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PubMed1997

Differential effects of hormone-replacement therapy on endogenous nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate.

Increased incidence of cardiovascular disease in postmenopausal women (PMW) is accompanied by ovarian dysfunction; hormone replacement therapy (HRT) can have cardioprotective effects. Because hypertension and atherosclerosis are associated with impaired release of endothelium-derived nitric oxide (NO) and increased levels of low-density lipoproteins (LDL), we investigated whether HRT augments NO release, and whether these increases are accompanied by a decrease in LDL levels in PMW. We determined serum nitrite/ nitrate (NO2-/NO3-) and LDL levels at baseline (before initiation of HRT) and during the 6th and 12th months of the study. The PMW (n = 26) received continuous oral administration of estradiol valerate (Progynova, 2 mg daily) for 21 days supplemented with either oral cyproterone acetate (CPA; 1 mg; n = 11) or medroxyprogesterone acetate (MPA; 5 mg; n = 15) on days 12-21 of each treatment cycle. Blood samples in the PMW receiving HRT were collected at times while the subjects were taking estradiol valerate alone and estradiol valerate plus CPA or MPA. Compared with the samples collected at baseline, serum NO2-/NO3- levels increased significantly from 20.1 +/- 1.58 mumol/L at baseline to 30 +/- 3.7 mumol/L (P < 0.01) in samples collected after 12 months of HRT while the PMW were not taking progestins (CPA or MPA), and to 25.4 +/- 2 mumol/L (P < 0.05) when all the samples, regardless of the treatment with CPA or MPA, were included in the analysis. Moreover, > 30% increase in serum NO2-/NO3- levels were observed only in 13 (responders) out of 26 PMW substituted with estradiol valerate, suggesting that estradiol may improve endogenous NO synthesis in a differential fashion. Compared with baseline, no significant increases in serum NO2-/NO3- were observed in samples collected while the estradiol-treated responders were taking either CPA or MPA. In contrast to NO2-/NO3- serum LDL levels were significantly reduced in samples collected after 12 months of HRT (P < 0.05 vs. baseline). Furthermore, levels of NO2-/NO3 showed a significant negative correlation with the levels of LDL (r2 = 0.17; P < 0.05) in the responders but not in nonresponders. These results indicate that oral administration of estradiol valerate in PMW for HRT increases circulating NO levels, an effect that may contribute to the cardioprotective effects of HRT in PMW. In addition, our data suggests but does not prove that concomitant administration of a progestin may attenuate the beneficial effects of estrogen replacement therapy with regard to NO release. Finally, our data provides evidence for the existence of responders and nonresponders to postmenopausal estrogen treatment with respect to improvement of endogenous NO levels, suggesting that a significant number, but not all, of the hormonally substituted PMW profit fully from the beneficial properties of a HRT.

Estradiol↗
PubMed1999

Dissociative glucocorticoid activity of medroxyprogesterone acetate in normal human lymphocytes.

The immunosuppressive effects of glucocorticoids (GC) have led to their wide application in the treatment of inflammatory and autoimmune states. However, long term GC treatment is associated with severe side-effects. The development of agents displaying a more favorable ratio of wanted and unwanted GC effects, is, therefore, a major goal of pharmacological and clinical research. In this study, the progesterone receptor agonist medroxyprogesterone acetate (MPA), which also binds to the glucocorticoid receptor (GR), was tested with regard to its immunosuppressive properties. Using a recently established electroporation protocol, we show that MPA (but not progesterone) can suppress a human interleukin-2 (IL-2) promoter-luciferase construct to the same extent as the synthetic GC dexamethasone in normal human lymphocytes. MPA also markedly suppressed IL-2 (as well as IL-1 and IL-6) release, as assessed by specific enzyme-linked immunosorbent assays. In contrast, a highly dexamethasone-inducible glucocorticoid response element-driven promoter construct was only marginally stimulated by MPA in both normal human lymphocytes and HeLa cells. RT-PCR and Western blot analysis of normal human lymphocytes revealed that they do not express progesterone receptor messenger ribonucleic acid and protein, respectively. In contrast, the GR protein was clearly detectable in all samples and was shown to mediate the effects of MPA in transfected Jurkat T lymphoma cells. Our data indicate that 1) MPA can transrepress the human IL-2 gene in normal human lymphocytes in the absence of significant trans-activation; and 2) this effect is mediated by GR. Because of its dissociative GC activity, MPA is a highly promising substance for the treatment of inflammatory/autoimmune states.

Blotting, Western↗
PubMed1999

Medroxyprogesterone acetate and dexamethasone are competitive inhibitors of different human steroidogenic enzymes.

Medroxyprogesterone acetate (MPA), a widely used progestin, can suppress the hypothalamic-pituitary-gonadal axis but can also directly inhibit gonadal steroidogenesis; the success of MPA as a treatment for gonadotropin-independent sexual precocity derives from its direct action on steroidogenic tissues. Dexamethasone, a widely used glucocorticoid, can suppress the hypothalamic-pituitary-adrenal axis, but its potential effect directly on the adrenal is unclear. Previous reports suggested that these two drugs may act on the initial steps in the rodent steroidogenic pathway; therefore, we investigated their abilities to inhibit the first three human enzymes in steroidogenesis: the cholesterol side-chain cleavage enzyme (P450scc), the 17alpha-hydroxylase/17,20-lyase (P450c17), and type II 3beta-hydroxysteroid dehydrogenase/isomerase (3betaHSDII). We found no effect of either drug on P450scc in intact human choriocarcinoma JEG-3 cells. Using microsomes from yeast expressing human P450c17 or microsomes from human adrenals, we found that dexamethasone inhibited P450c17 with a Ki of 87 micromol/L, which is about 1000 times higher than typical therapeutic concentrations, but that MPA has no detectable action on P450c17. Using microsomes from yeast expressing human 3betaHSDII, we found that this enzyme has indistinguishable apparent Km values of 5.2-5.5 micromol/L and similar maximum velocities of 0.34-0.56 pmol steroid/min x microg microsomal protein for the three principal endogenous substrates, pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone. In this system, MPA inhibited 3betaHSDII with a Ki of 3.0 micromol/L, which is near concentrations achieved by high therapeutic doses of 5-20 mg MPA/kg x day. These data establish the mechanism of action of MPA as an inhibitor of human steroidogenesis, and are in contrast with the results of earlier studies indicating that MPA inhibited both P450c17 and 3betaHSD in rat Leydig cells. These studies establish the "humanized yeast" system as a model for studying the actions of drugs on human steroidogenic enzymes and suggest that 3betaHSDII may be an appropriate target for pharmacological interventions in human disorders characterized by androgen excess or sex steroid dependency.

Animals↗
PubMed2002

Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men.

Testosterone (T) treatment suppresses gonadotropin levels and sperm counts in normal men, but the addition of a progestin may improve the efficacy of hormonal contraception. This study aimed to investigate the speed and extent of suppression of testicular germ cell number induced by T plus or minus progestin treatment and correlate these changes with serum gonadotropins and inhibin B levels, testicular androgens, and sperm output. Thirty normal fertile men (31-46 yr) received either testosterone enanthate (TE, 200 mg im weekly) alone or TE plus depot medroxyprogesterone acetate (DMPA, 300 mg im once) for 2, 6, or 12 wk (n = 5 per group) before vasectomy and testis biopsy. Five men (controls) proceeded directly to surgery. The inclusion of DMPA led to a more rapid fall in serum FSH/LH levels (time to 10% baseline: FSH; 12.6 +/- 2.6 vs. 7.9 +/- 1.4 d; LH, 9.9 +/- 3.4 vs. 3.4 +/- 1.7 d, TE vs. TE+DMPA, respectively, mean +/- SD, both P < 0.0001), yet the mean time to reach a sperm count 10% of baseline was not different (23.7 +/- 7.3 vs. 25.3 +/- 13.9 d, NS). The maximum extent of FSH/LH suppression was identical at 12 wk (mean serum FSH 1.2 and 1.6%, and mean LH 0.3 and 0.2% of baseline: TE vs. TE+ DMPA, respectively) as was sperm count suppression (5 of 5 and 4 of 5 men, respectively, with sperm counts < or =0.1 x 10(6)/ml). Serum inhibin decreased to 55% control at 12 wk in the TE+DMPA group (P < 0.05) but was unchanged by TE treatment (86% control, NS). Testicular T levels declined to approximately 2% of control levels, but testicular dihydrotestosterone and 5alpha-androstane-3alpha,17beta-diol (Adiol) levels were not different to control. Germ cell numbers as determined by stereological methods did not differ between TE and TE+DMPA except at 2 wk when type B spermatogonia and early spermatocytes were significantly lower in the TE+DMPA group (P < 0.05). In all groups, a marked inhibition of Apale-->B spermatogonial maturation was seen along with a striking inhibition of spermiation. We conclude that: 1) the addition of DMPA hastens the onset of FSH/LH suppression, correlating with a more rapid impairment of spermatogonial development, but in the longer term, neither germ cell number nor sperm count differed; 2) testicular dihydrotestosterone and Adiol levels are maintained during FSH/LH suppression despite markedly reduced T levels suggesting up-regulation of testicular 5alpha-reductase activity; and 3) spermatogonial inhibition is a consistent feature, but spermiation inhibition is also striking and is an important determinant of sperm output.

Adult↗
PubMed1993

Enhanced c-jun activity alters responsiveness to medroxyprogesterone acetate in Ishikawa human endometrial carcinoma cells.

The involvement of altered c-jun activity in medroxyprogesterone acetate (MPA)-induced growth responses in human endometrial carcinoma cells is examined in this paper. Under conditions of MPA-induced growth inhibition, c-jun mRNA and protein levels are decreased in Ishikawa cells. This decrease is accompanied by an overall decrease in endogenous AP-1 activity in these cells. Only a transient decrease in c-jun mRNA level without any effect on endogenous AP-1 activity is seen in HEC-50 human endometrial carcinoma cells after MPA treatment. Increased expression and activity of c-jun was achieved in Ishikawa cells by transient transfection of Rous sarcoma virus (RSV)-c-jun alone or RSV-c-jun plus AP-1 binding sites (5x-4-beta-phorobol 12-myristate 13-acetate response element-thymidine kinase-chloramphenicol acetyltransferase), respectively. These treatments were accompanied by an increase in cell numbers due to MPA treatment in Ishikawa cells. In contrast, MPA treatment of mock-transfected, RSV-jun-B-transfected, or 5x-4 beta-phorbol 12-myristate 13-acetate response element-thymidine kinase-chloramphenicol acetyltransferase alone transfected Ishikawa cells resulted in the expected decrease in cell numbers. The data presented in this paper are consistent with the hypothesis that altered c-jun activity in a target cell can alter proliferative responsiveness to MPA and suggest that such a mechanism may be associated with resistance to hormonal manipulative therapies used in the treatment of both human breast and endometrial cancer.

Carcinoma↗
PubMed2006

Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).

We synthesized 9alpha-fluoromedroxyprogesterone acetate (FMPA) in order to test whether it is a more potent anti-angiogenic agent than medroxyprogesterone acetate (MPA), which has been widely used as a therapeutic agent for breast and endometrium cancers. FMPA was previously synthesized in 10 steps (total yield: 1%). An efficient synthesis of FMPA has been achieved in 6 steps (total yield: 12%). We examined the anti-tumor effect of FMPA, complexed with dimethyl-beta-cyclodextrin (DM-beta-CyD), on rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA). FMPA showed great anti-tumor effect on DMBA-induced rat mammary carcinomas.

Administration, Oral↗
PubMed2003

Comparison of the effect of progesterone, medroxyprogesterone acetate and norethisterone on the proliferation of human breast cancer cells.

OBJECTIVE: To investigate in vitro the influence of the three most used progestogens in continuous combined HRT on cell proliferation of the human breast cancer cell line MCF-7. STUDY DESIGN: Progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) were investigated in the range of 0.01 nM to 10 microM alone and in combination with 10 nM oestradiol. Cell proliferation was measured after seven days using the ATP-chemosensitivity test. RESULTS: P alone reduced cell proliferation by 20 and 40% at 10(-7) and 10(-5) M. MPA and NET displayed a significant inhibition of cell proliferation between 20 and 25% for MPA and 23 and 41% for NET over the whole concentration range tested. The effect was greatest at 10(-7) M for MPA and at 10(-9) M for NET. In combination with oestradiol, P still significantly reduced cell proliferation, the values being between 12 and 61%. For MPA too an inhibitory effect between 20 and 40% was found, whereas for NET the values were between 23 and 38%. CONCLUSIONS: Our in vitro results indicate that the influence on breast cancer risk using HRT in postmenopausal women may depend on the type of progestogen used as well as on the regimen applied. However, the inhibitory in vitro net effect of the progestogens at clinically relevant dosages is rather minimal and it remains uncertain as to whether progestogens generally may reduce breast cancer risk in long-term treatment. Further clinical trials are urgently required to determine the appropriate choice - if any - of progestogen to complement HRT.

Breast↗
PubMed1994

Medroxyprogesterone acetate and ethanol-induced exacerbation of obstructive sleep apnea.

OBJECTIVE: To determine if medroxyprogesterone acetate (MPA) can block the ethanol-induced worsening of obstructive sleep apnea. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial with 1 week treatment periods. SETTING: A university-based pulmonary sleep laboratory. PATIENTS: Fourteen patients with previously diagnosed obstructive sleep apnea not currently receiving any form of therapy for the disorder. Eight patients completed the entire protocol. INTERVENTIONS: Baseline overnight polysomnography was performed. On the second study night, subjects ingested 1 ml/kg body weight 50 percent ethanol prior to repeat overnight polysomnography. If sleep apnea worsened, subjects then received either MPA (20 mg by mouth, three times a day) or placebo for 7 days then underwent repeat polysomnography with the same ethanol dose. A washout period followed, then, the other drug was taken, followed again by polysomnography with antecedent ethanol ingestion. MEASUREMENTS AND RESULTS: Apnea-hypopnea indices (AHI) increased from 9.6 +/- 5.3 events/h (baseline) to 20.2 +/- 16.0 events/h on the ethanol night (p = 0.03). Low oxygen saturation (SaO2) fell to 79.2 +/- 5.1 percent on the ethanol night compared to baseline, 85.0 +/- 3.7 percent (p < 0.01). MPA improved AHI, nonrapid eye movement AHI, low SaO2, mean saturation nadir, number of desaturations between 80 and 90 percent, and the mean event desaturation when compared with the ethanol alone night. All these parameters were likewise improved when compared with placebo, although only the mean saturation nadir showed statistical significance. These findings were unchanged when also examined for the initial 3 hours of study. CONCLUSIONS: In obstructive sleep apnea patients whose disease is made worse by ethanol ingestion, MPA appears to improve oxygenation during obstructive events but not to improve their number or length.

Adult↗
PubMed1999

Respiratory insufficiency in postmenopausal women: sustained improvement of gas exchange with short-term medroxyprogesterone acetate.

STUDY OBJECTIVES: The degree and duration of respiratory stimulation of medroxyprogesterone acetate (MPA) in postmenopausal women. DESIGN: A placebo-controlled single-blind trial. SETTING: University hospital in Turku, Finland. PATIENTS: Fourteen postmenopausal women with permanent or previous episodic hypercapnic or hypoxemic respiratory failure. INTERVENTIONS: A 12-week trial including 14-day treatment periods with placebo and MPA (60 mg daily) and a 6-week follow-up. RESULTS: Thirteen of 14 patients completed the trial. The mean (+/- SD) PaCO2 at baseline was 42.8+/-4.5 mm Hg and the mean PaO2 was 71.2+/-9.0 mm Hg. The average reduction of PaCO2 was 6.3 mm Hg (14.7%, p < 0.001) on MPA and 3.0 mm Hg (6.1%, p = 0.001) after a 3-week washout. At 6 weeks after MPA, the PaCO2 had returned to baseline. The mean changes in PaO2 (+6.0+/-18.0 mm Hg on MPA and +3.8+/-22.5 mm Hg after a 3-week washout) were not significant. The PaO2/PaCO2 ratio increased, and bicarbonate and base excess decreased (p < 0.001) on MPA but not during washout. The systolic BP did not change on MPA but decreased on average 14.8+/-15.0 mm Hg (p = 0.016) after a 3-week washout. The diastolic BP remained unchanged. CONCLUSIONS: Our results suggest that postmenopausal women with chronic respiratory insufficiency consistently improve on MPA at a dose of 60 mg daily for 14 days. Lower PaCO2 is sustained for at least 3 weeks after cessation of MPA. The sustained effects in gas exchange and favorable after-effects in BP warrant further studies into the therapeutic efficacy and possible benefits of MPA pulse therapy.

Blood Gas Analysis↗
PubMed2003

Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD.

BACKGROUND: Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD. DESIGN AND METHODS: The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P(0.1)) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV(1), 33 +/- 4% predicted [mean +/- SEM]). RESULTS: Daytime PaCO(2) decreased from 47.3 +/- 0.8 mm Hg (placebo) to 42.0 +/- 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 +/- 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO(2) improved with acetazolamide from 65.2 +/- 2.3 to 75.0 +/- 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 +/- 2.3 to 35.3 +/- 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 +/- 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 +/- 10.7% to 16.3 +/- 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 +/- 0.7 to 10.8 +/- 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 +/- 0.05 to - 0.4 +/- 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 +/- 0.1 L/min/% during MPA (p < 0.05). The hypoxic P(0.1) response improved with acetazolamide treatment from - 0.05 +/- 0.008 to - 0.15 +/- 0.02 mm Hg/% (p < 0.05). CONCLUSIONS: This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation.

Acetazolamide↗
PubMed1983

Medroxyprogesterone acetate and COPD. Effect on breathing and oxygenation in sleeping and awake patients.

The effects of oral medroxyprogesterone acetate (MPA) (20 mg three times daily) were assessed on sleep-disordered breathing and on arterial blood gas levels in awake patients with chronic obstructive pulmonary disease (COPD). Seventeen men and two women (mean baseline PaO2, 65 mm Hg; PaCO2, 41 mm Hg; and FEV1/FVC ratio, 48 percent) participated in a double-blind, placebo-controlled, randomized study. After an initial night of polysomnography and daytime arterial blood gas analysis, the patients were randomized to receive either MPA or an identical placebo for one month; the studies were then repeated. The alternate compound was given for an additional month, and the studies were performed a third time. MPA in awake patients was associated with an increased mean PaO2 value, reduced PaCO2, and increased pH. Although there was no significant change in the number of episodes of sleep apnea, hypopnea, desaturation, or the minimal saturation, MPA marginally decreased the number of minutes of total sleep time when oxygen saturation was less than 90 percent (p = .06). In conclusion, MPA improves oxygenation and CO2 elimination and increases the pH in awake patients with COPD, but during sleep, does not significantly affect disordered breathing and only marginally improves desaturation.

Acid-Base Equilibrium↗
PubMed2002

Regulation of human endometrial transforming growth factor beta1 and beta3 isoforms through menstrual cycle and medroxyprogesterone acetate treatment.

The progesterone-induced differentiation of endometrial tissue from proliferative into secretory and decidua seems to be modulated by locally produced hormones and cytokines. Transforming growth factor beta (TGFbeta). a cytokine produced by endometrial cells, has been shown to modulate endometrial cell proliferation in vitro. Our aim was to evaluate the effects of medroxyprogesterone acetate (MPA) and the influence of menstrual cycle on the expression of TGFbeta1 and TGFbeta3 in human endometrium in vivo. In a double-blind, placebo-controlled trial, 46 healthy women with regular menstrual cycles received either MPA (10 mg/day) or placebo during 10 days. Endometrial and blood samples were collected 8-12 hours after the last MPA or placebo administration. Patients were classified into three groups according to biopsy dating and treatment: proliferative [tissue]/placebo, secretory [tissue]/placebo and secretory [tissue]/MPA. The immunohistochemical distribution of TGFbeta1 and TGFbeta1 mRNA was similar in all groups. Immunoreactive TGFbeta3 was present in the epithelium in 9.1% of proliferative samples, in 41.2% of secretory/placebo samples and in 87.5% of secretory/MPA samples (p=0.001). In the stroma, the frequency of TGFbeta3 staining was markedly increased after treatment with MPA (62.5%) compared to placebo (proliferative: 9.1%; secretory: 5.9%; p=0.005). The levels of TGFbeta3 mRNA increased during the secretory phase and were higher in the MPA-treated group, being directly correlated with morphological endometrial differentiation. It is concluded that MPA administration to healthy women increased TGFbeta3 but did not change TGFbeta1 gene and protein expression in the endometrium. This finding suggests that TGFbeta3 may be a local factor mediating progesterone- and progestogen-induced endometrial differentiation.

Adult↗
PubMed1992

No inhibitory effects of gestrinone and medroxyprogesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins.

The in vivo effects of gestrinone (R2323) and medroxyprogesterone acetate (MPA) on the estrogen production by rat ovaries were investigated. Hypophysectomized immature female rats treated with 2.5 or 5 IU of pregnant mare serum gonadotropin (PMS) were daily given vehicle only, gestrinone (0.5 mg/kg body weight) or MPA (10 mg/kg body weight), and the activities of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17, 20-lyase, 17 beta-hydroxysteroid dehydrogenase and aromatase in ovaries of these rats were measured. Gestrinone suppressed the 3 beta-hydroxysteroid dehydrogenase activity and increased activities of 17 alpha-hydroxylase, 17, 20-lyase and aromatase in ovaries stimulated by 5 IU of PMS, while MPA suppressed activities of 17 alpha-hydroxylase and aromatase in these ovaries. On the other hand, the aromatase activity in ovaries stimulated by 2.5 IU of PMS was suppressed by gestrinone and increased by MPA, and neither gestrinone nor MPA affected the production of aromatizable androgens from progesterone by these ovaries. Thus, gestrinone and MPA administrated in vivo showed divergent influences on steroidogenic enzyme activities in ovaries, but they did not affect the serum concentration of estradiol-17 beta. The present results suggest that neither gestrinone nor MPA reduced estrogen production by the rat ovary under the gonadotropin stimulation although they influenced some process of its steroidogenesis.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Improved continuation rate of depot-medroxyprogesterone acetate in adolescent mothers.

Poor compliance and high discontinuation rates of Depot-Medroxyprogesterone Acetate (DMPA) and other contraceptive methods are major factors in the continuing problem of adolescent pregnancy. In this study we attempted to determine if providing comprehensive health care for teen mothers and their babies would improve continuation rates of DMPA. Patients who started DMPA between 1/1/96 and 1/1/99 were included. Teen mothers and their babies received all their health care in this clinic, supported by State funding. Key elements regarding DMPA in this clinic were continuity of care, phone and mail reminders of appointments, free DMPA for patients without insurance, counseling at each visit and available evening clinic. In the study period a total of 299 (age 13-22 years) patients were started on DMPA. Fifty-one percent were white, 47% black and 2% others. Sixty-three percent were single, 20% married, 3% cohabitating and 14% undetermined (missing data). Seventy-eight percent had one baby and 22% more than one. A total of 189 patients (63.2%) continued to be compliant after one year of use and 101 patients (33.8% of total) continued beyond the second year. The most common side effect reported was bleeding or spotting (32%), However only seven patients (2.3%) discontinued use because of it. It is concluded that continuity of care (same staff and providers on each visit), regular counseling, flexible hours (evening appointments), financial ease (free DMPA and no visit charge for those without insurance), combined Teen-Tot health visits and regular reminders of appointments may help improve compliance and continuation rates in teen mothers leading to better success in preventing repeat teen pregnancy.

Adolescent↗
PubMed1998

Effect of medroxyprogesterone acetate on sex hormone-binding globulin mRNA expression in the human endometrial cancer cell line Ishikawa.

To understand the rationale of high-dose medroxyprogesterone acetate (MPA) in the treatment of well-differentiated uterine endometrial cancers, the effect of MPA on intracellular sex hormone-binding globulin (SHBG) mRNA expression in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by competitive reverse transcription-polymerase chain reaction-Southern blot analysis. Estradiol-17beta (E2, 10(-8) mol/l) did not alter SHBG mRNA expression, but the addition of 10(-10) mol/l MPA increased it, while a high concentration of MPA (10(-6) to 10(-5) mol/l) with or without E2 suppressed it. Furthermore. a high dose (10(-6) mol/l) of chlormadinone acetate or danazol with or without E2 significantly suppressed its expression, while MPA was the most effective among the hormones tested. The effect of MPA and the other steroid hormone analogs on SHBG expression was not mediated via the progesterone receptor. These findings suggest that intracellular SHBG suppression might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and may be involved as one of the mechanisms of the antitumoral effects of high-dose MPA on the development and growth of some well-differentiated endometrial cancer cells.

Antineoplastic Agents, Hormonal↗
PubMed1980

Advanced implantation in mink (Mustela vison) treated with medroxyprogesterone acetate during early embryonic diapause.

Adult and pubertal female mink mated on 4 March were administered 2.5 mg medroxyprogesterone acetate (MPA) or control vehicle on 9-11 March. Pregnancies were shorter (P less than 0.01) in adult (60 +/- 2 days) than in pubertal (72 +/- 0.7 days) control animals. Treatment with MPA reduced (P less than 0.01) the length of pregnancy in both adult (51 +/- 1 days) and pubertal (60 +/- 2 days) mink but did not significantly affect serum progesterone levels on 3-4 April. Observations at laparotomy during April confirmed the effects of age and treatment on the time of implantation and suggested that implantation sites become grossly visible 28 days before parturition. It is concluded that administration of a progestagen during early embryonic diapause can advance the time of implantation in mink.

Animals↗
PubMed2000

Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats.

Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0. 25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro.

Age Factors↗
PubMed2006

[Weight variation in users of the levonorgestrel-releasing intrauterine system, of the copper IUD and of medroxyprogesterone acetate in Brazil].

BACKGROUND: Assess weight variations in Brazilian users of the 20 microg/day levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) for comparison with a cohort of users of the TCu 380A intrauterine device (IUD) and a cohort of users of the injectable contraceptive, depot-medroxyprogesterone acetate (DMPA) over a period of five years. METHODS: A total of 163 users of the LNG-IUS, who had the device inserted in 1998, were admitted to the study. At the time of enrollment, each woman was matched by weight (+/- 1 kg) and age (+/- 1 year) to a woman using a TCu 380A IUD and to another woman using DMPA. All women were followed up for a period of five years. Each year weight was measured and the body mass index (BMI, kg/m2) was calculated. RESULTS: Age of the LNG-IUS users was 27.0 +/- 6.7 years (mean +/- SD), while age of the copper IUD users was 28.0 +/- 6.6 years and that of DMPA users was 26.9 +/- 6.5 years. Weight recorded at the onset of the study was 62.9 +/- 0.8 kg, 62.8 +/- 0.8 kg, and 62.5 +/- 0.9 kg (Mean +/- SD) for users of the LNG-IUS, the copper IUD, and DMPA, respectively. The BMI of women was initially 25.0 (+/- 0.3), 26.4 (+/- 0.3), and 25.5 (+/- 0.4), (Mean +/- SD), for users of the LNG-IUS, copper IUD, and DMPA, respectively. Weight increases of 3.1 kg, 4.9 kg and 8.2 kg were observed at the end of the fifth year among users of the LNG-IUS, copper IUD, and DMPA, respectively (p = 0.009). Increase of the BMI was also observed among all groups (final BMI was 26.3 +/- 0.7, 28.5 +/- 0.8 and 28.7 +/- 1.3 for users of the LNG-IUS, copper IUD and DMPA, respectively). Multivariate analysis showed that there was a significant association between weight increase and length of use of the contraceptive method and of the DMPA. CONCLUSION: The use of a LNG-IUS during five years caused no significant weight increase and the difference in weight was of the same magnitude as that of copper IUD users.

Adult↗