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PubMed1994

The effects of hormonal replacement therapy on insulin sensitivity in surgically postmenopausal cynomolgus monkeys (Macaca fascicularis).

OBJECTIVE: Our purpose was to evaluate the effect of hormone replacement therapy on insulin resistance in postmenopausal cynomolgus monkeys (Macaca fascicularis). STUDY DESIGN: We studied 37 surgically postmenopausal cynomolgus monkeys that were fed a moderately atherogenic diet for 12 weeks with either no treatment (control), conjugated equine estrogens, medroxyprogesterone acetate, combination conjugated equine estrogens and medroxyprogesterone acetate, or tamoxifen. Insulin sensitivity and glucose effectiveness were determined by the frequent-sampling intravenous tolerance test by means of the minimal model analysis. RESULTS: There were no differences in body weight, total plasma cholesterol, or body fat distribution between control and conjugated equine estrogens, medroxyprogesterone acetate, or combination treatment groups. However, compared with control animals (insulin sensitivity = 5.9 +2- 1.2 x 10(-4) min-1 microU-1 ml) or conjugated equine estrogens treatment (6.3 +/- 1.1 x 10(-4) min-1 microU-1 ml) insulin sensitivity was significantly decreased in animals treated with medroxyprogesterone acetate (2.9 +/- 0.4 x 10(-4) min-1 microU-1 ml, p < 0.001) or conjugated equine estrogens and medroxyprogesterone acetate (2.8 +/- 0.6 x 10(-4) min-1 microU-1 ml, p < 0.001). Although insulin sensitivity was shown to be decreased in the tamoxifen-treated animals (insulin sensitivity = 4.6 +/- 0.6 x 10(-4) min-1 microU -1 ml), the difference was not statistically significant compared with the control or conjugated equine estrogens-treated animals. No significant differences were seen for glucose effectiveness comparing control animals (glucose effectiveness = 0.043 +/- 0.006 min-1) to animals treated with medroxyprogesterone acetate (glucose effectiveness = 0.046 +/- 0.009 min-1), conjugated equine estrogens and medroxyprogesterone acetate (0.048 +/- 0.008 min-1) or tamoxifen (0.039 +/- 0.006 min-1). CONCLUSION: These results suggest that progestins alone or in combination with estrogens can induce insulin resistance in postmenopausal monkeys while having no effect on plasma lipid concentrations or glucose effectiveness.

Animals↗
PubMed1977

Role of hormones in growth kinetics of renal cell carcinoma in vitro.

Medroxyprogesterone acetate has been used to treat metastatic renal cell carcinoma largely because of its observed inhibitory effects on the growth of estrogen-induced tumors in male Syrian golden hamsters. The absence to date of any successful, established chemotherapeutic regimen in the management of metastatic renal cell carcinoma has led to the continued application of medroxyprogesterone acetate in the majority of patients with this disease because of the occasional regression witnessed (particularly in male patients) and the absence of untoward side effects. To examine the mechanism of action of medroxyprogesterone acetate renal cell carcinoma tumor cells from a patient who had responded to medroxyprogesterone acetate therapy were established in tissue culture. Cells were cultured in control medium, and in the presence of therapeutic and pharmacologic levels of medroxyprogesterone acetate. Tumor cell growth kinetics were determined by the incorporation of 3H thymidine. There was no growth inhibition effected by medroxyprogesterone acetate at therapeutic or pharmacologic levels. Therefore, the proposed salutary effect of medroxyprogesterone acetate in regression of metastatic renal cell carcinoma results from factors other than direct inhibition of renal cell carcinoma growth.

Adenocarcinoma↗
PubMed2002

Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial.

OBJECTIVE: To explore whether significant differences exist between bleeding patterns with common regimens of hormone replacement therapy using two different progestogens. METHODS: A total of 875 women in the Postmenopausal Estrogen and Progestin Interventions Trial took either placebo, conjugated equine estrogen 0.625 mg, conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg in a continuous fashion, or conjugated equine estrogen 0.625 mg daily plus either cyclical medroxyprogesterone acetate 10 mg or cyclical micronized progesterone 200 mg/day for 12 days per month. Bleeding days, amounts, and episodes were recorded in diaries and aggregated by 6-month intervals for 3 years for the 596 participants with a uterus. Any bleeding for women on continuous regimens, or more than 6 episodes of bleeding per 6-month period for cyclical regimens, was considered excess. RESULTS: Conjugated equine estrogen plus micronized progesterone cyclical was associated with fewer excess episodes of bleeding than conjugated equine estrogen plus medroxyprogesterone acetate continuous in the first 6 months. Quantities of bleeding for conjugated equine estrogen plus micronized progesterone cyclical were less than for conjugated equine estrogen plus medroxyprogesterone acetate cyclical through 30 months and for the number of bleeding days through study end. The 3-year cumulative quantities, days, and episodes of bleeding were significantly lower for conjugated equine estrogen plus micronized progesterone cyclical than for conjugated equine estrogen plus medroxyprogesterone acetate cyclical. Placebo treated women had scant bleeding and conjugated equine estrogen had modest amounts relative to the combination therapies. CONCLUSION: The bleeding measures for conjugated equine estrogen plus micronized progesterone cyclical showed consistent advantages over those for cyclical conjugated equine estrogen plus medroxyprogesterone acetate in terms of quantity, length, and episodes of bleeding. In the first 6 months, conjugated equine estrogen plus micronized progesterone cyclical had fewer excess bleeding episodes than continuous conjugated equine estrogen plus medroxyprogesterone acetate.

Aged↗
PubMed1982

Transfer of contraceptive steroids in milk of women using long-acting gestagens.

Levels of norethisterone and medroxyprogesterone acetate were measured in serum and milk of women receiving the injectable contraceptive formulations Norigest and DepoProvera, respectively, throughout complete injection intervals. In 5 of 10 women receiving Norigest, serum norethisterone levels were undetectable by 8 weeks after injection and only 2 women had detectable levels of norethisterone in milk at this time. In contrast, 8 of 10 women receiving DepoProvera had detectable levels of medroxyprogesterone acetate in both serum and milk 12 weeks after injection. The ratio of the milk:serum concentrations of norethisterone varied from 0.12 to 0.92 (mean 0.34) and for medroxyprogesterone acetate from 0.12 to 2.60 (mean 0.88). It is unlikely that these differences between the two formulations are due entirely to differences between the binding of norethisterone and medroxyprogesterone acetate to serum proteins. The area under the curve of serum steroid concentrations plotted against time was only 50% higher for women injected with DepoPovera than for those injected with Norigest but the area under the curve for milk values was 400 times higher. Assuming the infant ingests 600 ml daily, the daily intake of steroids in the first week after injection would be 0.5 to 2.4 micrograms for norethisterone and 1 to 13 micrograms for medroxyprogesterone acetate. By 8 weeks after injection, the amount of norethisterone ingested would be small but that of medroxyprogesterone acetate would still be significant.

Adult↗
PubMed1975

Progesterone for outpatient treatment of Pickwickian syndrome.

Ten patients with the Pickwickian syndrome, characterized by obesity, hypoxemia, hypercapnia, polycythemia, and cor pulmonale, underwent long-term treatment as outpatients with medroxyprogesterone acetate. Although there was no significant weight change in the group, PaO2 rose 12.6 +/- 2.7 mm Hg (SEM) from 49 +/- 2.6 mm Hg to 62 +/- 2.3 mm Hg (P less than 0.001), while PaCO2 fell 13 +/- 2.6 mm Hg from 51 +/- 1.9 mm Hg to 38 +/- 1.2 mm Hg (P less than 0.001). Hematocrit fell from 56 +/- 2.5% to 50 +/- 1.2%, a mean fall of 6% (P less than 0.01), during medroxyprogesterone acetate therapy. In the 2 patients who had cardiac catheterization before and during medroxyprogesterone acetate therapy, mean pulmonary arterial pressure fell 13 and 19 mm Hg. There were no recurrences of cor pulmonale during treatment. These effects on arterial blood gas values and clinical state were sustained during therapy. On withdrawal of medroxyprogesterone acetate during 1-month period, arterial oxygen and carbon dioxide tensions deteriorated to their previous pretreatment values. Reinstitution of medroxyprogesterone acetate caused improvement in both the oxygen and carbon dioxide tensions. We conclude that sublingual medroxyprogesterone acetate therapy is useful in the management of the Pickwickian syndrome.

Adult↗
PubMed1998

Bleeding pattern and endometrial changes during continuous combined hormone replacement therapy. The Ogen/Provera Study Group.

OBJECTIVE: To establish the optimum oral daily dose of micronized medroxyprogesterone acetate, given in combination with a fixed oral dose of estrone (E1) sulfate as hormone replacement therapy, that provides endometrial protection and induces cessation of vaginal bleeding. METHODS: This multicenter, randomized, double-blind study was conducted for 2 years. Five hundred sixty-eight postmenopausal women were randomized to take E1 sulfate 1.25 mg daily and one of three doses of medroxyprogesterone acetate (2.5, 5, or 10 mg) daily. Any vaginal bleeding was recorded by patients in a daily diary, and endometrial biopsies were performed at entry into the study and at 3, 12, and 24 months. RESULTS: Forty-two percent of all women reported some bleeding at month 3 of therapy. However, by month 6, 76.5, 80.1, and 80.9% of women were amenorrheic in the 2.5-, 5-, and 10-mg medroxyprogesterone acetate groups, respectively. Over time, the percentage of women with no bleeding increased in each group, and by 24 months 91.5, 89.9, and 94.3% were amenorrheic in the 2.5- and 10-mg medroxyprogesterone acetate groups, respectively. Approximately 10% of women continue to have some bleeding, regardless of the dose of medroxyprogesterone acetate. There were no statistically significant differences in the number of women with bleeding at any time point between the three groups. There were no cases of endometrial hyperplasia reported in the study population over the 2 years. CONCLUSION: All three studied doses of medroxyprogesterone acetate, given in combination with 1.25 mg of E1 sulfate, provide adequate endometrial protection and render approximately 80% of women amenorrheic by 6 months of therapy.

Adult↗
PubMed2004

Effects of hormonal contraception on bone mineral density after 24 months of use.

OBJECTIVE: To measure the effect of 24 months of depot medroxyprogesterone acetate use on bone mineral density compared with oral contraception (pills) and nonhormonal contraception. METHODS: Women aged 18-33 years self-selected oral contraception, depot medroxyprogesterone acetate, or nonhormonal contraception (controls). Those selecting pills were randomized to formulations containing either 35 microg ethinyl estradiol and norethindrone or 30 microg ethinyl estradiol and desogestrel. Controls were frequency matched on age and race/ethnicity to hormonal contraception users. Dual-energy X-ray absorptiometry of the lumbar spine (L1-L4) was performed at baseline, 12 months, and 24 months. Percent change in bone mineral density was analyzed by using analysis of covariance, adjusting for age, race/ethnicity, weight-bearing exercise, calcium intake, smoking status, and body mass index. RESULTS: Of the 191 women making up the final sample, 86 used pills, 47 used depot medroxyprogesterone acetate, and 58 used nonhormonal contraception. Women using depot medroxyprogesterone acetate for 24 months experienced, on average, a 5.7% loss in bone mineral density, with a 3.2% loss occurring between months 12 and 24. On average, users of desogestrel pills experienced a 2.6% loss in bone mineral density after 24 months. Bonferroni-adjusted pairwise comparisons demonstrated that bone mineral density changes from baseline to 24 months among depot medroxyprogesterone acetate users differed significantly from changes experienced by either of the pill groups or the control group. Changes in bone mineral density among users of either pill did not significantly differ from each other or from controls. CONCLUSION: Loss of bone mineral density associated with depot medroxyprogesterone acetate use appears to be linear during the first 2 years of use. Shifts in bone mineral density among pill users were not significant when compared with controls.

Adolescent↗
PubMed1994

Cyclic hormone replacement therapy using quarterly progestin.

OBJECTIVES: To determine whether cyclic progestin, when part of postmenopausal hormone replacement therapy, can be used quarterly instead of monthly without increasing the risk of endometrial hyperplasia. In addition, we determined whether this hormone replacement therapy regimen produces an acceptable menstrual pattern. METHODS: The subjects were 214 postmenopausal women, mean (+/- standard deviation) age 56.2 +/- 5.4 years, who had regularly used hormone replacement therapy (consisting of Premarin 0.625 mg/day with monthly cyclic medroxyprogesterone, 5 or 10 mg) for a mean of 5.4 +/- 4.5 years (minimum 1 year). The study intervention consisted of changing the subjects' treatment from the usual monthly progestin to four 3-month (ie, quarterly) cycles of medroxyprogesterone, 10 mg/day for 14 days. Endometrial histology was evaluated by doing endometrial biopsies at study outset and after 1 year. Scheduled and unscheduled vaginal bleeding was reported in daily diaries. RESULTS: Endometrial hyperplasia was found in 1.5% of 199 women completing follow-up, a rate similar to the 0.9% prevalence found at baseline. Compared with monthly medroxyprogesterone, quarterly medroxyprogesterone resulted in longer menses (7.7 +/- 2.9 versus 5.4 +/- 2.0 days) and more reports of heavy menses (31.1 versus 8.0%) and unscheduled bleeding (15.5 versus 6.8%). Despite these problems, women preferred the quarterly regimen by nearly four to one. CONCLUSIONS: In a 1-year trial, quarterly medroxyprogesterone appeared as safe as monthly medroxyprogesterone and was preferred by most women. This schedule may be useful for women seeking relief from monthly use of progestin and monthly menses.

Adult↗
PubMed1985

Hospitalizations among black women using contraceptives.

We analyzed hospitalizations among 26,507 young black women who attended a large metropolitan family planning clinic between 1968 and 1976. Age-adjusted hospitalization rates were compared for women using oral contraceptives, intrauterine contraceptive devices, and depot medroxyprogesterone acetate. Overall, intrauterine contraceptive device and depot medroxyprogesterone acetate users were hospitalized at about the same rate, while women using oral contraceptives were hospitalized 30% less often. The oral contraceptive users were not hospitalized at a higher rate for circulatory disease. Compared to women using intrauterine contraceptive devices, users of oral contraceptives and depot medroxyprogesterone acetate were less likely to be hospitalized for benign breast disease (rate ratios = 0.5 and 0.2, respectively, with 95% confidence limits of 0.3 to 0.7 and 0.1 to 0.5) and for pelvic inflammatory disease. Women were four times as likely to be using depot medroxyprogesterone acetate when they were hospitalized with carcinoma in situ of the cervix, but depot medroxyprogesterone acetate users with at least 3 years of use were less likely to be hospitalized for carcinoma in situ than comparable groups of oral contraceptive and intrauterine contraceptive device users.

Adolescent↗
PubMed1982

The effect of sex steroids on radioimmunoassayable plasma somatomedin C concentrations.

While the effect of sex steroids on growth is well known, their effects on somatomedin C, a mediator of growth, are unclear. To investigate the effect of sex steroids on somatomedin C (Sm-C) concentrations, Sm-C was measured in adults receiving pharmacological doses of various sex steroids (estrogens, testosterone, and medroxyprogesterone acetate). Testosterone therapy had no effect on the somatomedin C concentration. Although both estrogen and medroxyprogesterone acetate therapy reduced the plasma testosterone concentration into the normal female range, they had different effects on Sm-C concentrations. Estrogen therapy produced no detectable change in the Sm-C concentration; medroxyprogesterone acetate caused an increase in the plasma somatomedin C concentration (P less than 0.001). Since medroxyprogesterone acetate also does not increase the serum GH concentration, other mechanisms by which medroxyprogesterone acetate stimulates Sm-C production are discussed.

Adult↗
PubMed1995

Metabolic parameter, bleeding, and weight changes in U.S. women using progestin only contraceptives.

Our objective was to determine the effect of progestin-only contraceptives on metabolic parameters, bleeding patterns, and weight changes during the first year of use. Seventy-one women (> 95% Caucasian), who were advised regarding contraception alternatives, self-selected levonorgestrel implants (n = 44), depo-medroxyprogesterone acetate (n = 22), or oral norethindrone (n = 5). One year later, 11 levonorgestrel implant and five depomedroxyprogesterone acetate patients were randomly selected to compare (pre- and post-progestin use) levels of cholesterol, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), apolipoproteins A-1 and B-100, bilirubin, and sex hormone binding globulin. Monthly bleeding and spotting records were kept in each group. Body weights were also monitored in each group. No statistically significant differences in metabolic parameters were found between pre- and post-progestin use in the levonorgestrel implant and depo-medroxyprogesterone acetate groups. Continued bleeding patterns were more prominent in the levonorgestrel implant and oral norethindrone groups than in patients receiving depo-medroxyprogesterone acetate. No significant weight gain was detected in any group. No changes in metabolic parameters or weight were noted over the one year of use of levonorgestrel implants or depo-medroxyprogesterone acetate. Depo-medroxyprogesterone acetate had the highest incidence of amenorrhea.

Administration, Oral↗
PubMed1995

Progesterone antagonist RU 486 has bone-sparing effects in ovariectomized rats.

We demonstrated previously that progesterone prevents ovariectomy-induced bone loss. RU 486 is a synthetic steroid with antiprogesterone activities in reproductive tissue. We used 12-week-old rats to evaluate effects of RU 486 in sham-operated rats and to compare medroxyprogesterone (MPA), RU 486, and medroxyprogesterone plus RU 486 combined treatment in ovariectomized rats. Ovariectomized rats were treated with MPA (60 mg/kg intramuscularly), RU 486 (10 mg/kg/day subcutaneously every 4 days), both, or vehicle. Sham-operated rats were treated with similar doses of RU 486 or vehicle. After 4 weeks of treatment the rats were sacrificed and bone histomorphometry was performed on proximal tibial metaphysis. Trabecular bone volume was lower (33.9 +/- 1.5% vs. 46.3 +/- 1.4%) and bone turnover was higher in ovariectomized than in sham-operated rats. The fraction of trabecular bone in OVX rats treated with MPA, RU 486, or both were 41.6 +/- 2.5%, 44.8 +/- 2.8%, and 38.4 +/- 1.4%, respectively. Medroxyprogesterone treatment tended to preserve bone mass by inhibiting the increased resorption indices while maintaining higher formation rates seen in ovariectomized rats. The effects of RU 486 were similar to those of medroxyprogesterone, suggesting an agonist-like effect. Medroxyprogesterone effects were attenuated when it was combined with RU 486, suggesting that RU 486 acted as a partial antagonist in the presence of exogenous progesterone. Bone parameters were less affected in sham-operated RU 486-treated rats, and there was no significant change in bone volume (43.2 +/- 1.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1996

Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal cynomolgus macaques.

OBJECTIVE: Our purpose was to define the proliferative response and receptor status in the mammary glands of surgically postmenopausal macaques given hormone replacement therapy, equivalent for monkeys to that given women. STUDY DESIGN: Surgically postmenopausal adult female cynomolgus macaques (Macaca fascicularis) were given either no treatment (n = 26), conjugated equine estrogens (n = 22), or combined therapy with conjugated equine estrogens and medroxyprogesterone acetate (n = 21). Drugs were administered in the diet, at doses equivalent on a caloric basis to 0.625 mg per woman per day for conjugated equine estrogens and 2.5 mg per woman per day for medroxyprogesterone acetate, for 30 months. Mammary gland proliferation was assessed subjectively and by morphometric and stereologic means. Estrogen receptor and progesterone receptor content and proliferation were studied by immunohistochemistry. RESULTS: In this model combined therapy with conjugated equine estrogens and medroxyprogesterone acetate induced greater proliferation than did conjugated equine estrogens alone. The percentage of estrogen receptor-positive cells was decreased in the conjugated equine estrogens plus medroxyprogesterone acetate group. The percentage of progesterone receptor-positive cells was increased by treatment with conjugated equine estrogens alone. CONCLUSION: These results indicate a proliferative response of mammary gland epithelium to therapy with conjugated equine estrogens plus medroxyprogesterone acetate in postmenopausal macaques. The clinical implication of this finding may be a greater risk for development of breast neoplasms in women receiving combined hormone replacement therapy.

Animals↗
PubMed2000

Negative mood changes during hormone replacement therapy: a comparison between two progestogens.

OBJECTIVE: The aim of this study was to compare side effects of medroxyprogesterone acetate and norethindrone acetate during postmenopausal hormone replacement therapy in women with and without a history of premenstrual syndrome. STUDY DESIGN: Fifty-one postmenopausal women were randomly selected in a double-blind crossover study. The women received 2 mg of estradiol continuously during five 28-day cycles and 10 mg of medroxyprogesterone or 1 mg of norethindrone sequentially for 12 days of each cycle. Daily symptom rating scales were kept. RESULTS: The women showed cyclic changes, with negative mood and physical symptoms culminating during the late progestogen phase and positive mood during the estrogen-only phase. Symptoms declined with time but remained after 5 months. Women with a history of premenstrual syndrome responded strongly to both progestogens. Medroxyprogesterone acetate induced less negative and more positive mood symptoms than norethindrone in women with no history of premenstrual syndrome. In both groups medroxyprogesterone caused more physical symptoms than norethindrone. CONCLUSION: The addition of medroxyprogesterone to estrogen is preferable to norethindrone with respect to mood symptoms in women without a history of premenstrual syndrome.

Affect↗
PubMed2001

Regulation of plasminogen activator inhibitor 1 expression by interaction of epidermal growth factor with progestin during decidualization of human endometrial stromal cells.

OBJECTIVE: During human pregnancy implantation, trophoblasts invade maternal blood vessels in a process that risks hemorrhage. Previous studies have demonstrated enhanced expression of type 1 plasminogen activator inhibitor, the primary inhibitor of fibrinolysis, during progestin-induced decidualization of estradiol-primed human endometrial stromal cells in vivo and in vitro. Decidual cell-expressed plasminogen activator inhibitor 1 is appropriately positioned to avert implantational hemorrhage. Because of the absence of estrogen or progesterone response elements from the plasminogen activator inhibitor 1 gene promoter, I posited that epidermal growth factor mediates these steroid effects and that expression of epidermal growth factor receptor in human endometrial stromal cells is under ovarian steroid control. STUDY DESIGN: Confluent human endometrial stromal cells were exposed to vehicle control or to either estradiol (10(-8) mol/L) or medroxyprogesterone acetate (10(-7) mol/L), or both, with or without growth factors. After 40 hours the cultures were analyzed for plasminogen activator inhibitor 1 protein and messenger ribonucleic acid expressions. Immunostaining for epidermal growth factor receptor was carried out in sections of cycling and gestational endometrial tissues. RESULTS: In the absence of steroids, epidermal growth factor did not alter plasminogen activator inhibitor 1 expression. In the absence of epidermal growth factor, estradiol and medroxyprogesterone acetate enhanced human endometrial stromal cell-secreted plasminogen activator inhibitor 1 protein levels 8-fold (n = 12; P <.001), whereas estradiol alone had no effect. Marked synergistic increases in plasminogen activator inhibitor 1 levels were elicited when epidermal growth factor was added with estradiol and medroxyprogesterone acetate (n = 12; 65-fold; P <.0001). Both transforming growth factor alpha and epidermal growth factor, which act through epidermal growth factor receptor, increased steady-state plasminogen activator inhibitor 1 messenger ribonucleic acid levels several-fold when added with estradiol and medroxyprogesterone acetate. In contrast, transforming growth factor beta, which does not activate epidermal growth factor receptor, did not elevate plasminogen activator inhibitor 1 messenger ribonucleic acid or protein levels whether added alone or with estradiol and medroxyprogesterone acetate. In correspondence with these in vitro observations, immunostaining for epidermal growth factor receptor was increased in human endometrial stromal cells undergoing decidualization in sections of secretory phase and first-trimester endometrial tissue. CONCLUSIONS: Taken together, these in vitro and in vivo results indicate that both epidermal growth factor and progesterone receptors are required for maximal plasminogen activator inhibitor 1 expression by human endometrial stromal cells.

Blotting, Northern↗
PubMed1993

Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin's disease.

Ovarian damage, with consequent permanent infertility, is one of the more common side-effects which occurs during chemotherapeutic treatment of patients affected by Hodgkin's disease. This damage is morphologically represented by a marked loss of primordial and primary follicles. The administration of contraceptive drugs before starting chemotherapy enhances survival of a greater number of ovarian follicles, as revealed by morphometric analyses, nevertheless, total ovarian protection is not assured. This study evaluated the number and the morphology of ovarian follicles, by means of transmission electron microscopy, in patients with Hodgkin's disease treated with multi-drug chemotherapeutic protocols following the administration of medroxyprogesterone acetate. Ovarian biopsies were performed prior to any pharmacological treatment, after medroxyprogesterone therapy, and after this therapy plus chemotherapy. Particular attention was given to the ultrastructure of primordial follicles. After morphometric evaluation, primordial follicles were numerous in controls and medroxyprogesterone therapy (28.55 +/- 6.59/mm3 of ovarian cortex). After chemotherapy and medroxyprogesterone acetate, the number of follicles was slightly reduced (19.37 +/- 3.41/mm3 of ovarian cortex) in contrast to the dramatic loss usually observed when protection is not given, although more follicles were atretic. Medroxyprogesterone may protect follicles only from acute, toxic effects of chemotherapy, which dramatically reduce their number and lead to sterility. Nevertheless, the quality of follicles is still impaired, and many undergo atresia, resulting in a shortened fertility period.

Adult↗
PubMed2006

Activation of nitric oxide synthesis in human endothelial cells using nomegestrol acetate.

OBJECTIVE: Recent clinical trials indicate that synthetic progestins may be unexpectedly relevant for the development of cardiovascular disease. The aim of this study was to establish whether nomegestrol acetate induces signaling events in human endothelial cells that differ from those of other progestins, such as natural progesterone or medroxyprogesterone acetate. METHODS: We used human endothelial cells to study the action of nomegestrol acetate (either alone or in the presence of estradiol [E2]) on the synthesis of nitric oxide (NO) and on the activity or expression of endothelial nitric oxide synthase (eNOS). We compared the effects of nomegestrol acetate with those of progesterone or medroxyprogesterone acetate. In addition, we characterized the signaling events recruited by these compounds. RESULTS: Progesterone and nomegestrol acetate increase NO synthesis by transcriptional and nontranscriptional mechanisms, whereas medroxyprogesterone acetate lacks such effects. When used together with physiological E2 concentrations, progesterone and nomegestrol acetate do not interfere with (or even enhance) E2 effects, whereas medroxyprogesterone acetate impairs E2 signaling. A marked difference in the recruitment of mitogen-activated protein kinase and phosphatidylinositol-3 kinase explains the divergent effects of the three gestagens. CONCLUSION: Our findings show significant differences in the signal transduction pathways recruited by progesterone, nomegestrol acetate, and medroxyprogesterone acetate in human endothelial cells that may have relevant clinical implications.

Cells, Cultured↗
PubMed2001

Overview of the relationship between use of progestogen-only contraceptives and bone mineral density.

OBJECTIVES: To summarise the available epidemiological evidence regarding the relationship between the use of progestogen-only contraceptives and bone mineral density. DESIGN AND METHODS: Overview of the published epidemiological literature. RESULTS: Overall, 17 studies of the use of progestogen-only contraceptives and bone mineral density were identified, involving 1529 women exposed to progestogen-only contraceptives and 2086 controls. Sixty-eight percent of the data relate to the effects of use of depot medroxyprogesterone acetate. Average bone mineral density was reduced in current users of depot medroxyprogesterone acetate compared with non-users, although density in users was within one standard deviation of the mean in non-users. There was significant heterogeneity between the results of different studies (P < 0.0001). The reduction in bone mineral density appeared to be greater at the lumbar spine, femoral neck and ultradistal forearm than at the midshaft of the ulna. Studies involving women with a longer average duration of use of depot medroxyprogesterone acetate displayed greater reductions in bone mineral density compared with studies of women with shorter durations of use. Based on limited data, no difference in bone mineral density was observed between former and never users of depot medroxyprogesterone acetate. Results regarding the effect of levonorgestrel implants were conflicting. Studies of progestogen-only oral contraceptives and the progesterone vaginal ring were small and restricted to lactating women. CONCLUSIONS: Women currently using depot medroxyprogesterone acetate have a lower average bone mineral density than non-users. The magnitude of this effect is uncertain but appears to be greater with longer durations of use.

Adolescent↗