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PubMed1996

[Effectiveness of combination hormonal therapies in advanced or recurrent breast cancer--a randomized trial of tamoxifen (TAM), medroxyprogesterone acetate (MPA), their simultaneous combination, and an alternating sequential combination of TAM plus MPA].

The effects of tamoxifen (TAM), medroxyprogesterone acetate (MPA), their simultaneous combination or an alternating sequential combination of TAM plus MPA (TAM-MPA), was evaluated in 52 patients with advanced or recurrent breast cancer in a randomized controlled trial. The response rates of TAM, MPA, TAM & MPA, and TAM-MPA were 13.3%, 36.4%, 7.1% and 25.0%, respectively. All four therapies showed a higher response rate in the patients with soft tissues or with no previous therapy. However, there were no significant differences between the patient's characteristics and response rate among these four therapies. The differences in the frequency of adverse effects among these therapies were not significant, and there were no severe adverse effects with any therapy. In the cross-over trial of TAM and MPA, although 15.4% of patients who failed to show a response to TAM showed an objective response to MPA, no response to TAM was seen in the patients who had failed to show a response to MPA. In conclusion, TAM & MPA was not more effective than TAM or MPA, and TAM-MPA was not more effective than MPA. Adverse effects were not increased with TAM & MPA or TAM-MPA. MPA was useful as a second-line therapy after TAM.

Aged↗
PubMed1996

Effects on haemostasis of hormone replacement therapy with transdermal estradiol and oral sequential medroxyprogesterone acetate: a 1-year, double-blind, placebo-controlled study. The Writing Group for the Estradiol Clotting Factors Study.

After menopause the haemostatic balance shifts towards a latent hypercoagulable state. To evaluate the effects of two regimens of transdermal estradiol (E2) combined with progestin on the balance between procoagulant factors and inhibitors, 255 women in physiological menopause for 1-5 years were randomly allocated to 1 year of treatment with cyclic transdermal E2 (50 micrograms/day for 21 days) plus medroxyprogesterone acetate (MPA) (10 mg/day from days 10 to 21), continuous transdermal E2 (50 micrograms/day for 28 days) plus MPA (10 mg/day from days 14 to 25), or placebo. Fibrinogen, factor VII (FVII), factor VIII:C (FVIII:C), antithrombin III (ATIII), protein C, protein S, heparin cofactor II (HCII) and plasminogen activator inhibitor (PAI-1) levels were measured at baseline and after 6 and 12 cycles. 167 women who took the treatment for at least 6 cycles were evaluable. The continuous treatment group had significantly lower final values of fibrinogen, FVII, ATIII, protein S and HCII than the placebo group; the cyclic treatment reduced fibrinogen in comparison with placebo but the difference was not significant. In conclusion, both regimens produce a clinically relevant decrease of fibrinogen levels; the continuous regimen affects also the levels of FVII and inhibitors suggesting that the haemostatic balance is shifted to a more physiological state.

Administration, Cutaneous↗
PubMed1996

Depot medroxyprogesterone acetate contraception in women with medical problems.

Since few clinical trials of contraceptive agents are conducted on women with medical problems, use of these agents in these populations is often based more upon theoretical considerations than clinical data. Clinicians must distinguish the risk of estrogen in the combined oral contraceptive from the risk of the progestin-only contraceptive methods. This review compares the risks of pregnancy with the risks of contraceptive methods for patients with chronic hypertension, cardiac disease, thrombotic disorders, diabetes, epilepsy, lupus erythematosus and other medical disorders. For women with certain medical problems, estrogen, but not progestogen, may be contraindicated. For these women, a long-acting progestogen, such as depot medroxyprogesterone acetate (DMPA), may offer distinct advantages.

Cardiovascular Diseases↗
PubMed1996

Depot medroxyprogesterone acetate contraception and the risk of breast and gynecologic cancer.

As the use of depot medroxyprogesterone acetate (DMPA) contraception increases in the United States and worldwide, assessing any impact on the risk of breast and gynecologic cancers becomes increasingly important. Overall, use of DMPA does not affect breast cancer risk. An elevated risk of this disease, however, has been noted in recent or current users. Hence, the association between DMPA use and breast cancer risk appears similar to that observed with oral contraceptives. Use of DMPA is associated with an 80% risk reduction of endometrial adenocarcinoma, a level of protection even greater than that noted with oral contraceptives. The risk of epithelial ovarian cancer and cervical neoplasia does not appear to be affected by DMPA use. Except for a substantial reduction in the risk of endometrial adenocarcinoma, use of DMPA does not appear to influence reproductive tract cancer risks.

Breast Neoplasms↗
PubMed1996

Noncontraceptive benefits and therapeutic uses of depot medroxyprogesterone acetate.

This paper reviews the noncontraceptive benefits and therapeutic uses of depot medroxyprogesterone acetate (DMPA). Relevant articles were reviewed using a computerized Medline search of the literature from 1966 to 1995. Good evidence shows that DMPA use is associated with reduced iron-deficiency anemia, protection against pelvic inflammatory disease, protection from endometrial cancer and improved hematologic parameters among users with sickle cell disease. More studies are needed to fully assess DMPA's impact on other disorders.

Anemia, Iron-Deficiency↗
PubMed1995

[Pulmonary lymphangiomyomatosis: a 3-year follow-up of medroxyprogesterone acetate therapy. Apropos of a case].

A 41-year-old female patient presenting with chylothorax was found to have pulmonary lymphangiomyomatosis. Recurrence led to parietal pleurectomy. Lung biopsy performed at surgery confirmed the histology diagnosis. Hormone treatment with medroxyprogesterone acetate was initiated immediately and administered via intramuscular injections each month. The treatment was continued for three years and regular clinical, functional and radiologic follow-up provided evidence of response: radiologic and functional stability were achieved at the cost of major secondary effects of hormone therapy. This rare, apparently hormone-dependent, disease raises the problem of the long-term benefit of treatment.

Adult↗
PubMed1996

[Administration method and recurrence-preventing effect of medroxyprogesterone acetate (MPA) as a postoperative adjuvant endocrine therapy for stage III breast cancer. Kitakyushu Collaborative Study Group for Breast Cancer].

By a collaborative study undertaken by 11 medical institutions in the Kita-Kyushu area, we evaluated the clinical efficacy of the combination of medroxyprogesterone acetate (MPA) and Tamoxifen (TAM) as a postoperative adjuvant endocrine therapy for Stage III breast cancer. First, 1 course of CAF therapy was administered; then, in combination with the basic therapy of 5-FU 200 mg/day p. o. for 3 years, ER (+) patients were treated with either 2-week sequential therapy of TAM (30 mg/day) and MPA (800 mg/day) or TAM (30 mg/day), and ER (-) patients received either MPA (800 mg/day) or 5-FU alone. Neither survival nor disease-free rates of the 92 analyzable patients were different between these treatment groups. Furthermore, the blood levels of MPA and cortisol had no correlation with survival and disease-free periods. We studied the effect of MPA on the natural inhibitors of blood coagulation, but found no difference from the result in healthy adults. It was, however, shown that MPA had a bone marrow-protecting effect.

Adult↗
PubMed1977

Combination chemotherapy of advanced endometrial adenocarcinoma with adriamycin, cyclophosphamide, 5-fluorouracil, and medroxyprogesterone acetate.

Seven patients with advanced endometrial adenocarcinoma achieved objective tumor regression following chemotherapy with cyclophosphamide, Adriamycin, 5-fluorouracil, and medroxyprogesterone acetate. Combination chemotherapy has a favorable risk/benefit ratio for patients with advanced endometrial adenocarcinoma, including patients with severe debilitation, if supportive care such as hospitalization, parenteral antibiotics, and platelet transfusions are available. New Adriamycin-based drug combinations have sufficient antitumor activity to warrant major prospective evaluation by oncology cooperative groups.

Adenocarcinoma↗
PubMedDate not supplied

Effects of estrone with or without medroxyprogesterone acetate on the femur in aged rats.

In an attempt to define the efficacy of hormone replacement therapy in postmenopausal osteoporosis, we investigated the effects of estrone with or without medroxyprogesterone acetate on the bone mineral density of the femur of aged rats, of which plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol were markedly reduced in comparison with those of younger rats. Although additional sex hormones had little effect on the plasma levels of gonadotropins, chronic administration of estrone significantly enhanced the bone mineral density of femur in aged animals.

Aging↗
PubMed1996

Medroxyprogesterone and paraphiles: do testosterone levels matter?

We examine the associations between pretreatment testosterone (TTS) levels and sociodemographic, clinical, and sexual behavioral characteristics. Two groups, low and normal pretreatment TTS, were treated with medroxyprogesterone acetate (MPA) and compared on clinical response (deviant and nondeviant sexual behaviors; recidivism) and length of time to return to pretreatment TTS after discontinuing MPA. Thirteen paraphilic men who were treated with MPA and had TTS levels monitored at approximately three-month intervals during and after MPA were followed naturalistically. The principal outcome measures pertained to TTS levels and data from a self-report psychosexual inventory, which quantified deviant and nondeviant sexual activities. Time to return to baseline TTS levels were analyzed with Kaplan-Meier survival analysis. Nonparametric methods were used to compare the two groups on other variables. Multiple regression was used to examine the contribution of combinations of variables to TTS outcome. Subjects with low pretreatment TTS received MPA for longer periods of time, and older subjects took longer to return to pretreatment TTS levels despite being treated for shorter periods of time. Although subjects with lower pretreatment TTS levels may be more sensitive to MPA's TTS-suppressive effects, the multiple regression analysis showed that age may be an important determinant of the time it take for TTS levels to return to pretreatment baseline. Sociodemographic, clinical, and self-reported measures of sexual behavior did not distinguish between low and normal TTS level groups. Only one relapse was detected. Further studies with larger samples are required to better understand the role of TTS monitoring of sex offenders treated with MPA, in order to justify its continued use as a measurement of treatment adequacy and to study its potential role as a predictor of treatment outcome.

Age Factors↗
PubMed1996

Medroxyprogesterone acetate treatment reduces serum interleukin-6 levels in patients with metastatic breast carcinoma.

BACKGROUND: The serum interleukin (IL)-6 concentration was very low in patients with metastatic breast carcinoma who had received oral medroxyprogesterone acetate (MPA) treatment as compared with those who had not. Accordingly, the authors conducted a prospective study to determine whether MPA treatment reduces the serum level of IL-6 in patients with this disease. METHODS: In 21 consecutive Japanese patients who were scheduled to receive oral MPA treatment at doses of 600, 800 or 1200 mg/day, serum concentrations of IL-6 were determined with a sensitive enzyme-immunoassay prior to the administration of MPA and again at 4 weeks after the treatment was started. In addition, plasma levels of MPA were determined by high-performance liquid chromatography (HPLC). RESULTS: Four weeks after the oral MPA therapy was started, serum IL-6 levels decreased in all 21 patients regardless of whether or not they responded to the treatment. Although the extent of decrease in the serum IL-6 (delta IL-6) did not correlate with the daily dose of MPA, it correlated closely with the plasma MPA level in these patients. Subjective improvement in appetite and weight gain were more frequent in the delta IL-6 > 3 pg/mL group compared with the delta IL-6 < or = 3 pg/mL group (80% vs. 45% and 70% vs. 45%, respectively). Similar results were obtained for improvement in patients' sense of well-being (100% vs. 55%). CONCLUSIONS: Oral MPA treatment reduces serum IL-6 concentration in patients with metastatic breast carcinoma, but the decrease is not associated with response to MPA. This observation may indicate a potential of this agent for producing subjective improvement.

Administration, Oral↗
PubMed1996

Effects of progestogen on lipids, lipoproteins and apolipoproteins during transdermal estrogen replacement therapy with and without medroxyprogesterone acetate.

OBJECTIVE: To assess whether the effects on plasma lipids and lipoproteins after oophorectomy differ in patients who receive transdermal estrogen replacement therapy (ERT) with and without progestin. STUDY DESIGN: Twenty-five healthy, normal-weight, regularly menstruating women who underwent hysterectomy and bilateral oophorectomy for benign diseases received, for one year, transdermal therapeutic systems containing estradiol with daily delivery of 50 micrograms cyclically for 24 days per month plus 2.5 mg/d of oral medroxyprogesterone acetate (MPA) sequentially for the last 12 days of each cycle. After the first year the patients ceased to take MPA. We determined the levels of cholesterol (CHOL), high density lipoprotein (HDL)-CHOL, low density lipoprotein (LDL)-CHOL, triglycerides (TG) and apolipoproteins (apo) A-I and B prior to oophorectomy, one month after surgery and during the 6th and 12th months on estrogen plus progestogen substitution and during the 18th and 24th months without progestogen addition. RESULTS: After oophorectomy, the patients showed increases in LDL, apo-B and atherogenic index, whereas after hormone replacement therapy the patients exhibited falls in plasma LDL, apo-B and atherogenic index and increases in HDL and apo A-I. No significant changes in total CHOL were observed after surgery or treatment, and TG were decreased. Plasma levels of lipids and lipoproteins during estrogen replacement therapy (ERT) without MPA were not significantly different from those observed during ERT plus MPA. CONCLUSION: Changes in lipids induced by transdermal ERT were not affected by low doses of MPA.

Administration, Cutaneous↗
PubMed1977

Treatment of advanced adenocarcinoma of the endometrium with melphalan, 5-fluorouracil, and medroxyprogesterone acetate: a preliminary study.

Combination chemotherapy can produce a rapid and frequent therapeutic effect against advanced endometrial adenocarcinoma regardless of the tumor distribution. A new treatment program is described. Melphalan, 5-fluorouracil, and medroxyprogesterone acetate achieved 6 of 7 objective responses in patients. This result with combination chemotherapy is substantially better than results with single agents or hormones alone and justifies further evaluation of combinations of cytotoxic chemotherapy as part of the initial treatment of choice for patients with advanced endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed1996

[Does interferon-alpha enhance the effect of tamoxifen-medroxyprogesterone acetate and hydroxyflutamide on in vitro tumor cells?].

In our laboratory the influence of tamoxifen, medroxyprogesterone acetate (MPA) and hydroxyflutamid with and without interferon alpha (IFN) was tested on the proliferative capacity of two breast and one ovarian cancer cell line and three ovarian cancer tissues in the colony assay described by Hamburger and Salmon. The following results were seen: 1. Testing the four drugs alone in 6 different cell cultures, in vitro growth inhibition of more than 30% was seen 3 respectively 4 times. Growth inhibition of more than 50% could be shown only in particular cases. The higher dose of an active substance led up to three times more in comparison to the set growth restraint than the smaller dose. A reaction depending on the concentration was seen. 2. The combination of IFN and tamoxifen could not really increase the antiproliferative capacity of each substance alone. Nevertheless we were able to show a significant augmentation of the cell-growth inhibiting effect of MPA or hydroxyflutamid when it was given together with IFN: the increased antitumor activity was evident if cells were tested which showed progesterone-(PR) or androgenereceptors (AR). The results indicate that positive interactions of IFN and MPA or IFN and hydroxyflutamid are possible. Although an augmentation of the activity of tamoxyfen by IFN was not found it should be stressed that the schedule of treatment seems to be clearly critical.

Androgen Antagonists↗
PubMed1977

Pituitary function in adult males receiving medroxyprogesterone acetate.

The pituitary, adrenal, and gonadal functions of nine males (six XY, two XYY, and one XY/XYY) were studied after at least 6 months of medroxyprogesterone acetate (MPA) therapy for antisocial or sex-offending behavior. Five were studied both before and during therapy, four only during therapy. MPA was effective in decreasing serum gonadotropin and plasma testosterone concentrations. MPA caused no change in the 24-hour rhythm or total integrated concentration of growth hormone. The plasma cortisol circadian rhythm was suppressed but not obliterated by MPA therapy. Although a significant decrease (P less than 0.001) in 24-hour integrated concentrations of plasma cortisol was also found, the rise in the plasma cortisol level after insulin-induced hypoglycemia was unchanged.

Adrenal Cortex↗
PubMed1996

[Activity of endogenous anticoagulants (antithrombin III, protein C and protein S) in women after menopause treated with hormone replacement therapy (transdermal 17 beta-OH estradiol and oral medroxyprogesterone acetate)].

The influence of hormone replacement therapy (HRT) on coagulation system has not been completely explained yet. We measured plasma activities of antithrombin III, protein C and protein S before and after 6 and 12 months of HRT in 48 postmenopausal women. HRT consisted of transdermal estradiol and orally medroxyprogesterone acetate. We observed no statistically significant differences in plasma levels of the above endogenous anticoagulants before and during treatment.

Aged↗
PubMed1998

Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer: a randomized, placebo-controlled trial.

BACKGROUND: Anorexia and cachexia are well-known sequelae of cancer that contribute to morbidity and mortality. In several studies in patients with non-hormone-sensitive tumors, synthetic progestogens were shown to exert beneficial effects on appetite and weight loss. The current study was undertaken to investigate the effects of medroxyprogesterone acetate (MPA) on food intake, body composition, and resting energy expenditure (REE). METHODS: Fifty-four patients with non-hormone-sensitive cancer, generally characterized by substantial weight loss and hypermetabolism, received either MPA, 500 mg, or placebo twice daily for 12 weeks (double-blind study). Food intake was measured by dietary history, body composition was assessed by deuterium dilution (fat mass, fat-free mass), and REE was obtained by indirect calorimetry. RESULTS: Compared with placebo, 12 weeks of MPA led to an increase in energy intake (between-group difference, 426 kcal/day; P = 0.01) that was significantly associated (r = 0.68, P = 0.003) with an increase in fat mass (between-group difference, 2.5 kg; P = 0.009). Fat-free mass was not significantly influenced. REE increased during MPA treatment: at 6 weeks, the between-group difference in change was 135 kcal/day (P = 0.009); after 12 weeks, this difference was 93 kcal/ day (P = 0.07). CONCLUSIONS: The authors conclude that MPA is able to stimulate increased food intake significantly and to reverse fat loss concomitantly in patients with non-hormone-sensitive cancer.

Aged↗
PubMed1997

[A case of dural sinus thrombosis during the medication of medroxyprogesterone acetate].

It is reported that medroxyprogesterone acetate (MPA) causes venous thrombosis as one of the side effects. A 49-year-old woman suffering from metastatic lung carcinoma from breast carcinoma was administered MPA 1200 mg/day for about four months. Thereafter she complained of dizziness about two weeks but the general practitioners could detect no abnormality on physical examinations and on brain CT X-ray findings. Six days later, she died suddenly at her home. Forensic autopsy findings revealed the marked superior sagital sinus thrombosis and the malignant lymphadenomatosis caused by metastatic lung carcinoma. As the patient had not disease or trauma causing dural sinus thrombosis except for the administration of MPA, we concluded that superior sagital sinus thrombosis was due to the medication of MPA. This case illustrates that forensic pathologist should consider the major side effect of some drugs like our case.

Antineoplastic Agents, Hormonal↗