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PubMed1996

Management of abnormal uterine bleeding.

Patients treated for dysfunctional uterine bleeding are separated into two groups: those with acute bleeding episodes and those with chronic repetitive bleeding problems. An acute bleeding episode is best controlled with the use of high-dose estrogen. A curettage is indicated for patients with acute bleeding resulting in hypovolemia, and a curettage or hysteroscopically directed biopsies is indicated for women with risk factors for endometrial cancer who have persistent bleeding problems. The management of anovulatory dysfunctional uterine bleeding is determined by the needs of the patient. In the adolescent medroxyprogesterone acetate is administered orally once a day for 10 days each month for > or = 3 months, and the patient is monitored closely thereafter. Oral contraceptives are used for women of reproductive age with anovulatory bleeding episodes who also require contraception. Clomiphene citrate is used for women of reproductive age with anovulatory bleeding who want to conceive. Oral medroxyprogesterone acetate is administered 10 days each month for 6 months for the treatment of anovulatory dysfunctional uterine bleeding alone in this age group. For the perimenopausal patient dysfunctional uterine bleeding may be treated by the administration of cyclic progestin or cyclic conjugated equine estrogens for 25 days with the concomitant administration of medroxyprogesterone acetate for days 18 to 25. The perimenopausal patient with dysfunctional uterine bleeding who is a nonsmoker and does not have evidence of vascular disease may also be treated with low-dose combination oral contraceptives. The long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage. The long-term therapy is directed at the reduction in menstrual blood loss. For these patients prolonged progestin use, oral contraceptives, nonsteroidal antiinflammatory drugs, antifibrinolytic agents, danazol, and as a last resort gonadotropin-releasing hormone agonists are part of the therapeutic armamentarium. A combination of two or more of these agents is often required to successfully control the abnormal bleeding. For patients who no longer desire future fertility and have associated pelvic pathologic disorders or for those who fail all medical regimens, surgical therapy may be considered. Either hysterectomy or endometrial ablation has been used. Patients with von Willebrand's disease and excessive menstrual blood loss may be misdiagnosed as having dysfunctional uterine bleeding. van Willebrand's disease is the most common bleeding disorder and is present in approximately 1% of the population. It is much more common than previously recognized. There are improved diagnostic tests to identify this disorder and, most important, there is a high-concentration desmopressin acetate nasal spray available as treatment that does not involve the risk of transmission of hepatitis and human immunodeficiency virus.

Female↗
PubMed1997

Is bleeding a predictor of endometrial hyperplasia in postmenopausal women receiving hormone replacement therapy? Menopause Study Group (United States, Italy, Netherlands, Switzerland, Belgium, Germany, and Finland.

OBJECTIVE: We evaluated bleeding as a predictor of endometrial hyperplasia in postmenopausal women receiving conjugated estrogens (Premarin) alone or with medroxyprogesterone acetate. STUDY DESIGN: This study was a retrospective assessment of bleeding and endometrial histologic data gathered during the prospective Menopause Study Group trial. RESULTS: Approximately 20% of women (n = 57) who received unopposed conjugated estrogens for 1 year had endometrial hyperplasia. These women (n = 56) had more bleeding days than did women who did not have hyperplasia (p < 0.001). For users of unopposed conjugated estrogens, the predictive value of amenorrhea to indicate a nonhyperplasia diagnosis was 95%. Irregular bleeding did not appear to be indicative of hyperplasia when continuous or cyclic medroxyprogesterone acetate was added to conjugated estrogens. CONCLUSION: Unanticipated prolonged bleeding in postmenopausal women receiving unopposed estrogen is suggestive of endometrial hyperplasia. Some irregular bleeding is anticipated in women who receive conjugated estrogens plus medroxyprogesterone acetate as they acclimate to therapy, and this was not associated with hyperplasia.

Endometrial Hyperplasia↗
PubMed2004

Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial.

OBJECTIVE: To compare clinical outcomes after randomization to hysterectomy versus medical treatment in patients with chronic abnormal uterine bleeding refractory to medroxyprogesterone acetate. METHODS: We randomly assigned 63 premenopausal women with abnormal uterine bleeding refractory to cyclic medroxyprogesterone acetate treatment to receive either a hysterectomy or expanded medical treatment. Within each randomized group, the specific treatment approach was determined by patient and provider preference. The primary analysis compared changes in clinical outcomes at 6 and 24 months by using an intention-to-treat approach. Secondary as-treated analyses after adjustment for baseline covariates compared participants randomly assigned to medical treatment who continued the medical approach with those who crossed over to hysterectomy. RESULTS: The intention-to-treat analyses at 6 months revealed greater symptom improvement in the hysterectomy group than in the medicine group for pelvic pain (P <.01), urinary urgency (P =.03), incomplete bladder emptying (P =.03), breast pain (P =.02), and cessation of vaginal bleeding (87% versus 11%, P <.001). Seventeen of 32 women assigned to medicine (53%) eventually crossed over and received a hysterectomy, and by 24 months the statistically significant differences by intention-to-treat were limited to greater improvement in hot flushes (P <.01) and cessation of vaginal bleeding (P <.01). Within-group analyses at year 2 showed statistically significant improvements from baseline on most symptoms for women who had a hysterectomy, whether through randomization or crossover. Women remaining on medical treatments had statistically significant improvements in pelvic pain, pelvic/bladder pressure, and stress incontinence. In a nonrandomized comparison with women who remained on medical treatments through year 2, those crossing over to hysterectomy experienced greater improvements in bleeding (P <.01), pelvic pain (P <.01), low back pain (P =.02), breast pain (P =.01), urinary frequency (P =.01), and urgency (P =.02). However, they also experienced more days off from work or usual activities (P <.01) and more days spent in bed (P <.01) than those who remained on medicine. CONCLUSION: For patients with abnormal uterine bleeding refractory to medroxyprogesterone acetate, hysterectomy is superior to expanded efforts with oral medications for alleviating clinical symptoms but may lead to more days of restricted activity.

Adult↗
PubMed1981

Placental production of 5 beta-pregnane-3 alpha,20 alpha-diol in goats.

A major product of progesterone metabolism by the goat placenta in vitro was found to be 5 beta-pregnane-3 alpha,20 alpha-diol. The concentration of this steroid has been measured by radio-immunoassay in the peripheral circulation during pregnancy. Peripheral plasma concentrations of 5 beta-pregnane-3 alpha,20 alpha-diol were low (less than 6 nmol/l) in anoestrous and nonpregnant ovariectomized goats, and during the first month of pregnancy but increased progressively after day 45 of pregnancy, reaching 78-94 nmol/1 between days 112 and 142. Thereafter levels declined before term. Changes in the plasma concentration of 5 beta-pregnane-3 alpha,20 alpha-diol during pregnancy in the goat therefore resembled those of progesterone in the sheep. Plasma concentrations of 5 beta-pregnane-3 alpha,20 alpha-diol between day 70 and term were not influenced by repeated administration of medroxyprogesterone acetate from days 51 to 82 or by lutectomy in goats treated with medroxyprogesterone acetate. Secretion of 5 beta-pregnane-3 alpha,20 alpha-diol by the uterus and its contents was indicated by a positive venous-arterial difference across the uterus between days 128 and 141 in three ovariectomized pregnant goats receiving medroxyprogesterone acetate. Comparison of the rates of metabolism of progesterone by homogenates of placenta in vitro showed that the placental tissue from goats was three time more active in this respect than was tissue from sheep. The ratio of the plasma concentrations of 5 beta-pregnane-3 alpha,20 alpha-diol and progesterone in late pregnancy in ovariectomized or lutectomized goats exceeded by a factor of 10 that in sheep at a comparable stage of gestation. It is suggested that reductive metabolism of progesterone before it is secreted may account for the inability of the placenta to maintain pregnancy after ovariectomy in goats.

Animals↗
PubMed1984

Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins.

The pharmacokinetics of progesterone after oral administration were investigated. After a single dose of 100 mg, serum concentrations of progesterone around 50-60 nM and of 20 alpha-hydroxy-4-pregnene-3-one around 5-6 nM were recorded within 1-4 hours and elevated levels persisted for 8-12 hours. There were only minor changes in 17 alpha-hydroxyprogesterone concentrations and serum levels of androstenedione and cortisol were unaffected. A significant conversion of circulating progesterone into deoxy-corticosterone was demonstrated. During clinical treatment with oral progesterone the individual serum concentrations of this potent mineralocorticoid were closely correlated to the progesterone concentrations. This observation could be important as regards the etiology of certain clinical disorders characterized by fluid retention. According to competitive binding analyses there was no evidence that progesterone or medroxyprogesterone acetate could cause significant displacement of cortisol from corticosteroid-binding globulin during clinical treatment. The effects of natural and synthetic hormones upon subfractions of high density lipoprotein (HDL) cholesterol and liver proteins were followed in postmenopausal women during replacement therapy with various estrogen-progestogen combinations. The total serum cholesterol level was significantly reduced during treatment with all estrogen regimens. The concentrations of HDL cholesterol, HDL2 cholesterol, apolipoprotein A I and A II were increased in a dose-dependent pattern during unopposed estrogen therapy. The potency of 10 micrograms of ethinyl estradiol was estimated to be equivalent to 3-4 mg of estradiol valerate. Estrogen effects were significantly reversed by levonorgestrel 250 micrograms and also by medroxyprogesterone acetate 10 mg. During treatment with natural progesterone, no changes were recorded in HDL cholesterol or its subfractions. As compared with the lipoproteins, pregnancy zone protein and sex hormone binding globulin (SHBG) were found to be more sensitive to the alkylated than to the non-alkylated estrogen. Both levonorgestrel and medroxyprogesterone acetate clearly reduced SHBG levels after 3 months, whereas micronized progesterone had no such effect. While tamoxifen counteracted the therapeutic and metabolic effects of estrogen the sequential addition of estriol had no apparent influence. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effects were dose-dependent and no qualitative differences between ethinyl estradiol and estradiol valerate were recorded.

Administration, Oral↗
PubMed1992

Long-term transdermal estradiol therapy: effects on endometrial histology and bleeding patterns.

Sixty postmenopausal women were enrolled in a 2-year randomized unmasked trial to determine the long-term safety of estradiol (E2) administration by a transdermal therapeutic system. Group I subjects received 0.1 mg of transdermal E2 for 24.5 days of each 28-day cycle for 96 weeks. Group II subjects received the same dosage of transdermal E2 plus 10 mg of medroxyprogesterone acetate, given orally from days 13-25 of each cycle. Vaginal bleeding patterns and endometrial histology were characterized. The subjects recorded bleeding patterns daily. Endometrial biopsies were performed during scheduled follow-up visits at 48 and 96 weeks or as needed to evaluate abnormal bleeding. Data were analyzed by intention to treat. Ten and four subjects dropped out of the study from groups I and II, respectively. A total of 575 and 627 treatment cycles were observed in the same respective groups. Vaginal bleeding was observed in 980 cycles: 381 of 575 cycles in group I (66.3%) and 599 of 627 cycles in group II (95.5%). Bleeding onset, duration, and quantity were similar for both groups. The incidence of hyperplasia was 42 and 4% for groups I and II, respectively, over the 96-week study period. All cases of hyperplasia in group I were treated with sequential medroxyprogesterone acetate for 12 weeks, followed by rebiopsy. In ten of 11 cases, the progestin therapy converted the hyperplasia to a normal endometrium. In one case, the endometrium became hyperplastic again at 96 weeks, but reverted to normal with 12 weeks of medroxyprogesterone acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1990

[Postmenopausal women: changes in plasma lipids with different estrogen replacement therapies].

We measured total, HDL and LDL cholesterol and triglycerides in 183 postmenopausal women before and 4 weeks after hormone therapy. Ethinyl estradiol or conjugated estrogens alone or in association with medroxyprogesterone, norethyndrone or norgestrel were used in different dosages either continuously or sequentially. Total cholesterol decreased from 206 to 196 mg/dl and HDL raised from 47 to 53 mg/dl (p less than 0.001) except in the group treated with estradiol-levonorgestrel in which HDL fell from 41 to 36 mg/dl (p less than 0.001). HDL cholesterol decreased from 133 to 113 mg/dl, overall. The total cholesterol/HDL ratio decreased from 4.8 to 4.2 in all groups except the group previously mentioned. Estrogen therapy, isolated or in association to medroxyprogesterone induced a moderate increase in serum triglyceride levels (132 to 149 mg/dl, p less than 0.001). Thus, the administration of estrogens in postmenopausal women is associated with a decrease in total, LDL and total/HDL cholesterol ratio and an increase in triglycerides. Norgestrel but not medroxyprogesterone partially revert these effects.

Adult↗
PubMed1995

[Positive and negative effects of progestins on platelet-activating factor acetylhydrolase activity in rat plasma].

Platelet-activating factor acetylhydrolase (PAF-AH), the enzyme that inactivates PAF, is regulated by steroid hormones including progestin. It has been reported that 17 alpha-ethynylestradiol decreases plasma PAF-AH activity and medroxyprogesterone increases the enzyme activity. In this study, we elucidated the effects of various progestins on plasma PAF-AH activity and lipoprotein cholesterol levels. Plasma PAF-AH activity in female adult rats treated with either progesterone or 17 alpha-hydroxyprogesterone (50mg/kg, 3 days) did not change significantly. Both medroxyprogesterone and megestrol acetate (50mg/kg, 3 days) significantly increased plasma PAF-AH activity, but both norethindrone acetate and norethynodrel (50mg/kg, 3 days) significantly decreased the enzyme activity. In addition, not only did medroxyprogesterone increase plasma PAF-AH activity but plasma lipoprotein cholesterol and norethindrone acetate decreased both of them. A significant correlation between plasma PAF-AH activity and the lipoprotein level was found (r = 0.974, p < 0.01). When PAF (10nmol/kg) was administered to female adult rats pretreated with progestins, the mortality of the rats that had low plasma PAF-AH activity due to norethindrone acetate was increased in the same manner as observed in the 17 alpha-ethynylestradiol-pretreated group. These findings indicate that progestins have various effects on plasma PAF-AH activity and the lipoprotein level. In addition, some progestins, which have an estrogenic effect on enzyme activity, may be related to the thrombotic episodes observed in oral contraceptive users.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Establishment and characterization of in vitro decidualization in normal human endometrial stromal cells.

We established and characterized a novel experimental model of in vitro decidualization in normal human endometrial stromal cells. In a comparison of decidualization induction, 8-Br-cAMP showed the strongest ability to induce decidualization in stromal cells among four inducers examined: progesterone, medroxyprogesterone acetate, prostaglandin E2, and 8-Br-cAMP. The effects of 8-Br-cAMP were enhanced by prostaglandin E2 but not altered by medroxyprogesterone acetate. Both progesterone and medroxyprogesterone acetate activity was so weak that it took more than 2 weeks to induce in vitro decidualization. These results suggest that there are two independent decidualization signals in the in vitro decidualization, a cAMP-mediated signaling pathway and a progesterone receptor-mediated signaling pathway, and that cAMP-inducers are major factors in decidualization in vivo. Differential expressions of three membrane aminopeptidases on the stromal cells during the decidualization are also discussed.

Cells, Cultured↗
PubMed1990

High progesterone receptor concentration in a variant of the ZR-75-1 human breast cancer cell line adapted to growth in oestrogen free conditions.

Culture of ZR-75-1 human breast cancer cells for 5 days in the absence of oestrogens (phenol red-free medium supplemented with dextran coated charcoal stripped 5% fetal calf serum) resulted in a slowing of growth rate and loss of progesterone receptors. Oestradiol at 10(-9) M markedly stimulated growth and progesterone receptor synthesis over a 5-day period. While medroxyprogesterone acetate (10(-10) to 10(-6) M) inhibited growth of ZR-75-1 cells growing in complete medium, in the short-term absence of oestrogens low concentrations were growth stimulatory. Cells deprived of oestrogens for 5 days retained sensitivity to growth inhibition by 4-hydroxy tamoxifen. ZR-75-1 cells were also adapted to growth in the absence of oestrogens over a 5-month period. These cells (ZR-PR-LT) failed to express binding sites characteristic of the type 1 oestrogen receptor but progesterone receptor expression was at a level normally associated with oestrogen induction. Adapted cells were growth inhibited by oestradiol, 4-hydroxy tamoxifen and medroxyprogesterone acetate, but despite elevated progesterone receptor expression the progestin was only marginally more inhibitory than in the parent line. Our data indicate a poor quantitative relationship between response to progestins in vitro and progesterone receptor concentration and support previous findings that acquisition of an oestrogen independent phenotype does not necessarily result in resistance to anti-oestrogens.

Antineoplastic Agents↗
PubMed1990

Regulation of collagenase production by steroids in uterine smooth muscle cells: an enzymatic and immunologic study.

An enzyme-linked immunosorbent assay (ELISA) has been developed for rat collagenase. The assay is capable of measuring the enzyme from a variety of rat cell sources at concentrations of 10-50 ng/ml, approximately 500-1,000-fold more sensitive than radiolabelled collagen fibril assay systems. The assay is specific to collagenase from the rat: enzymes from human, tadpole, mouse, and bacterial sources failed to cross-react significantly with rat enzyme. The assay is reproducible and accurate, and is capable of detecting enzyme in the presence of serum or tissue inhibitors. Using the ELISA, we have examined the effect of a variety of hormones on the production of collagenase by rat myometrial smooth muscle cells in culture. Of all the reproductive hormones examined, only progesterone and its synthetic derivative medroxyprogesterone acetate were capable of inhibiting the production of the enzyme by these cells. The maximally effective concentration of progesterone was 1 x 10(-6)M, and that of medroxyprogesterone acetate was 1 x 10(-7)M. The effect of the steroid was selective: no effect on cell proliferation or on general protein synthesis was observed. In addition to the progestational steroids, the glucocorticoids were also capable of inhibiting the production of collagenase by the cells at similar nominal concentrations. However, the myometrial cells were found actively to metabolize progesterone but not hydrocortisone in culture. Thus, the effective inhibitory concentration of progesterone was approximately ten-fold lower than that of hydrocortisone. The results of this study support the concept that progesterone plays a major role in preventing the production of collagenase in the rat uterus.

Animals↗
PubMed1985

Pharmacokinetic and pharmacodynamic investigations with monthly injectable contraceptive preparations.

Eight normally menstruating women received Cycloprovera (25 mg medroxyprogesterone acetate with 5 mg estradiol cypionate) and seven other volunteers received HRP-102 (50 mg norethisterone enanthate with 5 mg estradiol valerate) injections at 30-day intervals for three consecutive months. The peripheral plasma levels of estradiol (E2), progesterone (PROG), medroxyprogesterone acetate (MPA) and norethisterone (NET) were measured in the luteal phase of a pretreatment cycle, during the third treatment month and during a subsequent recovery period of 60 days. Blood samples were drawn three times a week (Mondays, Wednesdays and Fridays) and endometrial biopsies were taken on day 20 to 26 of the pretreatment cycle, 20 to 24 days after the last injection and 20 to 24 days after the first normal menstrual-like bleeding during the recovery period. The (geometric) mean maximum level of MPA was 2.9 (2.4-3.7) nmol/1 and that of NET 10.1 (6.4-15.8) nmol/l. Thirty days after the last injection, the MPA level was 0.72 (0.46-1.1) nmol/l and that of NET 1.7 (1.2-2.3) nmol/l. The maximum level of exogenous E2 was 890 (700-1130) pmol/l after Cycloprovera and 1570 (870-2820) pmol/l after HRP-102 administration. Forty-nine and 41 days, respectively, after the last injection, a broad (endogenous) E2 peak was observed in all subjects, which was not followed by an ovulatory rise in PROG levels. The first ovulatory rise in PROG occurred between 71 and 90 days after the last Cycloprovera and 59 to 87 days after the last HRP-102 injection. One subject in each of the two groups failed to ovulate during the 90-day post injection period. Dating and morphometric analysis of the endometrial biopsy specimens obtained 20 to 24 days after the last injection revealed that the suppressive effect of Cycloprovera was stronger than that of HRP-102. Each injection of both formulations was followed by a bleeding-free period of approximately two weeks. The percentage of days with bleeding and spotting was 24% for Cycloprovera and 29% for HRP-102. It is concluded, that both monthly injectables inhibit follicle maturation for some 30 days and ovulation and corpus luteum formation for some 60 days, providing thus a considerable margin of safety in terms of the expected duration of contraceptive protection.

Adult↗
PubMed1987

A multicentered pharmacokinetic, pharmacodynamic study of once-a-month injectable contraceptives. I. Different doses of HRP112 and of DepoProvera. World Health Organization Task Force on Long-acting Systemic Agents for Fertility Regulation.

A multicentered study was undertaken at three institutions in Hungary, Mexico and Thailand in women of reproductive age to evaluate the effects of full and half doses of HRP112 (depot-medroxyprogesterone acetate (DMPA) plus estradiol cypionate) and DMPA alone on ovarian function, bleeding patterns and HDL-cholesterol levels. Full dose HRP112 contained 25mg DMPA plus 5mg, of estradiol cypionate and the half dose, 12.5mg DMPA plus 2.5mg of estradiol cypionate. The full and half dose DMPA were 25 and 12.5mg respectively. In all, 88 women were recruited in the study and randomized within each centre, to the four treatment groups. Subjects were studied for a control cycle, three one-month injection intervals and followed-up for a further two months. Serum concentrations of estradiol, progesterone and medroxyprogesterone acetate were determined three times a week during the third injection interval and during the two months of follow-up. While the results from all centres indicated that the four preparations were all effective in inhibiting ovulation for at least one month, there were marked between centre differences in pharmacokinetic profiles. More regular bleeding patterns were observed in women who received the estrogen-progestogen combination preparations than in those who received DMPA alone.

Adolescent↗
PubMed1989

Aggression, physical activity levels and sex role identity in teenagers exposed in utero to MPA.

Sex-dimorphic traits and behavior were measured in a 17-year old prospective study of 74 teenager boys and 98 girls who had been exposed to medroxyprogesterone acetate in utero compared with 459 boys and 546 girls not exposed. Bem Sex Role Identity scores were identical in exposed and non-exposed teenagers of each sex. There were no significant differences between MPA-exposed and non-exposed males or females on the Buss-Durkee overall aggression scale and on its assaultiveness subscale. Mothers of exposed males more often reported that teachers had complained that their offspring were naughty in school. No such difference was reported for females, nor for other school behaviors of dominance/aggression, activity, shyness and quietness. Exposed and non-exposed children were similar in the number of accidents experienced in childhood, as reported by their mothers, and in participation in competitive sports. These findings fail to support hypotheses posed by earlier researchers that exposure in utero to medroxyprogesterone acetate might alter sex-dimorphic behavior or traits in later life.

Adolescent↗
PubMed1984

Modification of juvenile play and other social behaviour in the rat by neonatal progestins: further studies.

The effects of altering neonatal levels of progestins on the later development of social play behaviour was studied. Progestin levels were raised in experiment one by administering injections of either progesterone or medroxyprogesterone acetate. This indicated that exposure to either hormone led to reduced levels of social play in juvenile rats of both sexes, confirming earlier reports of lowered levels of play following medroxyprogesterone obtained via maternal milk. In Experiment 2, endogenous progestin levels were lowered by administration of the antiserum to progesterone. The prediction that this should result in raised levels of juvenile play was supported for males, but not for females. Females in Experiment 2 by contrast showed a decrease in play. Possible reasons for this sex difference in response to progesterone antiserum are discussed.

Animals↗
PubMed1977

The in vivo metabolism of progestins. IV. The metabolic clearance rate and plasma binding of 6alpha-methylpregn-4-ene-3, 20-dione in women.

[3H]6alpha-methylprogesterone (6MP) was synthesized by selective catalytic tritiation of the delta1-olefinic bond of 6alpha-methylpregna-1,4-diene-3,20-dione. The metabolic clearance rate of 6MP (MCR6MP) was determined in 6 women by the single injection technique. The plasma MCR6MP was 4047 +/- 298 L/day (59 +/- 15 L/day/kg) which was higher than the MCR of progesterone and medroxyprogesterone acetate (6alpha-methyl-17alpha-hydroxy-pregna-4-ene-3,20-dione acetate). The high clearance was not due to binding or metabolism of 6MP by red cells. Although 6MP was bound to CBG with a lower affinity than progesterone, this could not entirely explain the high MCR6MP. When considered with the reports of progesterone and medroxyprogesterone acetate clearance, the present studies suggest that the 6alpha-substitution of progesterone leads to an increased rate of steroid metabolism in women.

Carrier Proteins↗
PubMed1985

Infarction-nephrectomy for metastatic renal carcinoma. Southwest oncology group study.

Thirty patients with metastatic renal cell cancer were treated by renal infarction, followed by delayed nephrectomy. All cases were collected over an eighteen-month period, with a minimum follow-up of one year. There were no complete remissions and only one partial remission, which lasted twenty-one months before progression of disease. Three patients had stable disease for at least six months, but eventually all patients showed evidence of progression. After tumor progression was documented patients were treated with intramuscular medroxyprogesterone acetate (Depo-Provera) 800 mg per week. No patient responded to this therapy. Overall, a 28 per cent one-year survival and a seven-month median survival were realized, which is similar to other series in which no therapy or palliative nephrectomy was performed. We conclude that infarction and nephrectomy is not an effective modality in the treatment of metastatic renal cell carcinoma. In addition, medroxyprogesterone was not shown to be significantly active against renal cancer in this study.

Carcinoma, Renal Cell↗
PubMed1984

Diamine oxidase activity in human decidua and endometrium.

The activity of diamine oxidase, the enzyme that catalyzes the oxidative deamination of putrescine, spermidine, histamine, and other substances involved in the regulation of cell proliferation and immune responses, increases up to 1000-fold in blood of pregnant women. In vivo experiments have shown that progestins stimulate diamine oxidase in the rodent uterus. We examined diamine oxidase activity in human endometrium at different phases of the menstrual cycle and in decidua from first-trimester pregnancies. Enzyme activity was also assayed in tissues and media of cultured human endometrium and decidua in the presence of estradiol or medroxyprogesterone acetate. Enzyme activity in first-trimester decidual tissues (286 +/- 86 mU of diamine oxidase per milligram of DNA; mean +/- SEM) was considerably higher (p less than 0.001) than that in endometrium (2.6 +/- 1.6), and the activity increased from 6 to 17 weeks of pregnancy. No significant differences were detected in proliferative and secretory endometrium. Activities in media of endometrium in organ culture generally were below detectability. Decidua secreted large amounts of the enzyme into the medium (160 to 600 mU per milligram of DNA per day), greatly exceeding the initial tissue activities. Bovine serum, when added to culture media, caused a marked increase in diamine oxidase levels, whereas estradiol (10(-8) mol/L) or medroxyprogesterone acetate (10(-6) mol/L) did not. Kinetic analysis showed a Michaelis constant of 7.4 X 10(-6) mol/L with putrescine as the substrate. Spermidine and histamine were competitive inhibitors of putrescine with an inhibition constant of 1.1 X 10(-4) and 3.5 X 10(-6) mol/L, respectively. These results demonstrate synthesis and export of diamine oxidase by decidua in organ culture, stimulation of activity by serum factors, and competition of histamine, spermidine, and putrescine for the enzyme.

Amine Oxidase (Copper-Containing)↗

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