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At least 1,153 records · Page 64Linked to original sources
PubMed1985

Invasive cervical cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Preliminary results of a study of the possible relationship of depot-medroxy-progesterone acetate (DMPA) to invasive cervical cancer are presented. The findings are based on data from three participating centres in Thailand and one in Mexico. A relative risk for cervical cancer of 1.2 was observed in women who had ever used DMPA; this was not statistically significant. No consistent increase in risk with duration of use was observed, although a relative risk of 2 was found in women who had used DMPA for more than 5 years. This observed increase in risk was confined to women who were aged under 46 years or who had first been exposed to DMPA before 30 years of age. These findings are based on small numbers of subjects, and may not represent a causal relationship.

Contraceptive Agents, Female↗
PubMed1983

Medroxyprogesterone acetate as a contraceptive for female drug addicts.

A study of 69 female drug addicts is presented who have been given depomedroxyprogesterone acetate (DMPA) as a contraceptive for 1 680 woman-months. No pregnancies were reported during the treatment period with DMPA. After stopping treatment, 60 pregnancies with 43 births were recorded, 12 with low birth weight. In 3 cases pregnancy ended with spontaneous abortion, and in 14 cases legal abortion were performed. During the study, regular liver function tests revealed no hepatotoxic effects from DMPA in this group of patients where one would expect a high frequency of a serum hepatitis. Neither coagulation nor blood pressure were affected. The most frequent side effect was amenorrhoea, which seems to be accepted well in this group. Metrorrhagia is often a reason for withdrawing the drug. A very high frequency of venereal or other gynaecological infection is presumably the explanation for the very high number of atypical inflammation cells found at vaginal cytological examination. In the series, two cases of carcinoma in situ have been demonstrated by cervical biopsy. Both cases are possibly related to these women's early sexual activity, very promiscuous life and to the poor environment of the drug addict.

Adolescent↗
PubMed1976

[Concentration of estrone, estradiol and estriol in the blood of pregnant sheep after induction of estrus with chlormadinone acetate and medroxyprogesterone acetate].

The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.

Animals↗
PubMed1989

Mammary adenocarcinomas induced by medroxyprogesterone acetate: hormone dependence and EGF receptors of BALB/c in vivo sublines.

Mammary adenocarcinomas were induced by medroxy-progesterone acetate (MPA) in female BALB/c mice. From 5 primary tumors, 9 different sublines were established by s.c. transplantation into syngeneic female mice; these developed after a long latent period (4-12 months). Each subline was transplanted both into 4 mice treated with 40mg of MPA depot (s.c. contralaterally to the tumor inoculum) and into 4 non-treated mice. Of the 9 sublines, 6 proved to be hormone-dependent (MPA-D) and 3 hormone-independent or autonomous (MPA-I). However, even the autonomous lines, when treated with MPA, showed a slight increase in growth. All MPA-D lines had a high content of ER (20-254 fmoles/mg of protein), PR (63-710), PRL-R (44-74) and low or non-detectable EGF-R. Of the 3 MPA-I sublines that were studied, 2 showed a high content of ER (16-125), PR (27-708), PRL-R (19-70) and EGF-R (29-65) while the other one had a low content of ER (0-36), PR (0-13), no EGF-R and moderate PRL-R (15-52). Spontaneous mammary tumors of BALB/c and C3H origin, which also showed an MPA-I pattern of tumor growth, had high levels of EGF-R. We postulate that MPA has a direct effect on mammary tumor cells in MPA-D lines and that the expression of EGF-R is correlated with an autonomous pattern of growth.

Adenocarcinoma↗
PubMed1984

The effect of medroxyprogesterone acetate (Depo-Provera) on prenatal development in the baboon (Papio anubis): a preliminary study.

Six female olive baboons (Papio cynocephalus anubis) were treated with a single dose of 150 mg of Depo-Provera i.m. at day 30 of pregnancy, approximately three times the human dose equivalent on a body weight basis. Fetectomies were performed at day 100 of gestation. The body weights and measurements of the five live fetuses were comparable to age-matched controls and no gross or histologic abnormalities were seen. The dead fetus was in an advanced state of decomposition. This preliminary study suggests that, at levels up to three times that used for human contraception, Depo-Provera does not appear to have any adverse effects on fetal development.

Animals↗
PubMed1985

Embryotoxicity of a single dose of medroxyprogesterone acetate (MPA) and maternal serum MPA concentrations in cynomolgus monkey (Macaca fascicularis).

A single dose of MPA (Depo-Provera; Upjohn Co., Kalamazoo, Michigan) was administered intramuscularly to 12 time-mated pregnant cynomolgus monkeys on day 27 (+/- 2) of gestation at 25 mg/kg or at 100 mg/kg. Maternal blood samples were collected immediately prior to MPA injection and then at regular intervals until cesarean section at term (day 152 +/- 3). Infants in both dose groups had external genital abnormalities. Female infants in the low-dose groups had partial or complete labial fusion, prominent median raphe, and clitoral hypertrophy; at high doses (100 mg/kg), the female infants had complete labial fusion and a distinct penile urethra. MPA had an opposite effect on external genitalia of male infants. The penis was short and the scrotal swelling was absent or less conspicuous, and two males had hypospadias. The adrenal glands were significantly smaller (P less than 0.05) in infants of both sexes treated with 100 mg/kg. One of the infants treated with 25 mg/kg of MPA had a muscular ventricular septal defect. Serum concentrations of MPA were determined by radioimmunoassay in eight pregnant monkeys. In the 25 mg/kg group the patterns of MPA profiles in the serum were similar in all four animals. An initial peak occurred at 24-48 hr postinjection (2.7-9.6 ng/ml), followed by a slight decrease at 3 days postinjection (gestational day 30), and then a steady increase to maximum levels of 10-14 ng/ml occurring between gestational days 37 and 50. Serum levels gradually declined to concentrations below 5 ng/ml by midgestation in three of four monkeys. By comparison, both the patterns and magnitude of MPA concentration showed great interanimal variation in the 100 mg/kg group. MPA was present in cord blood at measurable concentrations in infants at both dose groups; the levels ranged from 0.6 to 8.3 ng/ml, corresponding to 40-72% of the maternal concentrations. These results demonstrate that a single injection of MPA during early pregnancy causes selective embryotoxicity in both male and female fetuses. Presence of high levels of MPA in maternal sera during the critical period of genital development can cause specific genital defects; however, the exact mechanism by which MPA causes these paradoxical genital abnormalities is unknown.

Abnormalities, Drug-Induced↗
PubMed1984

Adrenal suppression by oral high-dose medroxyprogesterone acetate in breast cancer patients.

The effects of oral MPA, 300 mg t.i.d., on adrenal function in postmenopausal patients with disseminated breast cancer were evaluated. The levels of serum cortisol, ACTH, androstenedione, DHEA-S, LH, FSH, GH, and prolactin in 22 patients receiving MPA were compared with those in another group of 28 postmenopausal patients in whom levels were measured before treatment. The median morning cortisol level was 70, 10-465 nmol/l (controls 395, range 155-785 nmol/l), median androstenedione 1.09, range 0.55-3.10 nmol/l (controls 3.75, range 1.23-9.81 nmol/l), and median DHEA-S 555, range 55-1,300 nmol/l (controls 2,440, range 1,015-6,340 nmol/l). No appreciable change in ACTH levels was found. Gonadotropins were also markedly suppressed. The median LH level was 4.3 (range 0.8-18) U/l, as against 83 (range 19-116) U/l in controls. The median FSH level was 7.2 (range 0.5-27) U/l, as against 71 (range 12-262) U/l in controls. Prolactin and GH levels remained largely unchanged. The suppression of androstenedione synthesis, the main precursor of postmenopausal estrogens, may represent the major therapeutic effect of high-dose MPA in postmenopausal patients with breast cancer.

Adrenocorticotropic Hormone↗
PubMed1983

A phase II study of high-dose medroxyprogesterone acetate in advanced breast cancer.

Twenty-three evaluable patients with advanced breast cancer were treated with MPA, 1,400 mg/m2 daily PO for the first 6 months, and 500 mg/m2 daily PO thereafter. The median total dose was 191,400 mg in 88 days, with the maximum dose given to date 522,600 mg in 282 days. Most patients tolerated high-dose MPA well. Side-effects were minimal and reversible. The commonest side-effects were tremor or edema. The CR plus PR rate was five of 23 (22%). All responding patients were over 50 years of age and had a good performance status. Hormone receptor status was known in four patients only, so that no correlation between receptor status and response could be drawn. MPA appears to be a useful hormone for use in the management of breast cancer. Optimal dosage remains to be determined.

Adult↗
PubMed1985

Mechanism of adrenal suppression by high-dose medroxyprogesterone acetate in breast cancer patients.

To investigate the mechanism of adrenal suppression by high-dose MPA, we performed direct and indirect stimulation tests in postmenopausal women with disseminated breast cancer who were receiving MPA and in a postmenopausal breast cancer control group. A partial adrenal insufficiency was found during Synacthen stimulation, confirmed by a slight increase of 11-desoxycortisol after metyrapone, despite a sufficient rise in ACTH levels. Peak levels of androstenedione and 17-OH progesterone after Synacthen correlated with those after metyrapone. Peak cortisol levels after Synacthen also correlated with the sum of cortisol and 11-desoxycortisol values after metyrapone, indicating the presence of a maximum adrenal response and a sufficient rise of endogenous ACTH after metyrapone. As the peak levels of cortisol and androstenedione were highly correlated with baseline values, a short Synacthen stimulation test may give a good indication as to whether adrenal suppression by MPA is adequate. The adrenal androgen androstenedione is the precursor of the main postmenopausal oestrogen, oestrone. In this way, adrenal suppression may constitute an important therapeutic effect of high-dose MPA.

17-alpha-Hydroxyprogesterone↗