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Results for “Medroxyprogesterone Acetate”

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PubMed1976

The in vivo metabolism of progestins. I. The metabolic clearance rates of progesterone and medroxyprogesterone acetate in the dog.

[3H]Medroxyprogesterone acetate (MPA) was synthesized by selective catalytic tritiation of the delta1-olefinic bond of 6alpha-methyl-17alpha-hydroxy-pregn-1,4-diene-3,20 dione acetate. [14C]MPA was synthesized by acetylation of 6alpha-methyl-17alpha-hydroxy-pregn-4-ene-3,20-dione with [14C]acetic anhydride. These radioactive materials were used to determine the MPA metabolic clearance rates (MCRMPA)and volumes of distribution (VoMPA) in dogs by the single injection technique. The metabolism of progesterone was also studied in the same animals. The MCRMPA (696 +/- 51 l/day) was only one-half that of progesterone (1332 +/- 59). By contrast, the volumes of distribution for the two steroids were similar. The metabolic clearance rates and the volumes of distribution for MPA and progesterone did not change during treatment with amino-glutethimide, a drug which is known to alter steroid metabolism in man.

Aminoglutethimide↗

PubMed1996

Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis.

OBJECTIVE: Our purpose was to evaluate the efficacy and safety of depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol in the long-term treatment of pelvic pain in women with endometriosis. STUDY DESIGN: Eighty patients with endometriosis and moderate or severe pelvic pain were randomized to treatment for 1 year with intramuscular depot medroxyprogesterone acetate 150 mg every 3 months or a cyclic monophasic oral contraceptive (ethinyl estradiol 0.02 mg, desogestrel 0.15 mg) combined with oral danazol 50 mg a day for 21 days of each 28-day cycle. The women were asked to grade the degree of their satisfaction at the end of therapy. Variations in severity of symptoms during treatment were determined by a 10 cm visual analog and a 0- to 3-point verbal rating scale. RESULTS: Twenty nine of 40 subjects (72.5%) in the depot medroxyprogesterone acetate group were satisfied after 1 year of therapy compared with 23 of 40 (57.5%) in the oral contraceptive plus danazol group (chi 2(1) = 1.37, p = 0.24, odds ratio 1.95, 95% confidence interval 0.76 to 4.97). A significant decrease was observed in all symptom scores in both study groups. At 1-year assessment dysmenorrhea was significantly greater in women allocated to oral contraceptive plus danazol. CONCLUSION: Depot medroxyprogesterone acetate seems to be an effective, safe, and convenient low-cost treatment for pelvic pain associated with endometriosis. However, women should be carefully counseled regarding menstrual changes and the potential prolonged delay in the return of ovulation.

Adolescent↗

PubMed1995

[Clinical trial of high-dose medroxyprogesterone acetate in advanced breast cancer].

Sixty-two evaluable patients with advanced breast cancer were treated with medroxyprogesterone acetate (Farlutal. Erba) 500mg orally twice or three times a day. After thirty days, one patient had a complete response (1.6%), 33 patients had partial response (53.2%). 11 had stable disease (17.7%), and 17 progressive disease (27.4%). The response rates of bone, lung and chest wall metastasis were higher. And the older patients showed a better response than the younger. The response did not show significant correlation with KPS, menopausal status, disease-free intervals after operation, numbers of metastases and the dose of medroxyprogesterone acetate. The response rate in ER positive patients was higher than the ER negative, but the difference was not statistically different. The side effects of high-dose medroxyprogesterone acetate were well tolerated and the most common ones were weight gain and excessive perspiration.

Adult↗

PubMed1997

Cellular changes in prostatic carcinoma after treatment with orchidectomy, estramustine phosphate and medroxyprogesterone acetate.

Thirty-three patients with prostatic carcinoma were treated with either estramustine phosphate, orchidectomy or high dose medroxyprogesterone acetate. Therapy response was evaluated by cytological examination of fine needle aspiration biopsies performed before and after 6 weeks treatment. At follow-up, 11 of 14 patients treated with estramustine phosphate had regressive and/or degenerative changes, in 2 patients there were no prostatic carcinoma cells in the smears and in one there was a marked reduction of the number of tumour cells. In 7 of 10 patients treated with orchidectomy there was a marked reduction of the percentage of malignant cells while smears from 3 patients were unchanged. In the 8 patients treated with high dose medroxyprogesterone acetate the cell patterns were unmodified compared with before treatment. We conclude that, in contrast to the lack of effect of treatment with medroxyprogesterone acetate, treatment with orchidectomy and especially estramustine phosphate caused morphologic cellular changes in prostatic carcinoma.

Aged↗

PubMed2001

Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17beta-estradiol and norethindrone acetate.

OBJECTIVE: We studied bleeding patterns in postmenopausal women who were using 2 types of continuous combination regimens. STUDY DESIGN: A prospective, double-blind, randomized study of 208 postmenopausal women treated with conjugated estrogen, 0.625 mg, and medroxyprogesterone acetate, 5 mg, or with 17beta-estradiol, 2 mg, and norethindrone acetate, 1 mg. RESULTS: The mean number of bleeding days decreased during the first 4 months of treatment (P <.002) but not thereafter. The number of bleeding days was fewer (P <.002) and the time until amenorrhea was shorter (P <.02) in patients receiving conjugated estrogen and medroxyprogesterone acetate than in patients receiving 17beta-estradiol and norethindrone acetate. The odds ratio for progression to amenorrhea with the use of conjugated estrogen and medroxyprogesterone acetate was 1.58, in comparison with the use of 17beta-estradiol and norethindrone acetate. A thick endometrium at the start of treatment resulted in more bleeding days than were found for a thin endometrium (P <.03). Body mass index, age, and blood pressure had no predictive value for bleeding problems. CONCLUSIONS: Treatment with continuous combined conjugated estrogen and medroxyprogesterone acetate resulted in fewer bleeding problems than did treatment with 17beta-estradiol and norethindrone acetate. Endometrial thickness may help to predict the chance of achieving amenorrhea during early hormone replacement therapy.

Aging↗

PubMed1989

[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↗

PubMedDate not supplied

Results of a dose-intense phase 1 study of a combination chemotherapy regimen with cisplatin and epidoxorubicin including medroxyprogesterone acetate and recombinant interleukin-2 in patients with inoperable primary lung cancer.

Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.

Adult↗

PubMed1992

Direct effects of medroxyprogesterone acetate, danazol, and leuprolide acetate on endometrial stromal cell proliferation in vitro.

OBJECTIVE: To assess the direct effects of three endometriosis chemotherapeutic agents (medroxyprogesterone acetate [MPA], danazol, and leuprolide acetate [LA]) on endometrial cell proliferation. DESIGN: Analysis of cell proliferation in vitro. SETTING: Proliferative phase endometrial stromal cells isolated from biopsy specimens and grown in short-term culture served as a model for stromal components of endometriotic implants. PATIENTS: Biopsies obtained from volunteers with regular cycles and without endometriosis or endometrial pathology. INTERVENTIONS: Medroxyprogesterone acetate, danazol, and LA were added to nutrient media with the following supplements: 2.5% calf serum (CS) only; 2.5% CS+estradiol (E2) 110 pmol/L; 2.5% CS+E2 550 pmol/L; 10% preovulatory serum (net E2 624 pmol/L). MAIN OUTCOME MEASURES: Cumulative [3H]-thymidine incorporation as a reflection of cell proliferation. RESULTS: Medroxyprogesterone acetate and danazol exerted significant antiproliferative effects on stromal cell proliferation (P less than 0.05), effects that were enhanced by an absence of exogenous E2. Leuprolide acetate exerted no consistent effects. CONCLUSIONS: These data imply that MPA and danazol but not LA exert direct effects, suppressing growth of endometriotic implants.

Adult↗

PubMed1998

The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women.

OBJECTIVE: Depot medroxyprogesterone acetate (DMPA), an injectable progestogen, is a widely used contraceptive acting primarily by inhibiting secretion of pituitary gonadotrophins, thus producing oestrogen deficiency. Cross-sectional and prospective studies in pre-menopausal women have shown DMPA use to be associated with reduced bone density, but bone density increases following discontinuation of the drug. Because fracture rates are low in pre-menopausal women, the principal concern arising from the effects of DMPA on bone is that there may be residual osteopenia in former users such that their post-menopausal fracture risk is increased. The present study addresses this question. DESIGN: Cross-sectional study of bone density in post-menopausal former users of DPMA and controls. SUBJECTS: Three hundred and forty-six normal post-menopausal women, of whom 34 had previously used DMPA. The median age at which DMPA use began was 41 years and the median duration of use was 3.0 years. MEASUREMENTS: Bone density was measured in the spine, proximal femur and total body by dual-energy, X-ray absorptiometry. RESULTS: There were no significant differences in bone density at any site between the women who had previously used DMPA and the others in the cohort. However, in those who had used DMPA for > 2 years there was a trend towards bone densities being lower in the former users, the differences from non-users being 1.6% in the lumbar spine (P = 0.6), 3.1% in the femoral neck (P = 0.4) and 0.5% in the total body (P = 0.8). There was no correlation between bone densities and the duration of DMPA use, the age at discontinuation of DMPA, or the time between DMPA discontinuation and the menopause. CONCLUSIONS: Any residual effects of depot medroxyprogesterone acetate use on post-menopausal bone density are small and therefore unlikely to have a substantial impact on fracture risk in the post-menopausal years.

Bone Density↗

PubMed1992

Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer.

OBJECTIVE: The purpose of this study was to investigate the effect of medroxyprogesterone acetate on angiogenesis induced by endometrial cancer and to elucidate the possible mechanisms by which it inhibits the growth of the cancer. STUDY DESIGN: Tumors were obtained from 29 patients with endometrial adenocarcinoma, and angiogenesis was assayed in corneas of white rabbits. RESULTS: Transplantation of tumor tissues into rabbit corneas induced angiogenesis in 70.4% of the corneas, but their transplantation with a pellet of medroxyprogesterone acetate induced angiogenesis in only 21.5% of the corneas. This compound also inhibited angiogenesis induced by acidic fibroblast growth factor and transforming growth factor-alpha. CONCLUSION: Inhibition of angiogenesis may be one mechanism by which medroxyprogesterone acetate inhibits the growth of endometrial adenocarcinoma, and its inhibition of neovascularization induced by adenocarcinoma may be through its direct action on endothelial cells.

Adenocarcinoma↗

PubMed1990

The effect of low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test.

The effect of a low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test was studied in 29, 30 and 9 indigenous Kenyan women respectively. Glucose tolerance test was performed before treatment was started and then after 1,3 and 6 months in microgynon users. The mean areas under the glucose curves were also significantly elevated. Significant increase in blood glucose values were noted only at 30 minutes after 6 months of use of the progestogen-only oral contraceptive but the mean blood glucose values were higher than in the control after 1,3 and 6 months of use. However, the mean values of the areas under the glucose curves were significantly elevated after 1,3, and 6 months of use. Medroxyprogesterone acetate users showed significantly lower fasting blood glucose values at 60 and 90 minutes after 1 month of use, after which the blood glucose values returned to the pre-treatment values. The mean values of the glucose curve areas showed no significant change. It is concluded that both microgynon and minipill cause relative impairment of glucose tolerance test as early as after 1 month of use. Medroxyprogesterone acetate does not impair oral glucose tolerance for at least the first 6 months of use. The implications of these findings are discussed.

Adult↗

PubMed1991

Long-term effects of depot-medroxyprogesterone acetate on lipoprotein metabolism.

To assess the effects of depot-medroxyprogesterone acetate (DMPA) upon serum lipids and lipoproteins, a comparative study in chronic users and new acceptors was undertaken. Two groups of women of reproductive age were included in the study; group I (n = 8) was formed by new acceptors whereas, group II (n = 14) constituted DMPA users of more than five continuous years (7.0 + 2.1 years). Blood samples were taken on the day of injection and 15, 29, 57 and 92 days after the i.m. administration of 150 mg of DMPA for the measurement of total triglycerides (TG), cholesterol (CHOL) and phospholipids (PHL). In addition, the TG and CHOL content in the very low density (VLDL), low density (LDL) and high density (HDL) lipoprotein fractions obtained by ultracentrifugation were also determined. The results demonstrated a moderate increase in the serum total TG concentrations at the expense of the VLDL fraction in the group of chronic DMPA users. In both groups, the administration of DMPA induced a moderate, though not significant, decrease in total CHOL and HDL-chol, an effect that was noticed at the end of the treatment interval; the serum LDL-chol content remained unchanged. In addition, a decrease in the total serum phospholipids content was noticed after DMPA injection in both groups, which resembled the fluctuations observed in the luteal phase of normal ovulating women. The overall data indicate that acute and/or chronic DMPA administration at the dose currently employed for contraception does not induce major abnormalities in lipoproteins in serum.

Adult↗

PubMed1980

A study of the mechanism of weight gain in medroxyprogesterone acetate users.

Twelve non-lactating Thai women using the injectable contraceptive medroxyprogesterone acetate (DMPA) were studied in order to elucidate the mechanism of weight gain frequently seen among DMPA users. The study design included repeated estimations of body fluid compartments (total, extracellular and intravascular) and of nitrogen metabolism, as well as anthropometric measurements. The mean weight remained constant in this group of women after one year of treatment. But 25% of them demonstrated a mean weight gain of 6.05 kilograms, while another 25% showed a mean weight loss of 3.50 kilograms. None of the subjects (including those who gained and lost weight) showed significant changes in her fluid compartmental size, creatinine excretion rate, or nitrogen metabolism. However, skin-fold thicknesses were positively correlated to body weight changes. It can be concluded that medroxyprogesterone acetate when used as injectable contraceptive does not appear to have significant anabolic or fluid retaining properties, and that weight gain appears to be associated mainly with fat deposition.

Adolescent↗

PubMed1991

A randomized, double-blind, placebo-controlled, cross-over trial to assess the side effects of medroxyprogesterone acetate in hormone replacement therapy.

Cyclic progestin therapy has been widely advocated as an adjunct to postmenopausal estrogen replacement therapy to reduce the risk of endometrial carcinoma. Acceptance of this approach, however, appears to have preceded detailed evaluation of possible adverse side effects of progestins that could result in patient noncompliance. We evaluated the nonmenstrual physical and psychological side effects of oral medroxyprogesterone acetate given in conjunction with transdermal estrogen in two groups of women with previous hysterectomy and oophorectomy. Twenty-four women with prospectively documented severe premenstrual syndrome (PMS) before surgery and 24 women with no such history of adverse premenstrual changes received transdermal estrogen 100 micrograms on days 1-25 and either oral medroxyprogesterone acetate 10 mg daily or an identical placebo (days 12-25) in a randomized, double-blind, cross-over design. Mood and physical symptoms were monitored prospectively, using daily self-ratings on the Daily Symptoms Checklist. The Beck Depression Inventory and Premenstrual Tension Self-Rating Scale were completed on day 24. At the study's completion, the patients were asked which treatment period they preferred. Paired comparisons did not reveal any significant differences, and preference for treatment was equally divided between medroxyprogesterone acetate and placebo. We conclude that addition of medroxyprogesterone acetate 10 mg/day for 14 days to cyclic transdermal estrogen therapy (days 1-25) produces no consistent adverse physical or psychological effects on women for one cycle of treatment, regardless of their PMS history.

Double-Blind Method↗

PubMed2005

Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception.

OBJECTIVE: The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception. STUDY DESIGN: One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment. RESULTS: Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus -1.8% in the placebo group ( P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus -5.1% in the placebo group ( P <.001). CONCLUSION: Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.

Absorptiometry, Photon↗

PubMed1998

A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia.

A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group.

Clinical Trial↗

PubMed1998

Cytologic changes in cervical smears associated with prolonged use of depot-medroxyprogesterone acetate.

BACKGROUND: Hormonal effects have always played a significant role in gynecologic cytology. In atrophic and postpartum smears, interpretation may be complicated by large numbers of parabasal cells with high nuclear cytoplasmic ratios and hyperchromatic nuclei that mimic precancerous lesions (squamous intraepithelial lesions, SILs). The authors have observed atrophic and postpartumlike changes in patients receiving depot-medroxyprogesterone acetate for prolonged periods. These alterations may lead to diagnostic uncertainty or falsely suggest the presence of SIL. METHODS: To evaluate the effect of chronic hormone use, smears from 29 depot-medroxyprogesterone acetate users (average age, 35.9 years) who had been amenorrheic for 5-72 months (average, 22.6 months) were identified. This group was matched with 25 nonusers (average age, 31.9 years). Maturation values (MVs) were calculated for both groups and cellular findings were evaluated. RESULTS: The user group had a significantly lower MV (38.45 vs. 64.60, P < 0.001). Among users, 6 of 29 smears (21%) were abnormal. One low grade SIL was biopsy-confirmed, but two high grade SILs and three smears of ASCUS had a negative Papanicolaou (Pap) smear and/or biopsy follow-up. Among nonusers, 4 of 25 smears (16%) were abnormal. Two patients with high grade SIL smears had positive biopsy or Pap smear follow-up, one with an ASCUS smear had a negative Pap smear follow-up, and one with a low grade SIL was lost to follow-up. CONCLUSIONS: The immature cellular pattern seen in smears from long term depot-medroxyprogesterone acetate users led to difficulty in determining the diagnosis in some cases. ASCUS cases among users were associated with high nuclear cytoplasmic ratios and hyperchromasia in parabasal metaplasialike cells. Biopsies in these cases showed epithelial atrophy, which was often associated with acute inflammation. In view of the fact that long term depot-medroxyprogesterone acetate administration may induce changes that mimic high grade SIL in a population already at high risk for SIL, there may be problematic cases in which diagnostic uncertainty is inevitable.

Adult↗

PubMed1990

Comparison of mass spectrometry and radioimmunoassay to measure medroxyprogesterone acetate in patients with endometrial cancer.

Serum medroxyprogesterone acetate (MPA) was measured by radioimmunoassay (RIA) and gas chromatography-mass spectrometry (GC-MS) in patients with endometrial cancer. Samples were obtained 3, 6 and 24 h after the oral administration of 100 or 200 mg MPA once a day. The levels obtained by GC-MS were lower (median 16-29%) than those obtained by RIA, which is probably attributable to the presence of metabolites interfering with the RIA. Two commercial MPA formulations gave different MPA serum levels by both RIA and GC-MS. The levels obtained by GC-MS were so low that frequently only partial saturation of the endometrial progesterone receptor may be achieved which may explain why high oral doses are needed to produce optimum therapeutic response.

Aged↗