Combination Of Medroxyprogesterone Acetate Research Articles

Regulation of Prolactin Production by Progestin, Estrogen, and Relaxin in Human Endometrial Stromal Cells*

Human decidua synthesizes and secretes PRL. We identified the PRL synthesized in endometrial stromal cells and investigated the effect of medroxyprogesterone acetate (MPA), estradiol (E2), porcine relaxin (RLX), and RU486, an antiprogestin, on PRL production by stromal cells from non-pregnant endometrium in primary culture. Stromal cells were isolated from proliferative and secretory endometria and individually cultured in nutrient medium or medium supplemented with different hormone(s). The immunoreactive PRL isolated from culture medium of hormone-stimulated stromal cells was identified and compared to pituitary PRL. Bio-Gel elution pattern and mol wt analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting showed that PRL produced by stromal cells had properties identical to those of pituitary PRL. In addition, PRL mRNA was identified in hormone-stimulated stromal cells using human pituitary PRL cDNA as a hybridization probe. Analysis of mRNA by Northern blotting showed that the size of PRL mRNA isolated from stromal cells was indistinguishable from that of PRL mRNA in human decidua and pituitary tissue. These results indicated that PRL measured in culture medium was synthesized de novo by stromal cells. The PRL content in culture medium was quantitated by RIA. The PRL production rate in stromal cells cultured without hormones ranged from 6-10 ng/day.mg cell protein. After 4-5 days of incubation with RLX or MPA alone, the PRL production rate increased about 2- to 3-fold over the control value. E2 alone had either no effect or slightly decreased the stromal cell PRL production rate. Stromal cells responded to 0.02 microM MPA, and the maximal response was at 0.1-1 microM MPA. A further increase in PRL production was found when stromal cells were treated with a combination of MPA and E2 and MPA, E2 and RLX. In the presence of MPA or MPA and E2, 0.1 ng/ml relaxin increased the PRL production rate. A potent progestin antagonist, RU486, inhibited PRL production in stromal cells treated with MPA, MPA and E2, or MPA and RLX. These results indicate that endometrial PRL production is regulated by the combined effects of steroid hormones (progestin and estrogen) and a peptide hormone (relaxin).

Use of medroxyprogesterone acetate in treatment of a deaf‐mute sex offender

Medroxyprogesterone acetate in combination with counseling has been reported to help sex offenders gain control of their maladaptive behavior (Barry & Ciccone, 1975; Berlin & Meinecke, 1981; Cordoba & Chapel, 1983; Gagne, 1981; Herrman & Beach, 1980; Money, 1970; Money et al., 1975; Money & Bennett, 1981). Medroxyprogesterone acetate is an antiandrogenic agent that can be administered intramuscularly to be gradually absorbed into the bloodstream, causing a decrease in the circulating levels of testosterone. It is a drug used frequently in the United States to treat paraphiliac patients. Medroxyprogesterone acetate reduces the frequency of erections and ejaculation. Besides inhibiting the release of androgen from the testicles, medroxyprogesterone acetate is believed to act on the brain to decrease sexual fantasies and decrease the intensity of erotic urges (Berlin & Meinecke). There are few cases in the literature pertaining to cognitively impaired or mentally deficient sex offenders who have been treated successfully with medroxyprogesterone acetate. One case involved a 14-year-old boy with epilepsy of the Lennox-Gastaut type and mental retardation (Blumer & Migeon, 1975). He had exhibited both hostile and sexual aggressiveness and showed some response to the medication, but he was admitted to a psychiatric hospital before the treatment was fully effective. The medication was discontinued in the hospital. Another case involved a brain-damaged patient who masturbated excessively (Blumer & Migeon). He showed improvement while on medroxyprogesterone acetate, but treatment was discontinued after 2 months when a seizure disorder returned. The excessive sexual arousal was controlled without further antiandrogenic medication. We report the case of a deaf-mute, aphasic patient with offensive sexually aggressive behavior who responded to medroxyprogesterone acetate.

High-dose medroxyprogesterone acetate in combination with vindesine in advanced breast cancer

Forty-three evaluable women with metastatic breast cancer received treatment with high-dose medroxyprogesterone acetate (MPA) plus vindesine. Patients tolerated treatment well, no lethal toxicities occurred. The commonest side-effects were hemopoietic, with leukopenia documented in 22 patients. Symptoms of peripheral neuritis occurred in 10 patients. A response rate of 28% ( 12 out of 43 patients) was seen. Ten of the responding patients had multiple prior chemotherapeutic agents. These results indicate that the combination of MPA and vindesine is not of value in patients with advanced breast cancer.

The effect of oral medroxyprogesterone acetate and methyltestosterone on sexual functioning in a male contraceptive trial

Twenty-three men who participated in a 15-month clinical trial to assess the potential effectiveness of using a combination of varying doses of medroxyprogesterone acetate (MPA) and methyltestosterone (MT) as a male contraceptive agent, completed a “sexual problem checklist” every two weeks. The study was divided into three phases: pre-treatment (3 months), treatment (6 months), post-treatment (6 months). The questionnaire evaluated changes in various aspects of sexual behaviour and sexual perception and explored whether the treatment influenced any of the parameters considered. The results indicated a small, but significant, decrease in subjective assessment of sexual drive. This was not, however, accompanied by a change in sexual behaviour, in that subjects experienced the same number of erections, ejaculations and frequency of intercourse. It is concluded that the combination of MPA and MT in the doses used may produce a slight decrease in subjective assessment of sexual drive, but no change in actual sexual behaviour.

Spermatogenesis in Men Treated with Injections of Medroxyprogesterone Acetate Combined with Testosterone Enanthate

The effects of a combination of medroxyprogesterone acetate and testosterone enanthate, on the exocrine and endocrine testicular function were examined in adult men. The treatment was carried out with 2 different regimens and lasted for 8 months. Group I received an initial injection of 1000 mg medroxyprogesterone acetate and 500 mg testosterone enanthate followed by monthly maintenance dose of 150 mg medroxyprogesterone acetate and 500 mg testosterone enanthate. In group II, after an initial high dose of 1000 mg medroxyprogesterone acetate and 250 mg testosterone enanthate treatment was given as biweekly injections of 75 mg medroxyprogesterone acetate and 250 mg testosterone enanthate. Complete spermatogenic arrest of variable duration was achieved in all 9 subjects enrolled. Restoration of spermatogenesis occurred in both groups, in a few cases during the treatment, and there was a delay of full recovery of sperm counts up to 5 months after cessation of therapy. None of the subjects enrolled in this study complained of decrease in libido or change in sexual behaviour. Clinical evaluation and measurements of various urine and serum components revealed no significant changes during the treatment period. The dosage and the different administration schedule of the hormone combination described here was inadequate to maintain azoo-spermia in all subjects during treatment.

Spermatogenesis in men treated with injections of medroxyprogesterone acetate combined with testosterone enanthate.

The effects of a combination of medroxyprogesterone acetate and testosterone enanthate, on the exocrine and endocrine testicular function were examined in adult men. The treatment was carried out with 2 different regimens and lasted for 8 months. Group I received an initial injection of 1000 mg medroxyprogesterone acetate and 500 mg testosterone enanthate followed by monthly maintenance dose of 150 mg medroxyprogesterone acetate and 500 mg testosterone enanthate. In group II, after an initial high dose of 1000 mg medroxyprogesterone acetate and 250 mg testosterone enanthate treatment was given as biweekly injections of 75 mg medroxyprogesterone acetate and 250 mg testosterone enanthate. Complete spermatogenic arrest of variable duration was achieved in all 9 subjects enrolled. Restoration of spermatogenesis occurred in both groups, in a few cases during the treatment, and there was a delay of full recovery of sperm counts up to 5 months after cessation of therapy. None of the subjects enrolled in this study complained of decrease in libido or change in sexual behaviour. Clinical evaluation and measurements of various urine and serum components revealed no significant changes during the treatment period. The dosage and the different administration schedule of the hormone combination described here was inadequate to maintain azoospermia in all subjects during treatment.

The combined use of oral medroxyprogesterone acetate and methyltestosterone in a male contraceptive trial programme

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyl-testosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control — 3 months, treatment — 6 months, follow-up — 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently.Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg, MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size.We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive purposes and that higher doses may induce severe and undesirable side-effects.

The Effect of an Oral Contraceptive on Tests of Thyroid Function

To determine the effect of a combined oral progestin on 5 tests of thyroid function, 21 parous women at least 8 weeks postpartum and with histories of regular menses were studied. A complete physical examination showed all to be normal. The 5 tests performed were radioactive iodine uptake (RAI) at 2 and 24 hours, serum protein-bound iodine (PBI), thyroxine iodine by column, triiodothyronine absorption test, and serum cholesterol. 2 baseline determinations of each test except the RAI were performed on each subject on separate days. Only euthyroid subjects were further tested. Of these 16 were given 10 mg of medroxyprogesterone acetate in combination with .05 mg of ethinyl estradiol cyclically for 20 days. Thyroid function tests were repeated at various intervals from the end of the first week of therapy to over 4 months after starting therapy. Cholesterol and RAI determinations were extremely variable precluding any evidence of drug effect. The other 3 tests showed consistent changes in all patients studied. The serum PBI and thyrozine-iodine by column tests both showed slight elevation within the first week of therapy and further elevation 1 months thereafter. These changes approached hyperthyroidism levels. The triiodothyronine absorption test showed little change in the first week but a definite downward shift thereafter with a maximum depression at 3 months of therapy. This change reached hypothyroidism level. If test were done during the 1 week each month patients were not taking the drug, results were the same. These changes are thought to be due to the estrogen component of the contraceptive drugs. Those physicians depending on these thyroid tests for diagnosis should be aware of these changes in patients taking these drugs.

The effect of certain progestins and estrogens on the threshold of electrically induced seizure patterns.

The purpose of this preliminary study was to examine the interactions of certain anovulatory agents with the seizure thresholds of experimental animals to obtain further information on the mechanisms involved in the alterations of these thresholds. In female albino rats electroshock thresholds were determined. Drugs were administered and 3 parameters weight stage of estrus and electroshock threshold were measured. The drugs administered intraperitoneally were: estradiol benzoate progesterone desoxycorticosterone trimethylacetate (DOCT) medroxyprogesterone acetate (MPA) MPA plus ethinyl estradiol norethynodrel plus mestranol. In 16 mongrel cats of either sex after-discharge seizure threshold was determined. Drugs tested were progesterone MPA and a combination of norethynodrel and mestranol. In rats the electroshock itself had no effect on either the estrous cycle or the weight gain of the animals. Saline administration also produced no effect on the cycle or weight but it did cause a slight but insignificant decrease in the threshold. A single dose of estradiol benzoate produced a rise followed by a sharp decrease in the estrous count. Weight gain was normal and the threshold decreased slightly and then returned to normal. Daily administration of estradiol caused all the animals to go into estrus followed by a prolonged metestrus. A single dose of progesterone resulted in a slight decrease in estrous count which then returned to normal. Daily administration of progesterone did not alter any of the parameters measured. MPA had no effect on weight gain but completely depressed the estrous cycle. The combination of MPA and ethinyl estradiol in the ratio of 200:1 did not completely depress the estrous cycle in all animals but did decrease weight gain. The decrease in the electroshock threshold was significant (p less than .05). Norethynodrel plus mestranol (66:1) caused an elevation in the estrous count which then fell to normal while weight gain was irregular but depressed. There was a significant fall in electroshock threshold. Changing the ratio to 25:1 of the 2 drugs produced a more profound effect. The effects of the test drugs on the afterdischarge seizure threshold of cats were similar to those seen in the rat studies.