone-binding globulin (SHBG), and prolactin. Hormones were measured four times: at baseline, after 14 days with MPA, and during the washout on days 21 and 42. RESULTS: With MPA, FSH decreased 42.7% (P <.001, 95% confidence interval [CI] -54.2, -31.6), LH 62.1% (P <.01; 95% CI -81. 0, -32.6), and SHBG 58.1% (P <.001; 95% CI -63.0, -43.9). Luteinizing hormone remained decreased (-28.7%; P <.01; 95% CI -42.0, -14.2) at the 3-week washout, whereas FSH and SHBG were back to pretreatment levels. Prolactin had a borderline initial increase of 23.5% (P =.097; 95% CI -3.5, 50.5) with MPA and a significant increase at the 3-week (31.9%; P <.05; 95% CI 1.0, 62.9) and 6-week (26.4%; P <.05; 95% CI 4.4, 48.3) washouts. CONCLUSION: Medroxyprogesterone acetate 60 mg daily for 2 weeks has both immediate (FSH, LH, and SHBG), prolonged (LH), and rebound endocrinologic (prolactin) effects up to 6 weeks after treatment. The MPA-induced widespread endocrine aftereffects could explain the earlier reported prolonged ventilatory improvement.

Chronic Disease↗

PubMed2003

Medroxyprogesterone priming and response to the ram effect in Corriedale ewes during the nonbreeding season.

The "ram effect" (RE) is an inexpensive technique that allows farmers to obtain out-of-season lambs. Five hundred and ninety-six Corriedale ewes were used in three experiments to determine the effectiveness of different medroxyprogesterone (MAP) treatments associated with the ram effect during the nonbreeding season. The aim of the first experiment was to evaluate the effectiveness of short-term (6-day) MAP priming. We obtained similar results in estrus incidence and fertility after using MAP sponges for 6, 9, and 13 days. In the second experiment, we compared the effect of sponges containing 20, 40, or 60 mg of MAP used in 6-day priming. Estrous behavior and fertility were not affected by dosage. In the third experiment, 2.5mg of MAP was administered in single treatments 0, 1, 3, or 5 days before the introduction of the rams. Medroxyprogesterone administration 1, 3, or 5 days before the introduction of the rams concentrated estrus in ewes 17 to 20 days later.

Animals↗

PubMed1997

Administration of medroxyprogesterone acetate after endomyometrial resection.

STUDY OBJECTIVE: To assess the efficacy of endometrial resection for treatment of menorrhagia in women to whom no preoperative agent was given to prepare the endometrium. DESIGN: Retrospective analysis of patients' records for all endometrial resections in which medroxyprogesterone acetate was used postoperatively. SETTING: Hospital day surgery unit. PATIENTS: Seventy patients with menorrhagia. INTERVENTIONS: The women underwent transvaginal sonography, followed by hysteroscopy and endometrial biopsy. The endometrium was removed using the 27F resectoscope followed by coagulation with the rollerball. Medroxy-progesterone acetate was prescribed for 2 months after surgery. MEASUREMENTS AND MAIN RESULTS: All women achieved a reduction in menstrual flow and 50% reported amenorrhea after endometrial resection. In only two was hysterectomy necessary due to recurrence of menorrhagia. CONCLUSION: Preoperative endometrial preparation was unnecessary when endometrial resection was carried out for treatment of menorrhagia. However, the patients received medroxyprogesterone acetate postoperatively.

Adult↗

PubMed2003

Adolescents' compliance with return visits for depot medroxyprogesterone initiation.

STUDY OBJECTIVES: To determine if and when female adolescents choosing depot medroxyprogesterone would return for a second visit for initiation of the method. DESIGN/SETTING: Retrospective chart review at an adolescent clinic in an urban health department in St. Louis, MO. PARTICIPANTS: Female adolescents aged 12-19 years old, at the initial or annual family planning visit, who chose depot medroxyprogesterone (DMPA) as their contraceptive choice but were unable to get the initial injection on the day of the visit. MAIN OUTCOME MEASURE: Time to return visit. RESULTS: A total of 144 subjects were included in the analysis. 92% or 133 subjects returned for a second visit. The average time to return visit was over 3 months, or 104 days (range 1-650 days). Teens who returned in less than 1 month were more likely to receive a hormonal contraceptive method. Only 68% of all returning teens received DMPA while 7% became pregnant prior to their return. CONCLUSION: Protocols requiring a second visit for initiation of DMPA serve as a barrier to contraceptive care.

Adolescent↗

PubMed1977

Synthesis of medroxyprogesterone bromoacetate for affinity labeling.

Medroxyprogesterone bromoacetate (17alpha-hydroxy-6alpha-methyl-4-pregnene-3,20-dione 17-bromoacetate) was synthesized by reaction of 17alpha-hydroxy-6alpha-methyl-4-pregnene-3,20-dione with bromoacetic acid--trifluoroacetic anhydride followed by treatment of the intermediate with dilute ethanolic HBr. The product forms conjugates with L-cysteine, L-histidine, and L-methionine and inactivates 20beta-hydroxy steroid dehydrogenase (E.C. 1.1.1.53.) from Streptomyces hydrogenans in a time-dependent and irreversible manner. The title compound possesses a long-acting progestational effect in day 9 pregnant bilaterally ovariectomized rats. The affinity labeling analogue of the oral contraceptive medroxyprogesterone acetate is proposed for use in reproductive biological experiments.

Affinity Labels↗

PubMed2004

[Postmenopausal hormone replacement therapy and cardiovascular risk: role of conjugated equine estrogens and medroxyprogesterone acetate].

Atherosclerosis is a chronic systemic inflammatory disease of the vasculature that accounts for the majority of morbidity and mortality in women. The incidence of atherosclerosis is low in premenopausal women and increases after ovariectomy. Experimental studies demonstrate inhibitory effects of natural estrogens on the progression of atherosclerosis. In contrast, results from recent hormone replacement trials using conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women showed no effects or even an increase in cardiovascular morbidity and mortality such as thrombosis or stroke. Therefore, conjugated equine estrogens alone or in combination with medroxyprogesterone acetate should not be recommended for the prevention or treatment of cardiovascular disease. Optimizing the risk factor profile such as cessation of smoking, normalizing body weight and blood pressure, regular physical activity, and statin treatment of patients with coronary artery disease remain important treatment options.

Cardiovascular Diseases↗

PubMed2006

Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions.

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug interactions among HIV-infected women treated with depo-medroxyprogesterone acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as a control group (N=16). PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of ARV PKs before and 4 weeks after DMPA dosing. Plasma progesterone levels were measured at baseline and at 2, 4, 6, 8, 10, and 12 weeks after DMPA dosing. There were no significant changes in MPA area under the concentration curve, peak or trough concentrations, or apparent clearance in the nelfinavir, efavirenz, or nevirapine groups compared to the control group. Minor changes in nelfinavir and nevirapine drug exposure were seen after DMPA, but were not considered clinically significant. Suppression of ovulation was maintained.

Adult↗

PubMed2000

Modulation of anthracycline activity in canine mammary tumour cells in vitro by medroxyprogesterone acetate.

Failure of chemotherapy with anthracyclines as a result of drug resistance and toxicity is a major problem in the clinical management of neoplasia. The aim of the present study was to evaluate the activity of medroxyprogesterone acetate (MPA) as a chemosensitiser on anthracycline cytotoxicity. The study investigated whether such an effect could be related to an increase in lipid peroxidation, nitric oxide production, membrane fluidity and intracellular anthracycline concentration. The results showed that anthracyclines decreased nitric oxide production but increased membrane viscosity (polarisation constant) and lipid hydroperoxide formation in canine mammary tumour cells. Moreover, it was found that both drug-induced cytotoxicity and membrane viscosity increased in the presence of MPA. Conversely, lipid hydroperoxides decreased in MPA-supplemented cells. Medroxyprogesterone acetate did not show any effect on nitric oxide production. The two anthracyclines used (doxorubicin and idarubicin) showed differential intranuclear accumulation in canine mammary tumour cells, and MPA significantly modified intracellular concentration of anthracyclines.

Animals↗

PubMed2001

Effects of low-dose continuous combined conjugated estrogens and medroxyprogesterone acetate on menopausal symptoms, body weight, bone density, and metabolism in postmenopausal women.

OBJECTIVE: The purpose of this study was to determine the effects of a low dose of conjugated equine estrogens and medroxyprogesterone acetate plus calcium supplementation on bone density, metabolism, body weight, and symptoms in young postmenopausal women. STUDY DESIGN: Sixty postmenopausal women, aged 45 to 56 years, were randomized in an open-label, 2-year trial that compared treatment with low-dose continuous combined hormone replacement therapy that contained 0.3 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate plus 1000 mg of calcium per day or treatment with 1000 mg of calcium per day alone. Menopausal symptoms were evaluated for the first 12 weeks of the study; bleeding profiles, bone mineral density, bone turnover, and body weight were assessed for 24 months. RESULTS: After 24 months, we evaluated 15 subjects in the control group (with a 50% drop-out rate) and 23 patients (with a 23% drop-out rate) in the low-dose continuous combined hormone replacement therapy group. Low-dose continuous combined hormone replacement therapy was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile and minimal side effects. In comparison with basal values, bone mineral density significantly (P <.05) increased by 2.72% +/- 0.3% in the low-dose continuous combined hormone replacement therapy group and decreased by 7.9% +/- 0.8% (P <.05) in the control group after 24 months, with parallel changes in bone metabolism marker action. In the control group, body mass index significantly (P <.05) increased from baseline value with a weight gain of 3%; in the low-dose continuous combined hormone replacement therapy group, the body mass index did not change after 24 months of treatment, and the 1.3% gain in body weight was not significant. CONCLUSION: Low-dose continuous combined hormone replacement therapy can alleviate subjective symptoms and minimize body transformations that are associated with early menopause and provide an effective protection against the activation of bone turnover and osteoporosis.

Body Weight↗

PubMed2003

Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy.

OBJECTIVE: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. STUDY DESIGN: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 microg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. RESULTS: At 3 months, 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P <.029) and bleeding and/or spotting (22% vs 44%; P <.001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P =.004 and P <.001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P <.05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. CONCLUSION: The 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study.

Adult↗

PubMed1981

Inhibition of tumor growth, vascularization, and collagenolysis in the rabbit cornea by medroxyprogesterone.

Medroxyprogesterone, dexamethasone, or cortisone, locally applied in sustained release polymer to rabbit V2 carcinoma implanted in the rabbit cornea, blocked neovascularization and three-dimensional growth of the tumor. These hormones similarly prevented the vascular proliferative response to implants in the rabbit cornea of mouse B-16 melanoma and also the response to implants of polymer containing tumor extract with angiogenesis activity. The inhibitory responses were accompanied by considerable reduction in collagenolytic activity released into culture medium by explants of the two tumors and of the corneal region containing angiogenic hepatoma extract. Morphologic studies revealed extensive three-dimensional disruption of the compact laminated collagenous structure of the cornea by untreated V2 carcinoma. In the presence of hormone the tumor grew slowly as a noninvasive two-dimensional plaque limited to the narrow region of the insertion pocket in the cornea, with no obvious disturbance of structure elsewhere. Cortisone was much les effective than medroxyprogesterone or dexamethasone. Testosterone and estradiol had no effect on the three measured properties. The data suggest that local hormonal interference with neovascularization, collagenase production, and tumor growth can prevent neoplastic invasion and destruction of a dense collagenous connective tissue.

Animals↗

PubMed2006

Medroxyprogesterone acetate exacerbates glutamate excitotoxicity.

We previously demonstrated that progesterone functions as a neuroprotective agent whereas medroxyprogesterone acetate (MPA; Provera) does not. Moreover, MPA antagonized the neuroprotective and neurotrophic outcomes induced by 17beta-estradiol (E2). Towards developing effective hormone therapies for protection against neurodegeneration, we sought to determine whether formulation, chemical features or prevention versus treatment mode of exposure affected the outcome of MPA treatment in survival of primary hippocampal neurons. Results of these analyses indicated that both crystalline MPA and a pharmaceutical formulation (Depo-Provera) lacked neuroprotective efficacy, indicating that the effects were not dependent upon MPA formulation. Likewise, MPA in the prevention and treatment paradigms were equally ineffective at promoting neuronal survival, indicating that timing of MPA administration was not a factor. Further, the detrimental effects of MPA were not due to the presence of the acetate group, as medroxyprogesterone was as ineffective as MPA in promoting neuronal survival. Moreover, MPA pretreatment exacerbated neuron death induced by glutamate excitotoxicity as indicated by a 40% increase in neuron death determined by direct live/dead cell count and a commensurate increase in the number of positive cells by terminal deoxynucleotidyl transferase-mediated nick end-labeling. Collectively these results predict that the progestin formulation of hormone therapy will affect the vulnerability of the central nervous system to degenerative insults.

Animals↗

PubMed2006

A review of drospirenone for safety and tolerability and effects on endometrial safety and lipid parameters contrasted with medroxyprogesterone acetate, levonorgestrel, and micronized progesterone.

BACKGROUND: Drospirenone, a novel synthetic progestin, possesses characteristics more like natural progesterone than other synthetic progestins, such as medroxyprogesterone acetate and levonorgestrel. The antiandrogenic and antimineralocorticoid properties of drospirenone may, in the context of menopausal management, provide potential novel benefits in its effect on lipids and blood pressure while reducing the occurrence of water retention, acne vulgaris, and hirsutism. METHODS: This review compares safety and tolerability data from clinical trials of drospirenone, medroxyprogesterone acetate, levonorgestrel, and micronized progesterone. RESULTS: Results suggest that drospirenone possesses a generally well-accepted side effect profile and resembles comparator oral progestogens in conferring endometrial protection with no significant effect on weight. One study indicates that drospirenone may have a benign effect on lipid parameters, having been seen to significantly lower total cholesterol and lowdensity lipoprotein levels while maintaining high-density lipoprotein and triglyceride levels. Drospirenone also differs from the other progestogens in lowering blood pressure levels in hypertensive patients while having a mild blood pressure-lowering effect on nonhypertensive patients. CONCLUSIONS: Among pharmacological options for menopause management, drospirenone may provide certain advantages over other progestogens in its effect on risk factors for cardiovascular disease and, thus, constitutes a useful addition to the menopausal armamentarium.

Androstenes↗

PubMed2001

A randomized controlled trial of goserelin and medroxyprogesterone acetate in the treatment of pelvic congestion.

Following identification of the proportion of pelvic congestion among symptomatic patients complaining of chronic pelvic pain, and in a totally asymptomatic group of patients requesting tubal ligation, the efficiency of goserelin acetate versus medroxyprogesterone acetate was compared objectively using pelvic venogram scores, and subjectively by symptom resolution, improvement of psychological status and sexual functioning in a prospective randomized trial in 47 patients with pure pelvic congestion syndrome. Patients received either goserelin acetate (3.6 mg/month for 6 months) or medroxyprogesterone acetate (MPA; 30 mg/day for 6 months). Among patients with chronic pelvic pain, those with pure pelvic congestion were mostly parous, had the most severe pelvic signs and symptom scores, lowest rates of sexual functioning, and higher states of anxiety and depression as compared with others. At 1 year after treatment, goserelin remained superior to MPA in terms of pelvic venographic improvement as an objective measure. In alleviation of signs and symptomatology, improvement of sexual functioning and reduction of anxiety and depressive states as subjective measures, goserelin acetate achieved a statistically significant advantage (P = 0.0001) compared with MPA.

Adnexal Diseases↗

PubMed1999

Recent clinical issues related to the use of depot medroxyprogesterone acetate (Depo-Provera).

This report critically reviews recent original research articles concerning patient use of depot medroxyprogesterone acetate. Specifically, recent studies have been conducted on the following clinical issues: depression, galactorrhea, weight gain, bone mineral density, epithelial and mucus changes in the lower genital tract, and the acceptability of and continuation rates with the use of depot medroxyprogesterone acetate.

Bone Density↗

PubMed2004

A comparative pharmacokinetic study of micronized estradiol valerate administered alone and in combination with medroxyprogesterone acetate in postmenopausal women.

The objective of this study was to evaluate a possible pharmacokinetic interaction between 17beta-estradiol (E2) and medroxyprogesterone (MP) when administered together in a combined tablet because both hormones have common metabolic routes of biotransformation. The study assessed the mean pharmacokinetics parameters of E2 found after 1-dose administration of 2 different tablets containing E2, 1 containing 2 mg of micronized 17beta-estradiol valerate (E2V) and the other, administered after 2 weeks, 2 mg of E2V in combination with 5 mg of medroxyprogesterone acetate (MPA). The subjects were 15 healthy postmenopausal women with normal laboratory and clinic tests. The study was randomized, double blind, crossover, with 2 periods and 2 sequences. The blood samples were obtained at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each administration. The E2 serum concentrations were determined by electrochemoluminiscence assay. From these data, the following pharmacokinetic parameters were calculated for E2 alone and E2 in combination with MPA (E2V/MPA): Cmax = 104.89 +/- 26.96, 103.27 +/- 44.40; AUC0-24 =1900.30 +/- 392.23, 1783.70 +/- 756.39; AUC0-infinity = 5576.06 +/- 4065.87, 5317.89 +/- 3702.54; ka = 1.06 +/- 0.31, 1.09 +/- 0.13; t1/2 = 35.65 +/- 20.62, 36.12 +/- 18.04; MRT = 16.29 +/- 8.77, 16.27 +/- 4.88; V/F = 16.29 +/- 8.76, 16.27 +/- 4.88. No significant differences between the pharmacokinetic parameters of E2 and E2/MPA were found, which led us to conclude that there is no pharmacokinetic interaction.

Area Under Curve↗

PubMed2004

Urinary tract infection in the users of depot-medroxyprogesterone acetate.

BACKGROUND: The effects of progesterone on muscle tone, peristalsis of the ureter and also urinary vasculature may cause urinary tract infection (UTI) in women who use depot-medroxyprogesterone acetate (DMPA) for contraception. METHODS: In a cohort study, 200 women who chose DMPA for contraception were compared with 200 women who used the withdrawal method for urinary infection and urological symptoms after 3 months of consumption. RESULTS: The rate of urinary infection and urological symptoms in the study group were higher than in the control group (p = 0.018, p < 0.0001, respectively). The most common microorganism that caused urinary infection was Escherichia coli. Among the 10 cases who suffered UTI in the case group, there were six women who had UTI in the previous pregnancy as well. CONCLUSION: We do not recommended administering depot-medroxyprogesterone acetate for contraception in women with a history of urinary tract infection in a previous pregnancy.

Adolescent↗

PubMed1995

Phasic serum lipid excursions occur during cyclical oral conjugated oestrogens but not during transdermal oestradiol sequentially combined with oral medroxyprogesterone acetate.

BACKGROUND AND OBJECTIVE: Recent data indicate that oral medroxyprogesterone acetate (MPA) has limited unfavourable, neutral or even favourable effects on serum lipid fractions when added to oestrogen replacement therapy. The purpose of this study was to evaluate the serum lipid fractions at the beginning and at the end of each phase of a sequentially combined replacement cycle comparing the oral and the transdermal routes of oestrogen administration. DESIGN: Randomized study with a matched control group. Oral conjugated oestrogens (OCE, 0.625 mg) or transdermal oestradiol (TE 50 micrograms) was taken from day 1 to day 25 and MPA (5 mg) added on days 14 to 25. Serum lipids were evaluated on days 1, 14 and 25 of monthly replacement cycles. PATIENTS: The early post-menopausal women in the control group (n = 11) and in the treatment groups (OCE/MPA, n = 15; TE/MPA, n = 17) were evaluated every 3 months for 12 months and every 6 months for another 12 months. MEASUREMENTS: Serum levels of triglycerides (TG), cholesterol (C) fractions and apolipoproteins (Apo) and their respective ratios were measured at months 1, 3, 6, 9, 12, 18, 24. Menopausal symptoms and uterine bleedings were evaluated in parallel and an endometrial biopsy was performed at the end of the 12th and 24th months of treatment. RESULTS: After 14 days of OCE, C, LDL-C, and Apo B were decreased and TG, HDL-C and Apo A1 were increased. The sequential addition of MPA accentuated the reduction of LDL-C and Apo B but attenuated the elevation of TG, HDL-C and Apo A1. These changes tended to revert toward baseline during the period free of medication. By contrast, at the end of 14 days of TE there was a non-significant reduction in TG and LDL components and a limited increase in HDL-C and Apo A1. During the subsequent addition of MPA there was no significant decrease in TG, LDL-C or Apo B but an elimination of the increase in HDL components. These combined changes resulted in a significant reduction in the LDL-C/HDL-C ratio and a significant elevation in the Apo A1/Apo B ratio only in the OCE/MPA group. CONCLUSION: Overall, oral conjugated oestrogens induced favourable intragroup changes in cholesterol fractions whereas transdermal oestradiol maintained serum lipids at levels not different from baseline. The sequential addition of oral medroxyprogesterone acetate attenuated the beneficial elevation of HDL, did not affect the beneficial effect of oestrogens on ratios of cholesterol fractions and attenuated the unfavourable effect of oral conjugated oestrogens on triglycerides. The partial loss of beneficial effects on lipoproteins during cyclical interruption of hormone therapy would be an argument in favour of the evaluation of continuous regimens of oestrogen/progestagen replacement.

Administration, Cutaneous↗