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At least 19 recordsLinked to original sources
PubMed2000

Ovulation suppression for endometriosis.

BACKGROUND: Although the etiology of endometriosis is unknown, several theories exist, the most popular of which is retrograde menstruation. As endometriosis can only be diagnosed by laparoscopy, neither the incidence (annual occurrence) nor the prevalence (proportion of the population affected) of endometriosis is known. The association between endometriosis and infertility isn't clear in Stage I (minimal) and Stage II (mild) endometriosis. Endometriosis appears to be an estrogen dependent condition. At the time of menopause, most endometriosis becomes quiescent. This hormonal dependency prompted researchers to seek agents which would suppress ovarian activity. OBJECTIVES: To determine effectiveness of a) ovulation suppression with danazol, medroxy progesterone acetate, gestrinone, combined oral contraceptive pills and GnRH analogues versus placebo or no treatment and b) any of the above agents versus danazol, for the treatment of endometriosis explained infertility in terms of clinical pregnancy rate. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: Four RCTs with five treatment arms compared an ovulation suppression agent with placebo or no treatment. Eight trials were identified comparing a suppressive agent with danazol. DATA COLLECTION AND ANALYSIS DATA EXTRACTION: A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. MAIN RESULTS: The common odds ratio for pregnancy following ovulation suppression versus placebo or no treatment was 0.83 (95% CI 0.5-1.39). These data were statistically homogeneous although clinical heterogeneity was present. Their consistency in showing no treatment benefit suggests that this group of interventions is ineffective. Common odds ratio for pregnancy following all agents versus danazol was 1.20 (95% CI 0. 85-1.68). Again these data were homogeneous and suggest no significant treatment benefit in terms of pregnancy rate. REVIEWER'S CONCLUSIONS: Given the significant period of amenorrhea associated with ovulation suppression, the lack of treatment benefit demonstrated and the adverse effects commonly associated with these treatments, ovulation suppression cannot be recommended as a standard therapy for endometriosis-associated infertility.

Danazol↗
PubMed1992

A comparison of ovulation suppression and ovulation stimulation in the treatment of endometriosis-associated infertility.

This study compares ovulation stimulation or suppression with the pregnancy rate among infertile couples with endometriosis. The design is a nonrandomized, prospective, multicentered cohort analytic study. Two hundred and ninety-seven couples with laparoscopy-proven endometriosis were analyzed: 68 received no therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%) conceived and pregnancy rates were similar in each treatment group. The relative likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits 1.2-7.1); the relative likelihood of pregnancy with danazol was 1.02 (95% confidence limits 0.5-2.3). This study suggests that pregnancy rates during clomiphene treatment could be superior to expectant therapy, while pregnancy rate after danazol is similar to no treatment.

Adult↗
PubMed2004

Pharmacokinetics, ovulation suppression and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera.

Depo-Provera is a highly effective contraceptive, given intramuscularly (150 mg/mL) once every 3 months. It has been in use in the United States for over 10 years. A new lower-dose formulation of Depo-Provera (104 mg/0.65 mL), has been developed that allows subcutaneous injection, potentially increasing the convenience, ease of administration and tolerability of this contraceptive. This prospective, randomized, single-center, single-dose trial evaluates the pharmacokinetics of the lower-dose formulation of Depo-Provera and compares the lower-dose formulation to the original formulation with regard to efficacy and duration of ovulation suppression and the return to ovulation at 12 months. While delivering a 30% lower total dose than the intramuscular formulation, the lower-dose formulation of Depo-Provera suppressed ovulation for more than 13 weeks in all subjects and was not affected by body mass index or race. Median time for return to ovulation was 30 weeks, with a 97.4% cumulative rate of return to ovulation at 12 months.

Adolescent↗
PubMed1998

Duration of ovulation suppression with subcutaneous silicone implants containing norgestomet in Bos indicus heifers and cows.

The aim of this study is to determine the duration of suppressing oestrus or ovulation in Bos indicus heifers and cows using norgestomet (N) incorporated into a silicone implant. Twelve heifers and 18 cows undergoing oestrous cycles were allocated to one of two treatment groups (6 heifers and 9 cows per group). Animals were treated with a single subcutaneous (s.c.) silicone implant containing 3 mg of N or two identical silicone implants (6 mg of N in two silicone implants) on day 0 of the study. An analogue of prostaglandin F2-alpha was administered intramuscularly, to all animals on days 0 and 6 to induce regression of corpora lutea. Implants were removed from all animals on day 21. Animals were observed for signs of behavioural oestrus while implants were in situ and for 6 d following implant removal. Blood samples were collected on alternate days from day 0 to 20 and again on day 21 and analysed for plasma progesterone (P4). Transrectal ultrasonography was performed on days 0, 6, 10, 14, 18, 21, 24, 26,27, and along with concentration of P4 in plasma was used to confirm ovulation during the treatment period. The cumulative percentages of animals ovulating during the 21 days implants were in situ were 6.7% (3 mg of N in one silicone implant) and 0% (6 mg of N in two silicone implants)Intervals from implant removal to oestrus (mean +/- S.E.M.) did not differ significantly among animals treated with either 3 or 6 mg of N in silicone implants (46.8 +/- 7.0 vs. 55.4 +/- 7.1 h, P = 0.398). Variances in interval from implant removal to oestrus among animals treated with 3 or 6 mg of N in silicone implants were also homogeneous (P = 0.942). The mean diameter of the ovulatory follicle on day 21 was larger in the animals treated with 3 mg of N compared to animals treated with 6 mg of N in two silicone implants ( 13.1 +/- 0.8 vs. 9.7 +/- 0.7 mm, P = 0.005). We conclude that treatment with 3 mg of N in a silicone implant will suppress ovulation in Bos indicus heifers and most cows for 21 d. Six mg of N in two silicone implants will suppress ovulation for 21 d in both cows and heifers.

Animals↗
PubMed2002

Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomized control trial of 2 and 5 mg per day for 120 days.

Daily administration of progesterone (P) antagonists to women inhibits ovulation and disrupts endometrial function. In this double-blind randomized trial, we have explored the contraceptive potential of two doses of the P antagonist mifepristone in healthy volunteers in Edinburgh and Shanghai. Ninety-eight women (58 in Edinburgh and 40 in Shanghai) were randomized to receive either 2 or 5 mg mifepristone daily for 120 d. Ovarian activity was monitored by the weekly measurement of steroid metabolites in urine and of E2 and P in plasma every month. Endometrial function was assessed by menstrual records, and ultrasound measurement of endometrial thickness was assessed every month. Endometrial biopsy was collected on d 12 of the control cycle and after 60 and 120 d of treatment. Ninety women (50 in Edinburgh and 40 in Shanghai) completed the study. Follicular activity continued during treatment with both doses in Edinburgh women, although ovulation was suppressed in the majority of cycles (90 and 95% of cycles in 2- and 5-mg groups, respectively). The women in Shanghai showed evidence of ovulation in only 3 of 160 months of treatment (2 in 2-mg group and 1 in 5-mg group). The majority of women in both centers were amenorrheic (65% in 2-mg group and 88% in 5-mg group in Edinburgh, and 90% in both dose groups in Shanghai). The endometrial thickness increased significantly in women in Edinburgh and decreased in Shanghai; histology showed either atrophic or cystic changes without evidence of hyperplasia. There was no pregnancy reported in the 200 months of exposure in 50 sexually active women who had used no other method of contraception during the study. We conclude that mifepristone in low daily doses inhibits ovulation and induces amenorrhea in the majority of women and has the potential to be developed as a novel estrogen- free oral contraceptive pill.

Adult↗
PubMed1988

Inhibitors of mammalian tissue collagenase and metalloproteinases suppress ovulation in the perfused rat ovary.

We have examined the effects of a new synthetic inhibitor of mammalian tissue collagenase, CI-1 (N-[3-N-(benzyloxycarbonyl)amino-1-(R)carboxypropyl]L-leucyl-O-methyl-L- tyrosine N-methylamide; G. D. Searle SC 40827), and a general metalloproteinase inhibitor, 1,10-phenanthroline, on ovulation, as judged by the observation of follicular rupture, and on progesterone production of the perfused rat ovary. Ovaries of PMSG (20 IU)-primed rats were perfused for 21 h, and samples of medium were taken for analysis of progesterone concentration. The number of ovulations was estimated by counting the number of oocytes released into the perfusion chamber. Ovaries were stimulated with LH (0.1 micrograms/ml) plus 3-isobutyl-1-methylxanthine (IBMX; 0.2 mM), and this treatment resulted in a mean of 17.2 ovulations/treated ovary. 1,10-Phenanthroline dose-dependently inhibited ovulation, with 0, 0.2, and 12.5 ovulations/treated ovary at 1.0, 0.1, and 0.01 mM, respectively. This inhibition of ovulation closely paralleled the inhibition of extracted collagenase from uterus and ovary. However, 1,10-phenanthroline also suppressed progesterone release in a dose-dependent manner. Addition of the collagenase inhibitor (CI-1; 25 microM) 1 h after LH plus IBMX inhibited ovulation (6.3 ovulations/treated ovary). Its relatively inactive stereoisomer (CI-2; 25 microM) did not suppress ovulation (20.0 ovulations/treated ovary). CI-1 inhibited extracted uterine collagenase 50% at a concentration of 2 microM, whereas CI-2 was only 1/15th as effective. There was an 80% loss of CI-1 from the medium during the perfusions. Neither CI-1 nor CI-2 had any effect on LH plus IBMX-stimulated progesterone release. These data demonstrate that the general metalloproteinase inhibitor 1,10-phenanthroline is able to inhibit ovulation, but also inhibits steroidogenesis. The more specific inhibitor of collagenase, CI-1, can inhibit ovulation without affecting steroid production. These data indicate an important role for collagenase in the ovulatory process.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Gonadotropin-releasing hormone agonist suppresses ovulation, menses, and endometriosis in monkeys: an individualized, intermittent regimen.

This study was designed to test the efficacy of a long-acting GnRH agonist (alpha) for inhibition of ovulation and menses in monkeys as well as suppression of mild to moderate endometriosis through an individualized, intermittent regimen. Endometriosis was surgically induced in 21 cynomolgus monkeys; ectopic tissue viability was verified histologically. GnRH alpha (leuprolide, D-Leu6-Pro9-Net-LHRH, Abbott Laboratories) was injected weekly in treatment cycle 1 (10 microgram/kg, sc; n = 15). Ovulation and menses ceased in 6 of 15 females. For the remaining 9 monkeys, the GnRH alpha dose was increased to 15 microgram/kg weekly in treatment cycle 2. Still, 4 monkeys resisted suppression; in treatment cycle 3, their regimen increased to 15 microgram/kg every fourth day. Thus, anovulation and amenorrhea was achieved in 14 of 15 monkeys within 90 days, seemingly as a result of ovarian desensitization, since GnRH alpha injections usually enhanced serum LH and FSH levels (P less than 0.05). Frequent laparotomies and daily hormonal profiles of estradiol, progesterone, FSH, and LH in serum confirmed these findings. After treatment, 12 of 15 monkeys manifested resolution of ectopic endometrial tissue; concurrently, there was no change in the severity of endometriosis in the 6 saline-injected controls. Six of 15 monkeys became pregnant within 90 days after cessation of GnRH alpha injections; 1 of 6 control females conceived. These findings may encourage consideration of clinical investigations employing individualized and/or intermittent GnRH alpha administration for the treatment of endometriosis or to achieve contraception.

Animals↗
PubMed1998

Bestatin, an aminopeptidase inhibitor, promotes follicular growth and ovulation suppressed by stress in mice.

We previously reported that the intraperitoneal and intrabursal administration of bestatin, an aminopeptidase inhibitor, enhanced follicular growth and ovulation in immature mice. In this study, we examined the effect of bestatin on follicular growth and ovulation under the conditions in which the ovarian response to gonadotropins was suppressed. Immature female mice were exposed to 72-h continuous lighting (on days 20-22 of life), or to 24-h starvation (on day 20). On days 20-22, bestatin (4 mg/ml, 100 microl) or PBS (100 microl) was administered ip. 4 times and pregnant mare serum gonadotropin (PMSG, 5 IU) and hCG (5 IU) were given on days 21 and 23, respectively. The numbers of ovulated oocytes per mice were significantly attenuated by both stresses. Bestatin significantly enhanced the numbers of ovulated oocytes under both lighting (49.5+/-7.0 vs. 28.0+/-5.5) and starvation (28.6+/-2.6 vs. 20.2+/-2.0) stresses (with vs. without bestatin, P<0.05). When follicular development was stimulated by PMSG (20 IU) on day 21, the serum estradiol concentration on day 23 was also suppressed by both stresses, but enhanced by bestatin under lighting (231.3+/-36.0 vs. 111.0+/-23.0 pg/ml) and starvation (151.9+/-8.8 vs. 90.7+/-15.4 pg/ml) stresses (with vs. without bestatin, P<0.01). Northern blot analysis revealed that the expression of P450arom-mRNA in the ovaries induced by PMSG (20 IU) was increased on day 23 by treatment with bestatin under starvation stress. These results indicated that stress inhibited the ovarian response to gonadotropins and that bestatin restored the response suppressed by stress.

Aminopeptidases↗
PubMed2005

Ovulation suppression of premenstrual symptoms using oral contraceptives.

Managing premenstrual symptoms at the most fundamental level necessitates careful consideration of female reproductive biology. Inhibiting ovulation using hormonal agents is a reasonable approach for reducing premenstrual symptoms, but the benefits of agents such as gonadotropin-releasing hormone agonists and the synthetic androgen danazol are largely offset by their adverse effects and costs. Combination oral contraceptives provide an alternative that is widely accepted by women experiencing premenstrual symptoms and by their physicians; and newer formulations with lower levels of estrogen and progestin, administered using a monthly regimen with a shortened pill-free interval, appear promising for alleviating patient distress from severe premenstrual symptoms.

Adolescent↗
PubMed1987

Occurrence of pregnancy despite spontaneous ovulation suppression by intracerebroventricular infusion of substance P in rats.

Substance P (SP) infusion into the third cerebral ventricle and intraperitoneal injection of pentobarbital block spontaneous ovulation in female rats. This paper presents a study on the effect of SP intracerebroventricular infusion on the occurrence of copulation-induced ovulation. Spontaneous ovulation in female rats was blocked either by SP infusion into the third cerebral ventricle or by intraperitoneal injection of pentobarbital on the day of proestrus. Female rats infused with 20 nmol of SP in 10 microliter and then left with fertile males on the night of proestrus were found to be pregnant in 90% of cases, similarly as in the control group (86%). The lowest percentage of pregnancies was found in the group of animals injected with pentobarbital (69%). The obtained results suggest that reflex ovulation in female rats induced by copulation cannot be blocked by SP i. c. v. administration nor by i. p. pentobarbital, and suggest a different neural mechanism responsible for spontaneous and copulation-induced reflex ovulation.

Animals↗
PubMed1986

Chronic gonadotropin-releasing hormone agonist treatment suppresses ovulation and sexual behavior in group-living female rhesus monkeys.

The sexual behavior of six adult rhesus females was observed with each of four males prior to, during, and following a 90 day treatment with 20 micrograms/day of a gonadotropin releasing-hormone (GnRH) agonist (WY-40972). All females ovulated, approached males and copulated during an untreated cycle. No ovulations occurred during agonist treatment and all females showed reduced sexual interest during the last 25 treatment days. Three females showed elevated estradiol and copulated during the first 10 days of agonist treatment, but never showed similar levels of estradiol or copulation during the rest of treatment. Within 34 days after agonist treatment, all females initiated proximity to males, copulated, and ovulated. All females became pregnant on their second ovulation after agonist treatment. This demonstration that inhibition of ovulation with a GnRH agonist decreased rhesus female sexual initiation, demonstrates the importance of ovarian hormones to female sexual motivation and suggests that the changes in human female sexual interest should be evaluated during the development of agonist-based contraceptives.

Animals↗