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PubMed2003

Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate: two-year substudy results.

OBJECTIVE: To determine the endometrial safety of 2 years of treatment with lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA). DESIGN: Randomized, double-blind, placebo-controlled, multicenter metabolic and osteoporosis substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study. SETTING: Nineteen study centers across the United States. PATIENT(S): Healthy, postmenopausal women (n = 822) with an intact uterus were recruited. INTERVENTION(S): Patients received CEE 0.625, CEE 0.625/MPA 2.5, CEE 0.45, CEE 0.45/MPA 2.5, CEE 0.45/MPA 1.5, CEE 0.3, CEE 0.3/MPA 1.5 (all doses mg/day), or placebo for 2 years. Endometrial biopsies were evaluated at baseline and years 0.5, 1, 1.5, and 2 using a centralized protocol. MAIN OUTCOME MEASURE(S): Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed estrogen (E). RESULT(S): No cases of endometrial hyperplasia were seen in the four CEE/MPA groups. For the CEE-alone groups, a dose-related increase in incidence rates from 3.17% (CEE 0.3 mg) to 27.27% (CEE 0.625 mg) was seen at 2 years. The number of cases increased from year 1 to year 2. For the CEE-alone groups, the incidence rates and types of hyperplasia diagnosed varied among the pathologists. CONCLUSION(S): Two years of treatment with lower doses of CEE/MPA provided endometrial protection comparable to that seen with commonly prescribed doses. These regimens should be considered for postmenopausal women who are candidates for hormone therapy.

Adult↗
PubMed2003

Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: a prospective, randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism. DESIGN: Prospective, randomized, double-blind, placebo-controlled, crossover trial. SETTING: Clinical research center, university hospital. PATIENT(S): Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy. INTERVENTION(S): Collection of serum and urine samples and measurement of bone density. Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks. RESULT(S): In both protocol A and B, LH and E(2) levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). CONCLUSION (S): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.

Adult↗
PubMed1975

Incidence of pregnancy, changes in menstrual pattern, and recovery of endometrial function after discontinuation of medroxyprogesterone acetate therapy.

The incidence of pregnancy, recovery of endometrial function, and changes in menstrual pattern were studied in 62 women who had received two or more intramuscular injections (150 mg) of medroxyprogesterone acetate (Depo-Provera) every three months and oral diethylstilbestrol (1 mg) daily for seven days every month. Immediately after discontinuing this therapy, 71% of the patients had regular menstrual cycles, 10% had irregular cycles, and 19% had amenorrhea. All the patients had regular cycles by the end of one year except one women who was probably menopausal. The average time required to conceive after stopping therapy was 9.3 months, range, 3 to 21 months). Conception was definitely delayed as shown by endometrial biopsies and the incidence of pregnancy. Within six months, 25% of the patients conceived and within one year, 69% conceived. By two years, four had not conceived. The percentage of pregnancies seemed to decrease with increased patient age.

Adolescent↗
PubMed1976

Plasma sex steroid and gonadotropin levels in control and silastic vaginal medroxyprogesterone acetate-impregnated ring cycles.

The concentrations of sex steroid hormones in plasma were determined daily in 14 young adult women, during both a control cycle and a treatment cycle. During the latter a Silastic ring into which 100 or 200 mg of medroxyprogesterone acetate (Provera) had been incorporated was worn intravaginally. During the treatment cycles, plasma levels of estradiol, progesterone, and 17-hydroxyprogesterone remained within the range observed during the early follicular phase. Testosterone and androstenedione levels did not show any cyclic variation during the treatment cycle; however, the mean levels were decreased by about 25% compared with the over-all plasma levels of the control cycle, whereas dehydroepiandrosterone levels were decreased by about 15%. It is concluded that these Provera-containing Silastic intravaginal rings inhibit ovulation and decrease androgen secretion by the ovaries significantly.

Adult↗
PubMed1977

Short-term effects of norethisterone oenanthate and medroxyprogesterone acetate on glucose, insulin, growth hormone, and lipids.

The effects on carbohydrate and lipid metabolism in 24 healthy female subjects of the long-acting steroid contraceptives norethisterone oenanthate (200 mg) (11 subjects) and depo-medroxyprogesterone acetate (150 mg) (13 subjects) were studied. The subjects were between the ages of 18 and 25 years, with a history of normal menstrual periods. Pretreatment levels of plasma cholesterol, plasma triglycerides, phospholipids, blood glucose, insulin, and growth hormone were compared with those obtained 3 weeks and 12 weeks after the initial injections. There were no statistically significant differences from the pretreatment levels in any of the values obtained at 3 weeks and 12 weeks in either group.

Adolescent↗
PubMed1977

Medroxyprogesterone acetate for the evaluation of hypertestosteronism in hirsute women.

Twenty-three women with moderately elevated plasma testosterone levels (77 to 240 ng/dl) received 10 mg of medroxyprogesterone acetate (MPA) orally, three times daily, for 3 months or more. The testosterone levels were reduced to normal (less than 70 ng/dl) in 21 patients, suppressed partially in 1 patient, and unchanged in 1 patient. The removal of an ovarian teratoma normalized the testosterone level in the patient whose levels had failed to suppress with MPA. On therapy, the mean plasma testosterone concentration decreased 60%, apparent free testosterone decreased 31%, and dihydrotesterone decreased 34% (P less than 0.001, P = 0.05, and P = 0.01, respectively). A small decrease in the testosterone-binding capacity did not reach statistical significance. Experience with this simple trial suggests that extensive diagnostic testing may not be required in women with hirsutism and moderately elevated testosterone levels.

Adolescent↗
PubMed1995

Sustained benefits of leuprolide acetate with or without subsequent medroxyprogesterone acetate in the nonsurgical management of leiomyomata uteri.

OBJECTIVE: To determine the effectiveness of leuprolide acetate (LA) followed by medroxyprogesterone acetate (MPA) in the treatment of abnormal uterine bleeding attributed to leiomyomata uteri. DESIGN: Randomized, double-blinded, controlled clinical trial. SETTING: Human volunteers in an academic research environment. PATIENTS: Premenopausal women with abnormal uterine bleeding attributed to leiomyomata uteri. INTERVENTIONS: Subjects received 6 months of LA after which they were randomized to receive MPA or placebo. MAIN OUTCOME MEASURES: Control of bleeding as assessed by menstrual calendar and self-report; hematologic parameters (hemoglobin and ferritin); uterine size by ultrasonography. RESULTS: More than three quarters of subjects became amenorrheic on LA. The proportion of subjects with improvement in the bleeding abnormality after therapy was not different in the group receiving MPA compared with placebo; however, women who received MPA were less likely to be anemic after therapy than women receiving placebo. Among the women assigned to placebo, 55% experienced an improvement in bleeding compared with pre-GnRH agonist therapy that persisted after discontinuation of LA. There was a high dropout rate (51%), largely associated with failure of the regimens to control bleeding symptoms. CONCLUSIONS: Approximately one half of women with abnormal bleeding attributed to leiomyomata uteri have sustained symptomatic improvement after 6 months of therapy with LA even when only placebo therapy is given, although MPA decreases the incidence of anemia. Leuprolide acetate with or without subsequent progestin may be useful as a component of nonsurgical management of these tumors, with monitoring of hematologic status. The interpretability of these data is limited by the high rate of therapy discontinuation in women with abnormal bleeding of the severity studied here.

Adult↗
PubMed1996

Medroxyprogesterone acetate supplementation diminishes the hypoestrogenic side effects of gonadotropin-releasing hormone agonist without changing its efficacy in endometriosis.

OBJECTIVE: To examine the effects of concomitant use of goserelin and medroxyprogesterone acetate (MPA) in the treatment of endometriosis. DESIGN: Thirty-eight women with laparoscopically confirmed endometriosis were treated with once-a-month s.c. injections of goserelin acetate 3.6 mg (Zoladex depot; Zeneca Pharmaceutics, Cheshire, United Kingdom) randomly combined with either MPA (100 mg daily; n = 19) or a placebo (one tablet daily; n = 19) in a double-blind trial. Symptoms and side effects were monitored for a treatment period of 6 months and a follow-up period of 6 months. Blood and urine samples were collected for the assessment of endocrine and biochemical parameters. A second-look laparoscopy was performed 6 months after the treatment in 29 women. RESULTS: The extent of endometriosis was diminished similarly in both treatment groups, as were pelvic symptoms. Fewer women in the MPA group had hot flushes and sweating at 3 and 6 months of treatment. Sex hormone-binding globulin decreased in the MPA group but not in the placebo group. Consequently, the E2 index (E2/SHBG X 100), reflecting the free fraction of E2, fell more in the placebo group than it did in the MPA group. The increased urinary excretion of calcium observed during placebo treatment was prevented by MPA. CONCLUSION: High-dose MPA combined with a GnRH agonist (GnRH-A) diminished some antiestrogenic effects of the agonist. A reduction in hypoestrogenic side effects and a possible bone-sparing effect can be regarded as beneficial, especially as the good effect of the GnRH-a on endometriotic implants and pelvic symptoms prevailed.

Adult↗
PubMed1996

Use of medroxyprogesterone acetate in the prevention of postoperative adhesions.

OBJECTIVES: To evaluate the efficacy of a commonly used progestogen, medroxyprogesterone acetate (MPA), in the prevention of postoperative adhesion formation. DESIGN: A double-blind, controlled study evaluated the efficacy of MPA to reduce postoperative adhesion formation and compared it with other adjuvants and controls in a rat model. SETTING: Animal Care Facility of an academic research setting. SUBJECTS: Seventy-five Sprague-Dawley female rats randomly divided into five groups. INTERVENTIONS: Three weeks before surgery, the animals from each group were administered an IM injection of one of the following regimens: [1] 15 mg MPA; [2] both 15 mg MPA and 0.75 mg leuprolide acetate (LA); [3] 0.75 LA; or [4] and [5] comparable volumes of sterile saline. A standardized surgical trauma was inflicted in all animals. Before abdominal closure, 2 mL of Ringer's Lactate was instilled in the abdominal cavity of all groups except group 5 (controls). Three weeks after surgery, the rats were killed and the adhesions were scored on a scale of 0 to 3 according to their size, thickness, and vascularity. MAIN OUTCOME MEASURE: Postoperative adhesions. RESULTS: The preoperative administration of MPA resulted in the least number and the least severe adhesions. The combination of LA and MPA did not reduce postoperative adhesion formation. Both Ringer's Lactate and LA reduced postoperative adhesions but not to the same extent as MPA. CONCLUSION: The preoperative administration of MPA in our laboratory animal model results in the most significant reduction of postoperative adhesion formation. This action of MPA may be mediated by the induction of both a progestational and a hypoestrogenemic milieu. However, the ultimate role of MPA in a clinical situation requires further investigation.

Abdomen↗
PubMed2001

Oral 17beta-estradiol and medroxyprogesterone acetate therapy in postmenopausal women increases HDL particle size.

Menopause is accompanied by changes in lipoprotein particles that include an increase in density of low density lipoproteins (LDL) and high density lipoproteins (HDL) particles. The effect of 3 months of oral hormone replacement therapy (HRT) on lipoprotein particle size in postmenopausal women who were randomized to (1) estrogen replacement therapy (ERT) alone (either 17beta-estradiol (1 mg) or conjugated equine estrogens (CEE) (0.625 mg); (2) combination therapy (17beta-estradiol plus medroxyprogesterone acetate (MPA) or CEE plus MPA); and (3) placebo were examined. Lipoprotein subclass concentrations and particle size were quantified by nuclear magnetic resonance spectroscopy (NMR). Combination HRT resulted in significant (P=0.002) increases in HDL particle size as compared with those on placebo formulations or ERT alone. Women assigned to combined HRT had lower concentrations of smaller HDL particles after 3 months (P=0.005) and higher concentrations of larger HDL particles (P=0.02), whereas women assigned to ERT or placebo experienced non-significant changes. In summary, combined HRT increases HDL particle size by altering concentrations of the smallest and largest HDL subspecies.

Administration, Oral↗
PubMed1989

Use of liquid chromatography in the synthesis of isoluminol-labeled medroxyprogesterone acetate and zeranol.

A high-performance liquid chromatographic (HPLC) method for monitoring the syntheses of two isoluminol-labelled drugs, medroxyprogesterone acetate (MPA) and zeranol, has been developed. MPA and the ketone derivative of zeranol, zearalanone, were conjugated to N-(4-aminobutyl)-N-ethylisoluminol through the carboxymethyloxime derivative of the drug by using the N-succinimide ester as an intermediary. Reaction mixtures were sampled periodically and chromatographed directly by HPLC on a silica gel column, by using isocratic elution with mixtures of hexane-ethanol-acetic acid in several different proportions. The degree of reaction completion was determined by comparison of the peak area of the initial reactant to that present at sampling time. MPA oxime production was found to be complete after 15 min; 97.0% of the oxime was converted to succinimide ester in 24 h; 99.0% of the available ester reacted within 2.5 h to form the final labelled product. Zearalanone oxime production was found to be complete after 2 h; 93.3% of the oxime was converted to the activated ester within 24 h; 89.6% of available ester had reacted in 30 min to form the final labelled product. The chromatography can be performed in real time, permitting modification in the conditions of the reaction while in progress.

Chemical Phenomena↗
PubMed1996

A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives.

OBJECTIVE: To examine bone density among adolescents receiving different forms of hormonal contraception along with that of control subjects. METHODS: Baseline and 1-year measures of lumbar vertebral bone density were obtained in girls receiving depot medroxyprogesterone acetate (Depo-Provera) (n = 15), levonorgestrel (Norplant) (n = 7), or oral contraceptives (n = 9) and in girls receiving no hormonal treatment (n = 17). In a subsample of Depo-Provera users (n = 8), Norplant users (n = 3), and control subjects (n = 4), bone density measurements were repeated after 2 years. Bone density was measured by dual-energy x-ray absorptiometry. RESULTS: Body mass indexes, level of pubertal development, substance use, and reproductive histories were not significantly different among the groups. More black girls were represented in the initial Depo-Provera group (p < 0.02), girls in the Norplant group exercised more hours per week (p < 0.02), and control subjects were older (p < 0.01) than those in the other groups. These variables did not significantly affect bone density results. After 1 year, bone density decreased 1.5% in Depo-Provera users, compared with increases of 2.5% in Norplant users, 1.5% in oral contraceptive users, and 2.9% control subjects (p < 0.02). After 2 years, bone density increased a total of 9.3% in Norplant users and 9.5% in control subjects but decreased a total of 3.1% in Depo-Provera users (p < 0.0001). CONCLUSION: These data suggest that Depo-Provera may, at least temporarily, suppress the expected skeletal bone mineralization in adolescents, whereas Norplant and oral contraceptives are associated with the expected increase in bone density in this population.

Adolescent↗
PubMed2003

Effects of tibolone and conjugated equine estrogens with or without medroxyprogesterone acetate on body composition and fasting carbohydrate measures in surgically postmenopausal monkeys.

The effects of tibolone on body weight, body composition, and fasting carbohydrate measures in surgically postmenopausal cynomolgus monkeys were compared to those of conjugated equine estrogens (CEE) with and without medroxyprogesterone acetate (MPA). Monkeys were fed a moderately atherogenic diet with either no hormones (control n = 29), CEE (0.042 mg/kg, n = 27), CEE + MPA (0.167 mg/kg, n = 29), low-dose tibolone (LoTib, 0.05 mg/kg, n = 30), or high-dose tibolone (HiTib, 0.20 mg/kg, n = 31) daily for 2 years. Body weight (BW) was measured throughout the study, and dual-energy x-ray absorptiometry (DEXA) scans of the abdominal region (lumbar vertebrae 1 through 5) were performed at the end of the trial to assess abdominal body composition. Fasting carbohydrate measures (glucose, insulin, C-peptide, and fructosamine) were determined at baseline and after 2 years of treatment. Compared to controls, BW significantly increased and abdominal soft tissue mass was greater (analysis of variance [ANOVA], P <.001, P = 0.003, respectively) in all but the CEE-treated group (P =.78, P =.94, respectively). HiTib-treated monkeys had greater abdominal lean mass compared to controls (P =.008), while there was no significant treatment effect on abdominal fat mass (analysis of covariance [ANCOVA], P =.29). Fasting insulin concentrations and fasting insulin/glucose ratios were greater in CEE + MPA- (P =.002, P =.03, respectively) and HiTib-treated monkeys (P =.03, P =.02, respectively) compared to controls. There was a strong trend for a treatment effect on fasting blood glucose concentration (ANCOVA, P =.06) with CEE + MPA-treated animals having the greatest values, despite no difference in fructosamine concentration (ANCOVA, P =.57). Using these fasting measures, the homeostasis model assessment (HOMA-IR) revealed significant insulin resistance with CEE + MPA treatment compared to controls (P =.008), while the quantitative insulin sensitivity check index (QUICKI) showed significantly impaired insulin sensitivity in all hormone replacement therapy (HRT) groups (all P values <.03), except CEE (P =.12). In conclusion, HRT with CEE + MPA or tibolone results in greater BW, abdominal soft tissue, and insulin resistance (CEE + MPA and HiTib) compared to control-treated monkeys.

Animals↗
PubMed2003

Effects of estrogen and medroxyprogesterone acetate on subpopulations of triglyceride-rich lipoproteins and high-density lipoproteins.

Hormonal replacement therapy (HRT) in postmenopausal women has been shown to increase both triglyceride (TG) and high-density lipoprotein (HDL) cholesterol levels. To better understand the effects of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), the 2 most commonly prescribed hormones in HRT, on the different subpopulations of TG-rich and HDL lipoproteins, we conducted a placebo-controlled, double-blind, randomized, crossover study consisting of 3 different phases in 14 postmenopausal women. The 3 phases, each 8-week long, included: (1) placebo, (2) CEE 0.625 mg/d, and (3) CEE 0.625 mg/d and MPA 2.5 mg/d. Slight and statistically nonsignificant elevations in TG levels were observed during the CEE treatment. While very-low-density lipoprotein (VLDL) cholesterol levels were not significantly affected by CEE and CEE + MPA, both HRT treatments lowered remnant lipoprotein (RLP) cholesterol (-14% and -37%, respectively). Compared with placebo, CEE caused a significant increase in HDL, HDL(2), apolipoprotein (apo) A-I, LpAI, alpha1, and prealpha1 levels (12%, 27%, 17%, 26%, 60%, and 102%, respectively). The combination therapy blunted the CEE effect on all HDL parameters, resulting in HDL, HDL(2), and LpAI levels being no longer significantly different from placebo. Apo A-I levels and alpha1, and prealpha1 levels were still significantly higher than placebo (+11%, +50%, and +112%, respectively). These results indicate that HRT has beneficial effects on RLP levels and that, while the estrogen component of HRT has a beneficial effect on the HDL subpopulations mostly associated with coronary heart disease (CHD) protection, MPA partially inhibits this effect.

Aged↗
PubMed1999

Effect of short-term medroxyprogesterone acetate on left ventricular mass: role of insulin-like growth factor-1.

Previous studies using 17beta-estradiol and medroxyprogesterone acetate (MPA) have shown that hormone replacement therapy (HRT) increases left ventricular mass (LVM). To determine if insulin-like growth factor-1 (IGF-1) is associated with the increase in LVM, we measured IGF-1 and IGF-binding protein-3 (IGFBP-3) levels in 19 postmenopausal women before and after 8 weeks of oral treatment with MPA 5 mg/d. LVM was measured by two-dimensional echocardiography. Changes in IGF-1, IGFBP-3, and LVM from baseline were analyzed by paired ttest. Regression analysis was used to determine if changes in the IGF-1 axis with MPA treatment affect the increase in LVM. LVM increased 4.4% during the study (P = .006 vbaseline). IGF-1 increased 17% with MPA (P = .008), whereas IGFBP-3 did not change. The IGF-1/IGFBP-3 ratio increased 16.8% (P = .0003). Regression analysis of LVM with IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio suggested that IGF-1 during MPA therapy explains 2.4% and the IGF-1/IGFBP-3 ratio explains 3.2% of the variation in LVM. There was no effect of IGFBP-3 on LVM. Most of the variation in LVM with MPA (90.5%) was explained by baseline LVM. The IGF-1/IGFBP-3 ratio on MPA treatment was inversely related to the change in LVM: women with a lower LVM at baseline had the greatest increase in LVM with MPA. These findings suggest that MPA increases IGF-1 and LVM. Because the increase in IGF-1 with MPA treatment explains a fraction of the increase in LVM, other mechanisms must also be operative.

Echocardiography↗
PubMed1988

Effects of medroxyprogesterone acetate on serum prolactin levels and liver prolactin binding capacity in the rat.

Modifications in liver prolactin (PRL) receptor levels and serum PRL concentration induced by administration of medroxyprogesterone acetate (MPA) were investigated in rats of both sexes. MPA induced a reduction both of the levels of PRL in the serum and of liver PRL receptors in the female rat. The reduction of the number of PRL receptors caused by MPA was rapid and almost complete after 10 days of treatment and appeared earlier than that of serum PRL levels. Furthermore the MPA-induced decrease in PRL receptors was specific, since insulin binding to the same liver membranes was not affected. MPA given simultaneously with oestradiol (which increases both the number of liver PRL receptors and the serum PRL levels in the male rats) was able to counteract the increase in PRL binding induced by oestradiol. On the contrary, the oestrogen-induced increase in serum PRL was not affected by MPA treatment. Similar results were obtained using tamoxifen, a well known antioestrogenic drug. In conclusion, our results show that the reduction of PRL receptor levels induced by MPA in rat liver is specific, not correlated to serum PRL concentration, and seems to depend on the antioestrogenic activity of the drug.

Animals↗
PubMed2000

Medroxyprogesterone acetate with acetazolamide stimulates breathing in cats.

Both medroxyprogesterone acetate (MPA) and acetazolamide (ACET) increase ventilation. Combined administration of these agents could result in an additional improvement of blood gases, for example in patients with chronic obstructive pulmonary diseases. The aim of this study in anaesthetized female (ovariohysterectomized, pre-treated with 17-beta-estradiol) cats was to compare the effects on the CO2 response curve of MPA alone (4 microg kg(-1), i.v.) with those after MPA followed by ACET (4 mg kg(-1) i.v.). We performed dynamic end-tidal CO2 forcing and analysed the data with a two-compartment model comprising a fast peripheral and slow central compartment, characterized by CO2 sensitivities (Sp and Sc, respectively) and a single offset (the apnoeic threshold B). MPA reduced Sp from 0.22 +/- 0.09 (mean +/- S.D.) to 0.13 +/- 0.06 L min(-1) kPa(-1) (P < 0.01) and Sc from 1.01 +/- 0.38 to 0.88 +/- 0.32 L min(-1) kPa(-1) (P < 0.01). B decreased from 4.02 +/- 0.27 to 3.64 +/- 0.42 kPa (P < 0.01). Subsequent administration of ACET reduced Sp and Sc further to 0.09 +/- 0.06 and to 0.70 +/- 0.49 L min(-1) kPa(-1) (P < 0.01), respectively. The apnoeic threshold decreased further to 2.46 +/- 1.50 kPa (P < 0.01). Because both treatments reduced ventilatory CO2 sensitivity, we conclude that a simulating effect on ventilation is due to a decrease in the apnoeic threshold. Combined administration of MPA and ACET may lead to larger increases in ventilation than treatment with either drugs alone.

Acetazolamide↗
PubMed2003

Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate.

Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive with worldwide availability. However, it is associated with a high incidence of breakthrough bleeding (BTB) during the first 6 months of use which often leads to discontinuation. Mifepristone is a progesterone receptor antagonist that has been demonstrated to decrease BTB caused by the levonorgestrel subdermal implant (Norplant). The purpose of this study was to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with bleeding intervals > or =8 and > or =14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors.

Adult↗