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Depot medroxyprogesterone versus norethisterone oenanthate for long-acting progestogenic contraception.

BACKGROUND: There are two injectable progestogen-only contraceptives (IPCs) that have been available in many countries in the world since 1983. They are both still extensively used in many developing countries, forming a large proportion of the health system's expenditure on contraception. These are depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN). These are both highly effective contraceptives that receive wide acceptance amongst women in their fertile years. They differ in frequency of administration that has implications on patient uptake. They also differ in cost that may significantly affect budgeting in the health system. A systematic comparison will aid to ensure their rational use. OBJECTIVES: To determine if there are differences between depot medroxyprogesterone acetate given at a dose of 150 mg IM every 3 months and norethisterone oenanthate given at a dose of 200mg IM every 2 months, in terms of contraceptive effectiveness, reversibility and discontinuation patterns, minor effects and major effects. SEARCH STRATEGY: We searched the computerized databases MEDLINE using PubMed, Popline, Cochrane Controlled Trials Register, Biblioline, LILACS, EMBASE and PASCAL for randomised controlled trials of DMPA versus NET-EN for long-acting progestogenic contraception. Studies were included regardless of language, and all databases were reviewed from the time that injectable progestogens have been in use. SELECTION CRITERIA: All randomised controlled comparisons of DMPA acetate given at a dose of 150 mg IM every 3 months versus NET-EN given at a dose of 200mg IM every 2 months, used for contraception, were included. Trials had to report on contraceptive efficiency and return to fertility, discontinuation risks and reasons for discontinuation, and clinical effects, both menstrual and non-menstrual. DATA COLLECTION AND ANALYSIS: BD and CM evaluated the titles and abstracts obtained through applying the search strategy and applied the eligibility criteria. BD attempted to contact authors where clarification of the data was required, and contacted all main manufacturers of the contraceptives. After inclusion of the two studies, the data was abstracted and analysed with RevMan 4.2. MAIN RESULTS: Two trials were included in this review. There was no significant difference between the two treatment groups for the frequency of discontinuation for either contraceptive, although the women on NET-EN were 4% more likely to discontinue for personal reasons than those on DPMA. Discontinuation because of accidental pregnancy did not differ between the groups. Although the duration of bleeding and spotting events was the same in each group, women on DPMA were 21% more likely to develop amenorrhoea. Mean changes in body weight at 12 and 24 months, and in systolic and diastolic blood pressure at 12 months did not differ significantly between the studies. AUTHORS' CONCLUSIONS: While the choice between DPMA and NET-EN as injectable progestogen contraceptives may vary between both health providers and patients, data from randomized controlled trials indicate little difference between the effects of these methods, except that women on DMPA are more likely to develop amenorrhoea. There is inadequate data to detect differences in some non-menstrual major and minor clinical effects.

Contraception↗

The effect of medroxyprogesterone acetate on blood pressure.

Twenty-four women (21 normotensive and 3 hypertensive) aged 16-35 years received 150-mg injections of medroxyprogesterone acetate (MPA) for contraception. Their blood pressure (BP) was measured under basal conditions by the same nurse before treatment and at 1-, 2- and 3-month intervals. Their mean BP fell from 124.1/79.4 to 119.8/74.6 mm Hg at one month (p less than 0.05 for diastolic pressure) to 117.0/74.9 mm Hg at two months and to 115.6/73.2 mm Hg at three months. When the normotensive patients were analyzed separately, their BP fell, but not significantly. Only one patient had a rise of 20 mm Hg systolic, but she remained normotensive. We conclude that medroxyprogesterone acetate does not raise BP.

Adolescent↗

Oral medroxyprogesterone in the treatment of metastatic breast cancer.

In 47 postmenopausal women with evaluable breast cancer, oral medroxyprogesterone acetate (MPA) was given at a daily dose level of 400 mg. Patients with negative estrogen receptors, poor performance status, or nonresponse to previous endocrine therapy were excluded from this study. There were 25 (53%) responders to this agent. Periods of remission ranged from 5-26 months with a median of 10 and a mean of 12+ months. Higher rates of response were noted in women over 50 years of age, in patients with osseous metastasis, and in patients with a longer disease-free interval. Adverse effects included weight gain, Cushingoid appearance, skin rash, and vaginal discharge. In this selected group of patients, oral medroxyprogesterone at a dose level of 400 mg/day appeared to provide a significant frequency of tumor response.

Adult↗

The effect of tamoxifen and medroxyprogesterone on giant cell formation by monocytes from patients with breast cancer.

Incubation of peripheral blood monocytes from patients with breast cancer under agarose for 6 days at 37 degrees C in a 5% CO2 atmosphere resulted in giant cell formation. This phenomenon appeared to be mediated by retroviruses present in these cells. In this study giant cell formation was investigated in patients with primary stage I and II breast cancer before and 3 months after mastectomy with axillary lymph node clearance. Mastectomy had no significant inhibitory effect on giant cell formation. In vitro incubation of monocytes from patients with breast cancer in the presence of tamoxifen (Nolvadex) resulted in significant inhibition of giant cell formation (P less than 0.000003; paired Student's t-test). In vitro addition of medroxyprogesterone (Farlutal) to monocytes from patients with breast cancer also resulted in significant inhibition of giant cell formation (P less than 0.003: paired Student's t-test). Furthermore, incubation of monocytes from patients treated by mastectomy followed by 3 months treatment with adjuvant tamoxifen, resulted in a significant reduction (P less than 0.00007; paired Student's t-test) in the number of giant cells compared to the same samples tested before the commencement of the treatment. Giant cell formation may be used as a simple test to predicte the response of patients with breast cancer to either tamoxifen or medroxyprogesterone.

Adult↗

Medroxyprogesterone acetate, enoxaparin and pentoxyfylline cause alterations in lipid peroxidation, paraoxonase (PON1) activities and homocysteine levels in the acute oxidative stress in an experimental model of spinal cord injury.

BACKGROUND: Effects of medroxyprogesterone acetate, enoxaparin and pentoxyfylline on lipid peroxidation, antioxidant defence system, paraoxonase activities, and homocysteine levels in an experimental model of spinal cord injury were investigated. METHOD: Sixty-three male albino Wistar rats were anaesthetized by 400 mg/kg chloral hydrate and divided into 5 groups. G1 (n 7) = control group provided the baseline levels. G2-G5 underwent T3-6 total laminectomies and spinal cord injuries by clip compression at T4-5 levels. Medications were applied to G3-G5 right after the injury. Hence, G2 constituted laminectomy + injury (lam+I); G3 = lam + I + medroxyprogesterone acetate (MPA), G4 = lam + I + enoxaparin (E), and G5 = lam+I+pentoxyfylline (P) groups. Animals were decapitated either at the 1st or 4th hour after injury. Tissue and blood malonyldialdehyde (MDA) and plasma homocysteine and erythrocyte superoxide dismutase (SOD) levels, and erythrocyte glutathione peroxidase (GSH-Px) and plasma paraoxonase (PON1) activities were assayed. SPSS 9.0 program was used for statistical analysis and graphics. Intergroup comparisons were made by Bonferroni corrected Mann Whitney U test ( P<0.025), and intragroups comparisons by Wilcoxon Rank test ( P<0.03). FINDINGS: In intergroup comparison, G1-G2, G1-G3, G1-G5, G2-G3, G2-G4, and G4-5 groups differed from each other for all parameters ( P<0.025, MWU) except for G4-G5 4th hour MDA levels. G1-G4 was similar for all 1st hour parameters ( P>0.025, MWU), but different for 4th hour ( P<0.025, MWU) except for GSH-Px and SOD levels. For G2-G5, all parameters for 1st and 4th hour were similar except for 4th PON1, Hcy and SOD levels. For G3-G4, all 1st hour parameters were different from each other ( P<0.025, MWU); whereas all 4th hour parameters were similar except for SOD level. For G3-G5, all parameters at 1st and 4th hour were similar except for 4th hour GSH-Px, PON1, and Hcy. In intragroup comparison, all parameters differed from each other at all times (P<0.03, WRT) except for 1st hour G4 MDA, Hcy and SOD levels compared to basal levels. INTERPRETATION: In injury groups, plasma Hcy levels decreased and PON1 activities increased as erythrocyte SOD level and GSH-Px activities decreased in parallel to increases of tissue and blood MDA levels. These changes were relatively suppressed by MPA, enoxaparin and pentoxyfylline administrations at varying degrees. Enoxaparin was the most powerful agent, particularly at 1st hour. MPA was also effective, particularly at 4th hour. Pentoxyfylline despite having slight effect at 4th hour, was not effective according to both control and injury groups. Enoxaparin and MPA can be used in the treatment of spinal cord injuries. PON1 and Hcy are helpful in monitoring the antioxidant defence system as well as SOD and GSH-Px, both in injury and medically treated groups.

Animals↗

Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.

The addition of the synthetic progestin medroxyprogesterone acetate (MPA) to postmenopausal estrogen therapy significantly increases breast cancer risk. Whether this adverse effect is specific to MPA or characteristic of all progestogens is not known. The goal of this study was to compare the effects of oral estradiol (E2) given with either MPA or micronized progesterone (P4) on risk biomarkers for breast cancer in a postmenopausal primate model. For this randomized crossover trial, twenty-six ovariectomized adult female cynomolgus macaques were divided into social groups and rotated randomly through the following treatments (expressed as equivalent doses for women): (1) placebo; (2) E2 (1 mg/day); (3) E2 + P4 (200 mg/day); and (4) E2 + MPA (2.5 mg/day). Hormones were administered orally, and all animals were individually dosed. Treatments lasted two months and were separated by a one-month washout period. The main outcome measure was breast epithelial proliferation, as measured by Ki67 expression. Compared to placebo, E2 + MPA resulted in significantly greater breast proliferation in lobular (P < 0.01) and ductal (P < 0.01) epithelium, while E2 + P4 did not. Intramammary gene expression of the proliferation markers Ki67 and cyclin B1 was also higher after treatment with E2 + MPA (P < 0.01) but not E2 + P4. Both progestogens significantly attenuated E2 effects on body weight, endometrium, and the TFF1 marker of estrogen receptor activity in the breast. These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for postmenopausal breast cancer than medroxyprogesterone acetate.

Animals↗

Prevention of osteoporosis by medroxyprogesterone acetate in postmenopausal women.

The effect of medroxyprogesterone acetate 10 mg BID alone, conjugated estrogens alone or in a combination regimen for the prevention of osteoporosis was determined in 36 postmenopausal women using single photon densitometry. No significant differences in cortical or trabecular bone mass over time were detected in women between the three treatment groups, although a slight increase in bone mass was noted in women with the combined therapy. Medroxyprogesterone acetate appears efficacious in preventing postmenopausal osteoporosis, and may be especially useful in women with contraindications to estrogen replacement therapy.

Adult↗

Effect of continuous oestradiol-medroxyprogesterone administration on plasma lipids and lipoproteins.

Plasma lipids and lipoproteins were measured in 21 post-menopausal women after 4 and 8 months of continuous treatment with an orally administered combination of oestradiol and medroxyprogesterone acetate. The mean concentrations of cholesterol and low-density-lipoprotein (LDL) cholesterol were reduced by 12% (P less than 0.001) and 11% (P less than 0.01), respectively, after 4 months of treatment and by 9% (P less than 0.05) and 12% (P less than 0.05) after 8 months. The mean level of high-density-lipoprotein (HDL) cholesterol showed an initial fall of 5% (P less than 0.05) after 4 months and then increased by 13% (P less than 0.05) after 8 months of treatment. The plasma triglycerides level oscillated around the baseline value, but the changes were not statistically significant. Indexes such as the HDL-cholesterol/LDL-cholesterol and cholesterol/HDL-cholesterol ratios, which are considered to be good indicators of atherogenic risk, showed changes towards patterns considered to be beneficial. Although the clinical significance of these changes remains uncertain at present, it seems clear that an oestradiol and medroxyprogesterone combination administered continuously produces biochemical changes which are regarded as protective against cardiovascular disease. Additionally, the endometrial inertness attributed to the continuous oestrogen-progestogen therapy would warrant its use as a good alternative in post-menopausal replacement therapy.

Adult↗

Suppression of ovulation by a new subcutaneous depot medroxyprogesterone acetate (104 mg/0.65 mL) contraceptive formulation in Asian women.

BACKGROUND: A new progestin-only, nondaily depot medroxyprogesterone acetate (DMPA) SC injectable contraceptive suspension (104 mg/0.65 mL) has been developed. Clinical trials (including dose-ranging, pharmacokinetic/pharmacodynamic, and contraceptive efficacy studies) indicating the effectiveness of this new formulation were conducted primarily in white women. However, results of an early study by the World Health Organization suggested that in Thai women, medroxyprogesterone acetate (MPA) may be metabolized in <91 +/- 7 days (the range for effective suppression of ovulation established in clinical trials), resulting in a faster return to ovulation in this population. OBJECTIVES: This study was designed to determine the duration of ovulation suppression and investigate the pharmacokinetic profile of MPA after a single SC injection of DMPA 104 mg/0.65 mL in Asian women. It also assessed the effect of ethnicity and injection site on the duration of ovulation suppression. METHODS: : This was a single-center, single-dose, open-label outpatient trial conducted in Singapore in Asian women aged 18 to 40 years. After 1 control cycle, women with confirmed ovulation were randomized in a 1:1 ratio to receive an SC injection of DMPA 104 mg/0.65 mL in either the anterior thigh or the abdomen. Serum concentrations of MPA, progesterone, estradiol, luteinizing hormone, and follicle-stimulating hormone were measured during the 91-day dosing interval and for an additional 15 days thereafter. RESULTS: Twenty-four Asian women (mean [SD] age, 33.8 [43] years; range, 22.7-40.1 years; mean [SD] body mass index, 22.4 [3.0] kg/m(2)) belonging to 5 ethnic groups (Chinese, Filipino, Indian, Malaysian, and Thai) were included in the study Ovulation suppression was maintained throughout the 91-day dosing interval, regardless of ethnicity or injection site. Ovulation was suppressed for at least 112 days after injection in 23 (95.8%) women, as evidenced by maintenance of serum progesterone concentrations <4.7 ng/mL. The pharmacokinetic parameters for MPA in these Asian women were similar to those previously reported in white women. The most frequently reported adverse events were flulike symptoms and headache, all of mild to moderate intensity. No serious adverse events were reported. CONCLUSIONS: In this study, SC DMPA 104 mg/0.65 mL provided effective suppression of ovulation for at least 91 days in Asian women. Ethnicity and injection site had no effect on MPA profiles.

Adult↗

Bone mineral density and depot medroxyprogesterone acetate.

INTRODUCTION: Depot medroxyprogesterone acetate (DMPA) suppresses pituitary gonadotrophin output, thus, suppressing ovulation. Estrogen production from the ovary is also strongly inhibited, and the resulting estrogen deficiency has a detrimental impact on bone. Depot medroxyprogesterone acetate may be particularly detrimental in young women, as it may impede attainment of peak bone mass, and switching to a different contraceptive is recommended. However, the effect of sequential use of DMPA with other contraceptives in this age group has not been investigated. METHODS: This was a cross-sectional analysis of 218 DMPA users who were 20 years or older (mean, 31 years, +/-8.9 SD) at the time of bone mineral density (BMD) estimation. The majority of women had used one or more contraceptive beside DMPA. The most commonly used alternative contraceptive was the oral combined pill (OCP). It was used by 65% of women (n=143) and for an average duration of 6 years. A logistic regression model was used to estimate the association between potential risk factors and low bone mass. RESULTS: The prevalence of low bone mass at either hip or spine (T< or =1) was 41%. The prevalence of a T score below -2.5 was 5%, and 45% of women had already sustained one fracture. Younger age was associated with higher BMD [odds ratios (ORs), 0.054; 95% confidence interval (CI), 0.007-0.431]. However, this protective effect of age was lost once the interaction between the duration of both DMPA and OCP was introduced into the model (OR for low BMD, 1.42; 95% CI, 1.09-1.8). The use of DMPA first before ever use of OCP was particularly detrimental to BMD (OR, 3.94; 95% CI, 1.08-14.0). On the contrary, body mass index was positively associated with BMD (OR, 0.86; 95% CI, 0.8-0.9). No other demographic or anamnestic variables significantly predicted the presence of low BMD in this group of young women. This group of DMPA users appear to be at a very high risk of both low BMD and fractures, possibly independently of DMPA use. This needs to be considered when writing guidelines for risk assessment. CONCLUSION: The use of DMPA before achievement of peak bone mass may be particularly detrimental to bone, but switching DMPA with the OCP in these women does not seem to confer specific benefit in terms of bone density. This needs to be taken into consideration when a change in contraceptive is considered purely for the sake of bone protection.

Adult↗

Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain.

OBJECTIVE: To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA-SC 104) with that of leuprolide acetate in treatment of endometriosis. DESIGN: Phase 3, multicenter, randomized, evaluator-blinded, comparator-controlled trial. SETTING: Clinical trial sites in Canada and United States. PATIENT(S): Two hundred seventy-four women with surgically diagnosed endometriosis. INTERVENTION(S): Intramuscular injections of DMPA-SC (104 mg) or leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months of posttreatment follow-up. MAIN OUTCOME MEASURE(S): Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density (BMD), hypoestrogenic symptoms, bleeding, and weight. RESULT(S): The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (month 6) and in reducing all five symptoms after 12 months' follow-up (month 18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6, with scores returning to baseline at 12 months' follow-up. No statistically significant differences in median weight changes were observed between groups. Compared with leuprolide, DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding. CONCLUSION(S): Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding.

Adult↗

Decreased suppression of interleukin-6 after treatment with medroxyprogesterone acetate and danazol in endometrial stromal cells of women with adenomyosis.

OBJECTIVE: To examine changes in local cytokine production in the eutopic endometrium of adenomyosis after treatment with medroxyprogesterone acetate (MPA) and danazol. DESIGN: Prospective cohort study. SETTING: Tertiary university hospital. PATIENT(S): Twenty-four women with adenomyosis (study group) and 22 women without adenomyosis (control group). INTERVENTION(S): Eutopic endometrium was separated into single endometrial stromal cells (ESCs), and was cultured in vitro alone, with MPA (10(-7) M), or with danazol (10(-7) M) for 8 days. MAIN OUTCOME MEASURE(S): Messenger RNA expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha in ESCs, and their concentrations in the supernatants of ESCs. RESULT(S): A significant decrease of IL-6 concentration in the supernatant, measured by ELISA, was found with time of ESCs cultured with MPA and danazol in the control group, but not in adenomyosis. The IL-6 mRNA in ESCs determined by real-time quantitative polymerase chain, as well as its concentration in the supernatant, was much higher in adenomyosis than that in the control group after treatment with MPA and danazol for 8 days. CONCLUSION(S): Medroxyprogesterone acetate and danazol appeared to have a decreased effect on the suppression of IL-6 liberated by ESCs in adenomyosis. This aberrant secretion of IL-6 might play a role in the formation of ectopic endometrial implants in adenomyosis.

Cells, Cultured↗

The effects of 17 beta-oestradiol plus dydrogesterone compared with conjugated equine oestrogens plus medroxyprogesterone acetate on lipids, apolipoproteins and lipoprotein(a).

OBJECTIVE: To compare the effects of 17 beta-oestradiol plus dydrogesterone with conjugated equine oestrogens plus medroxyprogesterone acetate on serum lipids, apolipoproteins and lipoprotein(a) in postmenopausal women. METHODS: A multi-centre, prospective, randomised, double-blind, comparative one-year study in 362 healthy postmenopausal women aged 39-74 years with an intact uterus. Fasting blood samples were taken at baseline and after 28 and 52 weeks of treatment. Participants received daily oral treatment with continuous combined 1 mg micronised 17 beta-oestradiol/5 mg dydrogesterone (E/D: n=180) or 0.625 mg conjugated equine oestrogens/5 mg medroxyprogesterone acetate (CEE/MPA: n=182). RESULTS: Significant differences between the two groups after 52 weeks were observed for total cholesterol (E/D: -1.7%; CEE/MPA: -7.3%), LDL-cholesterol (E/D: -4.5%; CEE/MPA: -11.3%), HDL-cholesterol (E/D: +15.3%; CEE/MPA: +7.5%), triglycerides (E/D: +9.8%; CEE/MPA: +16.6%), VLDL-triglycerides (E/D: -3.3%; CEE/MPA: +10.0%), lipoprotein(a) (E/D: 0.0%; CEE/MPA: -25.2%) and for the ratio apolipoprotein B/LDL-cholesterol (E/D: +0.9%; CEE/MPA +5.9%). CONCLUSIONS: E/D and CEE/MPA differ in their anti-atherogenic effects on lipids and lipoproteins. This however can not easily be translated to differences in clinical cardiovascular outcomes.

Adult↗

Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: The objectives of this study were to estimate the clinical response rate and toxicity of daily tamoxifen combined with intermittent weekly medroxyprogesterone acetate (MPA). METHODS: This study reports the results of 61 patients with measurable advanced or recurrent endometrial carcinoma enrolled on this study to be treated with tamoxifen 40 mg p.o. daily plus alternating weekly cycles of MPA 200 mg p.o. daily. RESULTS: One patient was excluded and two patients did not receive study treatment. The percent of patients responding (6 complete and 13 partial) was 33% (95% confidence interval [CI]: 21-46%) among 58 eligible patients who received therapy. Median progression-free survival (PFS) was 3 months and median overall survival (OS) was 13 months. CONCLUSION: The combination of daily tamoxifen and intermittent weekly medroxyprogesterone acetate is an active treatment for advanced or recurrent endometrial carcinoma. Further investigation of this combination is appropriate.

Aged↗

Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone.

OBJECTIVES: The aim of the study was to investigate apoptosis as a growth regulatory mechanism of gestagen in endometrial precancers and to compare differences in the apoptotic cascade after high and low dose gestagen regimens. METHOD: Pre- and post-treatment paraffin-embedded endometrial hyperplasia specimens from women treated with levonorgestrel intrauterine device (n = 26) and women treated with 10 mg medroxyprogesterone for 10 days per cycle (n = 31) were examined for changes in the expression of Bcl-2 and BAX and the extent of apoptosis after 3 months of treatment. Immunohistochemical expression in tissue specimens for Bcl-2 and BAX was evaluated by H-score. Average number of apoptotic cells per hundred cells within ten different high power field (40 x) was evaluated for each section after in situ apoptosis detection (TUNEL method). A second group of patients with endometrial hyperplasia was examined after 1 week treatment with levonorgestrel IUD (n = 6) or medroxyprogesterone (n = 5) to determine early effects on expression of Bcl-2 and BAX and the extent of apoptosis. RESULTS: All the patients in the IUD group (n = 31) but only about half of the patients in per oral group (16 of 26) responded to treatment. The glandular reduction in Bcl-2 expression was markedly greater for the IUD patients than for the patients who received oral gestagen. The decrease in BAX expression after IUD treatment was less than the reduction of Bcl-2. Decrease in glandular Bcl-2 after 3 months of treatment was coincident with a significant increase in the measurable amount of apoptosis. In stromal cells, the increase in expression of Bcl-2 and BAX was found after gestagen treatment, the response being much more marked for the IUD group. The non- responders to per oral gestagen had no Bcl-2 expression in stroma after 3 months of therapy whereas an increase was observed for the responders. After 1 week, glandular Bcl-2 expression was significantly reduced after treatment in the IUD group. As for the rest, no changes were detected in either of the groups. CONCLUSION: Our results indicate that proteins in the apoptotic cascade are regulated by gestagen therapy in human endometrial precancers. Expression of these proteins is shown to be dependent on administration form and/or type of gestagen. Stromal Bcl-2 expression appears to be a potential biomarker which can separate responders of gestagen treatment from non-responders after oral administration.

Administration, Oral↗

Compliance with depot medroxyprogesterone acetate: a randomized, controlled trial of intensive reminders.

We enrolled women in a prospective, randomized study to determine whether an intensive reminder system would improve compliance in women receiving depot medroxyprogesterone injections. Women selecting this treatment were assigned to a group that received both mail and telephone reminders or to a second group that received only a scheduled appointment at the time of the previous injection. The rate of continuation and the rate of on-time injections did not differ between groups. Women who had prolonged bleeding were more likely to discontinue depot medroxyprogesterone injections.

Adult↗

Bone mineral density in adolescent and young Thai girls receiving oral contraceptives compared with depot medroxyprogesterone acetate: a cross-sectional study in young Thai women.

This cross-sectional study of bone mineral density in adolescent and young Thai girls receiving oral contraceptives compared with depot medroxyprogesterone acetate was performed to evaluate the differences among these groups. Thirty current OC users and 30 current depot medroxyprogesterone acetate (DMPA) users were included in the study. The mean duration of OC use was 28.8 +/- 3.4 months and of DMPA 24.6 +/- 3.3 months. Dual energy X-ray absorptiometry (DEXA) was used to measure bone mineral density (BMD) at distal and ultradistal forearm of the nondominant side. The BMD of ultradistal forearm of OC users and that of DMPA users were 0.423 +/- 0.048 and 0.403 +/- 0.039 g/cm(2) and at distal forearm of OC and DMPA users were 0.566 +/- 0.043 and 0.571 +/- 0.064 g/cm(2), respectively. However, there were no statistical differences in BMD in these two groups.

Absorptiometry, Photon↗

Medroxyprogesterone acetate does not antagonize estrogen-induced increases in endothelium-dependent vasodilation: potential clinical implications.

OBJECTIVE: Determine the effect of combined 17beta-estradiol benzoate (E2) and medroxyprogesterone acetate (MPA) administration on endothelium-dependent vasorelaxation to acetylcholine (ACh). DESIGN: Prospective, ex vivo study. SETTING: Academic research laboratory. ANIMAL(S): Mature female rats. INTERVENTION(S): Ovariectomized rats received one of the following interventions daily for 3 days: [1] corn oil via IM injection, [2] E2 (20 microg/kg IM), or [3] E2 (20 microg/kg IM) and MPA (10 mg/kg IM). MAIN OUTCOME MEASURE(S): Basal release of nitric oxide (NO) and endothelium-dependent and endothelium-independent vasodilation from thoracic aortas obtained from each group. RESULT(S): Estradiol treatment potentiated the endothelium-dependent relaxation to ACh when compared with the control group. Administration of MPA with E2 did not antagonize the beneficial effect of E2 on endothelium-dependent relaxation. Estradiol treatment alone or in combination with MPA did not affect endothelium-independent vasodilation as compared with the case of the control group. Administration of E2 resulted in increased basal NO release (assessed indirectly by measuring the constrictor response to N(G)-nitro-L-arginine [methyl ester (L-NAME)]) when compared with the case of the control group, and the addition of MPA to E2 did not alter the effect of E2 on basal NO release. CONCLUSION(S): Estradiol potentiates endothelium-dependent relaxant responses and increases basal endothelial NO release. Medroxyprogesterone acetate does not antagonize these effects of E2.

Acetylcholine↗