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Treatment of obsessive homosexual pedophilic fantasies with medroxyprogesterone acetate.

The author describes a male patient with obsessive homosexual pedophilic fantasies treated with psychotherapy and medroxyprogesterone acetate (MPA), a progestin with antiandrogen activity. Long-acting MPA was administered for a 2-month period and caused a prompt and drastic reduction in fantasies and in the anxiety and depression generated by them. MPA was observed to have psychological benefits that outlived its physiologic activity.

Adult↗

Effect of medroxyprogesterone acetate on hepatic lipid profile of female rats under various states of nutrition.

The effect of medroxyprogesterone acetate (MPA) treatment on hepatic lipid profile was studied in female rats kept on protein-deficient diet, on normal restricted diet and on normal, ad libitum diet. A significant decline in total and free cholesterol levels was observed in rats kept on protein-deficient diet and on normal, restricted diet. However, protein-deficient animals exhibited a significant rise in the liver triglyceride level. In rats on normal, ad libitum diet only, MPA treatment resulted in elevated levels of triglycerides and increased esterification of cholesterol. This was mostly due to increased incorporation of acetate into esterified cholesterol and triglyceride as evident from studies using the labelled precursor. Total phospholipid content was found to be unaffected by MPA in all the groups suggesting that the drug and dietary protein level have no effect on hepatic phospholipid content.

Animals↗

Chemo-hormonal therapy for metastatic renal cell carcinoma with adriamycin, hydroxyurea, vinblastine, and medroxyprogesterone acetate.

In a phase II study, eight patients with metastatic renal cell carcinoma have been treated with a combination of chemotherapy and hormonal therapy using adriamycin, hydroxyurea, vinblastine, and medroxyprogesterone acetate. Five patients have responded, including one with complete response, one with subjective improvement, and three with partial responses. The median survival was 4 months with a range of 4--11 months. With the exception of mild alopecia and nausea, toxicity was minimal; no significant hematologic toxicity was noted. The initial results of this study suggest that chemo-hormonal therapy plays a significant role in the management of renal cell carcinoma.

Adenocarcinoma↗

Medroxyprogesterone acetate (MAP) relative bioavailability after single high-dose administration in cancer patients.

A pharmacokinetic evaluation of medroxyprogesterone acetate (MAP, 6 alpha-methyl-17 alpha-hydroxyprogesterone acetate) was undertaken in 70 patients with advanced cancer treated either orally or im with single high doses. MAP plasma levels were determined by gas chromatography (63Ni electron capture detector) after derivatization with heptafluorobutyric anhydride, using 17 alpha-hydroxyprogesterone caproate as internal standard. Plasma levels after oral administration can be approximated by a triexponential function in agreement with a pharmacokinetic two-compartment open model with first-order absorption; peak levels are dose-related, but high interindividual variance is present. Following the administration, both decay phases are masked by prolonged absorption; peak levels are lower than after oral administration, but long-term bioavailability is higher, as demonstrated by comparison of the values for areas under curves in the 0-146-hour interval. The high interindividual ranges in the observed MAP plasma levels indicate that if any significant clinical evaluation is to be made, routine analysis of plasma MAP is mandatory.

Administration, Oral↗

[Immunodepressive action and effects of medroxyprogesterone acetate on the lymphatic tissue of the spleen of rabbits].

Present results demonstrated that medroxyprogesterone acetate (MPA) caused depletion of lymphoid splenic tissue in rabbits. This phenomenon, induced by corticoid action and antiproliferative activity of the hormonal agent, supported the immunodepressive properties of drug, which prolonged the survival of some allografts and lowered the antibody response to different antigens.

Animals↗

[Urinary hydroxyproline in advanced breast carcinoma and response to treatment with medroxyprogesterone acetate (MAP) in high doses].

The Authors have studied total urinary hydroxyproline (TUH), together with other hematochemical analyses, in 104 patients suffering from advanced breast cancer with or without bone metastases. TUH escretion is higher in patients with osseous lesions and, if simultaneous pathologic values of TUH and serum alcaline phosphatase occur, the presence of bone metastases is statistically even more probable. Moreover TUH seems to vary in accordance with the clinical response of the disease at osseous level in 46 patients treated with Medroxyprogesterone acetate (MPA) at high doses, showing itself as a possible marker of not negligible clinical value.

Adult↗

[Results of a pilot study with high-dose medroxyprogesterone acetate in the treatment of metastasizing breast carcinoma].

Nineteen patients with advanced breast cancer were treated with 1 g medroxyprogesterone acetate (MPA) i.m. daily for 4 weeks. The therapy was well tolerated. The measurable tumor lesions showed a regression of more than 50% in 6 cases; the mean duration of remission was 12 months. In 12 patients the treatment led to a marked subjective improvement. On the basis of these data the authors feel that high-dosage MPA warrants further investigation in the treatment of metastatic breast cancer.

Aged↗

Medroxyprogesterone treatment for paraphiliacs.

This study addresses the following questions: (1) what are the essential components of a medroxyprogesterone acetate (MPA) pretreatment evaluation?; (2) do paraphilic men treated with MPA (Depo-Provera) report a lowering of both deviant and nondeviant sexual drive and activities?; (3) is behavioral improvement associated with testosterone level reductions?; and (4) what significant side effects are associated with MPA treatment? A total of 29 paraphilic men who underwent a comprehensive psychiatric, medical, and legal evaluation and were eligible for treatment with MPA were followed naturalistically while receiving concurrent MPA and group therapy. The principal outcome measures were data obtained from a weekly self-reported psychosexual inventory that quantified five dimensions of deviant and nondeviant sexual activities and testosterone levels that were drawn pretreatment and after three and six months of MPA. Self-reported data were analyzed by nonparametric methods. Because MPA's effectiveness is evident early in treatment, we report on data from the first six months. Subjects reported a differential rate of suppression of sexual activities, a median of up to two weeks for deviant and 2 to 10 weeks for nondeviant behaviors (p < or = .01 for each of the five dimensions). Testosterone levels suppressed to less than 0.5 ng per milliliter for all but two subjects at three months and for all at six months. Recidivism was reported for one subject. Except for one subject who developed pulmonary emboli, no major medical problems were encountered. MPA safely and effectively reduced sex drive, controlled deviant sexual impulses and behavior, and lowered the testosterone levels of these paraphilic men during the first six months of treatment. However, the relative rapidity and completeness of the response raises questions regarding possible distortions in self-reported sexual activities. This should alert the practicing clinician to consider the use of collateral sources of information in interpreting treatment outcome for patients with paraphilic behaviors. Also, longer follow-up periods are required for monitoring treatment efficacy.

Adolescent↗

Postmenopausal hormone replacement therapy with low-dose medroxyprogesterone acetate. Endometrium, plasma lipids, lipoproteins and apolipoproteins.

Several studies have demonstrated that the use of estrogens in postmenopausal women has a protective effect against cardiovascular disease; however, this beneficial effect may be counteracted when concomitant progestogens are administered. We investigated the influence of hormone replacement therapy (HRT) with lower doses of medroxyprogesterone acetate (MPA) (2.5 mg/d) on the endometrium and on the plasma levels of lipids, lipoproteins and apolipoproteins. All the studied HRT regimens induced favorable changes in the levels of plasma lipids, lipoproteins and apolipoproteins, which may play an important role in the prevention of cardiovascular disease. The dosage of 2.5 mg/d of MPA is clearly inadequate to protect the endometrium from hyperplastic changes with sequential regimens, but probably this dosage is safe when MPA is administered continuously.

Adult↗

Oral high-dose medroxyprogesterone acetate treatment for recurrent breast cancer.

Oral high-dose medroxyprogesterone acetate (MPA) treatment (600, 800, 1200 mg/day or changed dosage) was given to 49 patients with recurrent breast cancer from January 1979 to December 1992. The overall response rate to MPA was 38.8% (19/49). The response rate in the soft tissue was significantly higher compared with that in bone metastases or in visceral metastases. MPA was effective on patients both with or without previous treatment. Several side effects were recognized, but they were mild and tolerable. These results demonstrate that MPA is effective when used as first line or second line treatment.

Administration, Oral↗

Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin resistant human breast cancer cell line.

In malignant cells multidrug resistance (MDR) is frequently associated with the expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts as an ATP-dependent efflux pump causing a decreased intracellular accumulation of structurally unrelated natural anticancer agents such as anthracyclines. Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene product P-gp. In our experiments the revertant activity of medroxyprogesterone acetate (MPA) in comparison to that of the well known revertant agent verapamil (VRP) was investigated. In vitro tests were carried out on a DX-resistant variant (CG5/DX) obtained in our laboratory from the parental CG5 human breast cancer cell line by continuous exposure to the drug. The ability of MPA to modulate intracellular DX accumulation and to reverse MDR was evaluated. MPA appeared more active than VRP in reversing MDR, suggesting a possible role of this synthetic progestin as chemosensitizing agent in the clinical management of anthracycline-resistant breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The effect of combination treatment consisted of 5'-deoxy-5-fluorouridine and medroxyprogesterone acetate for recurrent breast cancer patient].

The effect of the combination treatment consisted of 5'-deoxy-5-fluorouridine (5'-DFUR) and medroxyprogesterone acetate (MPA) was investigated in 20 recurrent breast cancer patients. Out of 20 patients, 8(40.0%) responded to the treatment. The average duration of response was 10.3 months. Response rates stratified by recurrence site were soft tissues 36.4%, bone 44.4%, liver 60.0% and lung 20.0%, respectively. No serious side effect except body weight gain, which was caused by MPA, was seen. In a 76-year-old woman with liver metastases, a marked response was obtained and has continued for more than 24 months. It was suggested that the combination of 5'-DFUR and MPA may be effective for recurrent breast cancer patients.

Administration, Oral↗

Morphological and biochemical features of a medroxyprogesterone acetate (MPA)-resistant MCF-7 breast cancer cell line.

An MCF-7 human breast cancer line variant (MCF-7/MPA), resistant to medroxyprogesterone-acetate (MPA), was obtained by continuous exposure in vitro to the drug. MCF-7/MPA cells were grown in the presence of 12.5 x 10(-6) M MPA and were selected by increasing the concentration of the drug in the growth medium in a stepwise manner from 0.025 x 10(-6) M up to 12.5 x 10(-6) M. Comparative studies of cellular morphology, cytosolic steroid receptor content and P-Glycoprotein expression were performed on both MCF-7 parental line and MCF-7/MPA variant. MCF-7/MPA cells, when compared to the parental line, exhibit a different morphology in terms of membrane alterations, reduced content of cytosolic progesterone receptor, increased expression of P-glycoprotein along with reduction of Doxorubicin (Dx) activity on the growth of MCF-7/MPA resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A prospective study of adolescents who choose among levonorgestrel implant (Norplant), medroxyprogesterone acetate (Depo-Provera), or the combined oral contraceptive pill as contraception.

OBJECTIVES: Levonorgestrel implants (Norplant) and medroxyprogesterone acetate injections (Depo-Provera) represent additional contraception options for adolescents. The purpose of this study was to examine prospectively clinical profiles among adolescents who chose one of the two long-term contraceptives compared with profiles among those who chose the combined oral contraceptive pill (OCP). METHODS: Girls who needed contraception and did not require confidentiality were presented with a contraceptive menu consisting of Norplant (n = 58), Depo-Provera (n = 66), or OCP (n = 75). At baseline and follow-up visits over 6 months, patients were interviewed regarding gynecologic history, side effect symptoms, and satisfaction. The average age of subjects was 15.5 years (range 11 to 20 years); 66% were African-American and 34% white. RESULTS: Significantly more teens who chose Depo-Provera (73%) reported having used some method of birth control previously than those selecting either Norplant (30%) or OCP (26%). Adolescents who chose either Norplant (34%) or Depo-Provera (43%) were significantly more likely to have been pregnant previously than those choosing OCP (12%). Those selecting Depo-Provera were significantly more likely to report a history of genital infection with Chlamydia trachomatis (42%) than those in the other two contraceptive groups (22%). Prevalences of reported recent depression and fatigue before initiation of treatment were high, exceeding 35% across the three groups. A total of 105 and 40 adolescents were assessed at 3 and 6 months, respectively. At follow-up, more than 80% of OCP users maintained regular menstrual cycles, whereas over 80% of those choosing Norplant or Depo-Provera had disrupted cycles. Complaints of nausea and dizziness among Norplant users and fatigue among Depo-Provera and OCP users increased significantly between the baseline and follow-up visits. Reports of local reactions to the Norplant device were common but not clinically significant. Blood pressure readings, facial acne, and body mass index did not change over time in any treatment group. Subjects in the Norplant and Depo-Provera groups appreciated freedom from daily compliance to maintain contraceptive effectiveness and the "hidden" nature of the method. Appointment compliance at the end of 6 months was 78% for Depo-Provera, 40% for Norplant, and 46% for OCP. CONCLUSIONS: The implant and injection forms of contraception appear to be especially popular among girls with previous pregnancies or birth control use. The common occurrences of medical symptoms and sexually transmitted diseases before initiation of therapy underscore the importance of baseline evaluation. Norplant users may be warned about nausea and dizziness as well as minor local symptoms around the insertion site and unpredictable uterine bleeding patterns. Adolescent patients choosing Depo-Provera may expect amenorrhea by the end of 6 months of therapy along with possible fatigue. Early intervention may be needed with adolescents who choose Norplant or OCP to encourage better compliance with follow-up appointments.

Adolescent↗

[A case of metastatic breast cancer successfully treated with weekly low-dose epirubicin (EPI), cyclophosphamide (CPA), 5-fluorouracil (5-FU) and medroxyprogesterone (MPA)].

We reported a case of successful treatment of disseminated breast cancer with epirubicin (EPI), 5-fluorouracil (5-FU), and medroxyprogesterone (MPA). The patient was a 49-year-old female with bone and liver metastasis developed 5 years after surgery. The primary tumor was ER-positive, and she had been treated previously with adjuvant therapy using UFT and tamoxifen. The treatment consisted of 3 cycles of thrice-weekly EPI (40mg), 5-FU (500mg) and CPA (500mg). The patient was then treated with a weekly schedule of EPI (10mg), 5-FU (50mg/day), CPA (50mg/day) and MPA (400mg/day). After 2 years, her bone and liver metastasis showed remarkable remission (PR). No side effects of this chemotherapy were observed. In the search for palliative treatments which have a minimal impact on normal lifestyle, low toxicity is important. PR was continued for 2 years, and the patient enjoyed a favorable quality of life. This low dose-weekly approach was very well tolerated, yet was effective.

Adenocarcinoma↗

[2d and 3d line hormonal therapy in postmenopausal metastatic breast tumor. Comparison of medroxyprogesterone acetate and aminoglutethimide in tamoxifen-resistant patients].

In order to evaluate the effectiveness of second and third line hormone therapy for postmenopausal (spontaneous or surgical) women with metastatic tamoxifen-resistant breast cancer, 293 women aged 36 to 91 (mean 63.6) were divided into two groups submitted to a multicenter study of two treatment schedules: a) Aminoglutethimide (AG; 500 mg daily plus hydrocortisone 40 mg daily); b) Medroxyprogesterone (MPA; 1,000 mg daily per os). Of the 293 patients receiving second line hormone therapy, only 161 were available for third line treatment. In phase 1, 153 patients were treated with AG: 36% had objective responses (complete or partial); of 140 patient receiving MPA, 33% had objective responses (p = 0.045, significant). In the AG-treated group, duration of response was 11.3 +/- 8.4 months as against 8.3 +/- 5.6 months in the MPA group (p = 0.07, significant). In phase 2, 87 women previously treated with MPA received AG, and 74 previously AG-treated patients were given MPA. There were no significant differences in the results obtained. In conclusion, there were no significant differences in the results obtained by AG and MPA treatment as far as toxicity and survival was concerned but there was a statistically significant advantage for AG as second and third line management both as to objective responses and mean time until renewed progression of the disease.

Adult↗

Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. The Menopause Study Group.

OBJECTIVE: To evaluate the impact of different dosages of medroxyprogesterone acetate (MPA) on metabolism and hemostasis in postmenopausal women treated with conjugated estrogens. METHODS: In this prospective, double-blind study, 525 women were randomized to five treatment groups at 26 sites in the United States and Europe. All participants received 0.625 mg conjugated estrogens daily for up to 13 cycles; four groups also received MPA, either 2.5 or 5.0 mg/day continuously or 5.0 or 10.0 mg/day for the last 14 days of each cycle. Effects on lipid and carbohydrate metabolism and coagulation were evaluated. RESULTS: Beneficial changes in plasma lipid levels occurred in all groups, but were greatest with conjugated estrogens alone (P < or = .05). Fasting glucose and insulin levels were significantly lower and the insulin response to glucose challenge was significantly blunted in all groups (P < or = .05). No major changes of clinical significance occurred in hemostatic levels. CONCLUSIONS: Metabolic levels were not affected adversely by the addition of MPA to conjugated estrogens, but some beneficial changes were greater with conjugated estrogens alone. Hemostatic levels were not affected.

Aged↗

Induced prolactin release in women under long-term medroxyprogesterone acetate treatment.

Medroxyprogesterone acetate (MPA) was administered, as a contraceptive, by intramuscular injection in doses of 150 mg every 90 days, or 300-450 mg every 180 days, to 5 women, over a period of 27 to 42 months. No major adverse reactions were reported, and the minor side effects were only as frequent as those reported for oral contraceptives. The LH basal levels were depressed in all subjects;; FSH and prolactin serum concentrations were within the range found in normally cycling women. Synthetic TRH released prolactin in 4 subjects, and the maximal response was within 10-20 minutes after TRH injection. In the fifth case there was no prolactin release.

Acetates↗