The cardiometabolic effect of current management of polycystic ovary syndrome: strategies of prevention and treatment.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder amongst women of reproductive age, which is characterized by reproductive and cardiometabolic disturbances with long-term health repercussions. Insulin resistance (IR), impaired glucose tolerance, type 2 diabetes mellitus (DM2), obesity and dyslipidemia occur more in women with PCOS than in age-comparable women without PCOS. Long term data regarding risks or benefits of medical intervention for metabolic dysfunction of PCOS are lacking. Therapies, such as oral contraceptives (OCPs) and anti-androgenic medications used to manage the reproductive manifestations of PCOS, may themselves be the cause of cardiometabolic perturbations. Hence, strategies regarding the management of reproductive issues in PCOS encompass a patient-specific tailored approach. Factors that influence the cardiometabolic side effects arising during treatment of the reproductive manifestations of PCOS (hirsutism/anovulation) are also discussed in this paper in order to build future strategies to minimize the overall cardiometabolic risk.

Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in rat.

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients. Here, we found that 3 weeks of rutin (a novel compound for BAT activation) treatment increased BAT activation, thereby it improved thermogenesis and systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat. In addition, the expression levels of ovarian steroidogenic enzymes such as P450C17, aromatase, 3ß-HSD, 17ß-HSD and STAR were up-regulated in rutin-treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing hormone were normalized, and a large number of mature ovulated follicle with a reduction of cystic formation were observed in PCOS rat after rutin treatment. Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS rat. Collectively, our results indicate that rutin treatment significantly improves systemic insulin resistance and ovarian malfunction in PCOS, and our findings in this study provide a novel therapeutic option for the treatment of PCOS by activating BAT with rutin.

Dietary fat intake and reproductive hormone concentrations and ovulation in regularly menstruating women.

BACKGROUND: Emerging evidence suggests potential links between some dietary fatty acids and improved fertility, because specific fatty acids may affect prostaglandin synthesis and steroidogenesis. OBJECTIVE: The objective of this exploratory study was to evaluate associations between total and specific types of dietary fat intake and 1) hormone concentrations and 2) the risk of sporadic anovulation in a cohort of 259 regularly menstruating women in the BioCycle Study. DESIGN: Endogenous reproductive hormones were measured up to 8 times/cycle for up to 2 cycles, with visits scheduled with the use of fertility monitors. Dietary intake was assessed with up to four 24-h recalls/cycle. Linear mixed models and generalized linear models were used to evaluate the associations between dietary fatty acids and both reproductive hormone concentrations and ovulatory status. All models were adjusted for total energy intake, age, body mass index, and race. RESULTS: Relative to the lowest levels of percentage of energy from total fat, the highest tertile was associated with increased total and free testosterone concentrations (total: percentage change of 4.0%; 95% CI: 0.7%, 7.3%; free: percentage change of 4.1%; 95% CI: 0.5%, 7.7%). In particular, the percentage of energy from polyunsaturated fatty acids (PUFAs) in the highest tertile was associated with increases in total and free testosterone (total: percentage change of 3.7%; 95% CI: 0.6%, 6.8%; free: percentage change of 4.0%; 95% CI: 0.5%, 7.5%). The PUFA docosapentaenoic acid (22:5n-3) was not significantly associated with testosterone concentrations (P-trend = 0.86 in energy substitution models) but was associated with increased progesterone and a reduced risk of anovulation (highest tertile compared with the lowest tertile: RR: 0.42; 95% CI: 0.18, 0.95). Fat intakes were not associated with other reproductive hormone concentrations. CONCLUSIONS: These results indicate that total fat intake, and PUFA intake in particular, is associated with very small increases in testosterone concentrations in healthy women and that increased docosapentaenoic acid was associated with a lower risk of anovulation.

Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women.

STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. PARTICIPANTS, SETTING, METHODS: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. LIMITATIONS, REASONS FOR CAUTION: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose.

The impact of dietary folate intake on reproductive function in premenopausal women: a prospective cohort study.

BACKGROUND: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women. METHODOLOGY/PRINCIPAL FINDINGS: The BioCycle study (2005-2007) prospectively followed 259 healthy women aged 18-44 years from the western New York region for up to 2 menstrual cycles. Total folate and specific sources of folate were assessed up to 4 times per cycle by 24-hour recall. Estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured in serum up to 8 times per cycle, timed using fertility monitors. Anovulation was defined as a cycle with peak progesterone concentration ≤ 5 ng/mL and no LH peak in the mid/late luteal phase. Higher intake of dietary folate (in dietary equivalents) across tertiles had a marginally significant association with greater luteal progesterone levels (P trend 0.08). Higher intake of synthetic folate was significantly associated with higher luteal progesterone levels (P trend 0.05). Specifically, women in the 3(rd) tertile of synthetic folate intake had, on average, 16.0% (95% CI, 0.5-33.8%) higher luteal progesterone levels compared to women in the 1(st) tertile. Moreover, consumption of synthetic folate was significantly and inversely associated with anovulation such that women in the 3(rd) tertile had a 64% (95% CI, 8-86%) decreased odds of anovulation compared to the women in the 1(st) tertile (P trend 0.03). CONCLUSIONS/SIGNIFICANCE: These findings suggest that a diet high in synthetic folate may be associated with increased progesterone levels and lower risk of sporadic anovulation. Further study of the effect of dietary folate and folic acid supplement use on reproductive health is warranted.

Involvement of GDF-9, leptin, and IGF1 receptors associated with adipose tissue transplantation on fertility restoration in obese anovulatory mice.

The aim was to analyze the effect of adipose tissue transplantation on growth differentiation factor-9 (GDF-9), insulin growth factor 1 receptor (IGF1R), and leptin receptor (LEPR) protein expression in ovaries of obese anovulatory mice. Leptin-deficient female (ob/ob) and wild-type mice were divided into untreated ob/ob mice and gonadal white adipose tissue transplanted ob/ob mice, with evaluation after 7, 15, and 45 days and compared to control wild-type mice. The corporal weight and glycemia levels increased in the obese group concomitant with polymicrocyst formation and abundant estrone, mimicking anovulatory disease. In the treated group after 45 days, glycemia, weight, ovarian size, and number of follicles were decreased and corpora lutea were decreased. The analysis of GDF-9 revealed that, whereas control ovaries presented follicular localization, the obese ovary lacked this protein. On the other hand, obese ovaries showed elevated expression of IGF1R that was normalized after the transplantation. Finally, LEPR was reduced in obese ovaries, and adipose tissue transplantation was efficient in returning it to normal levels. In conclusion, the adipose tissue transplantation, especially after 45 days, seems to stimulate ovulation, supported by the fact that several proteins involved in ovulation returned to basal levels.

Treatment with a CRH-R1 antagonist prevents stress-induced suppression of the central neural drive to the reproductive axis in female macaques.

In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. When exposed to mild combined psychosocial plus metabolic stress (change in social environment plus reduced diet), female cynomolgus monkeys can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). Previously, we reported that monkeys that develop abnormal menstrual cycles following exposure to mild combined stress (MSR + SS) have increased plasma cortisol levels the day they move to a novel room and start a reduced diet compared with HSR monkeys. In this study, we examined whether there is a similar acute effect of mild combined stress on the reproductive axis specifically in the combined group of MSR + SS animals by measuring LH pulse frequency and whether treatment with a CRH-R1 antagonist can prevent a stress-induced suppression of LH pulse frequency presumably by inhibiting activity of the HPA axis. Animals that developed abnormal menstrual cycles in response to stress (MSR + SS monkeys) suppressed LH pulse frequency in response to stress exposure. Pretreatment with 10 mg/kg iv antalarmin prevented the stress-induced suppression of LH secretion in these animals without the stress-induced increase in cortisol secretion being blocked. We conclude that CRH, acting via nonneuroendocrine mechanisms to regulate neurotransmitter systems other than the HPA axis, plays a role in causing stress-induced reproductive impairment in stress-sensitive individuals.

Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist.

OBJECTIVE: To evaluate the protective effect of GnRH agonist for the prevention of ovarian reserve during treatment with paclitaxel and cisplatin. DESIGN: Experimental study. SETTINGS: University-based research laboratory. ANIMAL(S): Seventy female Wistar-Albino rats. INTERVENTION(S): Each group consisted of 10 rats. Group 1 served as controls. Groups without GnRH agonist (groups 2, 3, and 4) were administered paclitaxel and cisplatin, respectively; the remaining groups (groups 5, 6, and 7) were given the same regimens with GnRH agonist. The GnRH agonist (leuprolide acetate; 2.5 microg/d subcutaneously for 5 weeks) was started four weeks before chemotherapy to achieve anovulation. Paclitaxel (7.5 mg/kg) and cisplatin (5 mg/kg) were administered intraperitoneally on the 28th day as a single dose. MAIN OUTCOME MEASURE(S): One week after the chemotherapy, the animals were euthanized and primordial, primary, secondary, and tertiary follicle counts were evaluated. RESULT(S): Primordial, primary, and tertiary follicle counts in group 5 (paclitaxel plus GnRH agonist) and tertiary follicles in groups 2 and 3 had not decreased, but there was a significant decrease in other treatment groups compared with controls (P < 0.05). Binary comparison between all groups demonstrated that the primordial follicle count in group 5 was comparable to those of the controls. CONCLUSION(S): Paclitaxel plus GnRH agonist treatment may be an appropriate option for patients deserving further fertility in the preservation of primordial follicles.

Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility.

OBJECTIVE: To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility. DESIGN: A prospective cohort study. SETTING: The Nurses' Health Study II. PATIENT(S): Eighteen thousand five hundred fifty-five married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999. INTERVENTION(S): None, observational study. MAIN OUTCOME MEASURE(S): Incident reports of infertility caused by anovulation. RESULT(S): During 8 years of follow-up, 438 women reported infertility caused by ovulatory disorder. There was an inverse association between frequency of multivitamin use and ovulatory infertility. The multivariate-adjusted relative risk (95% confidence interval) of ovulatory infertility was 0.88 (0.60, 1.28) for women consuming two tablets per week or less, 0.69 (0.51, 0.95) for women consuming three to five tablets per week, and 0.59 (0.46, 0.75) for women consuming six or more tablets per week, when compared with women who did not use these supplements (P, trend <.001). Folic acid appeared to explain part of the association between multivitamin supplement use and risk of ovulatory infertility. CONCLUSION(S): Regular use of multivitamin supplements may decrease the risk of ovulatory infertility.

Continuous administration of low-dose GnRH in mares II. Pituitary and ovarian responses to uninterrupted treatment beginning near the autumnal equinox and continuing throughout the anovulatory season.

We tested the hypothesis that continuous subcutaneous treatment with low-dose GnRH, administered to mares from late September/early October through March, would prevent the development of seasonal anovulation. Quarter Horse mares (n=20) were stratified by age and body condition score and assigned randomly to either a saline control (n=9) or a GnRH (n=11) treatment group. Gonadotropin-releasing hormone was delivered continuously via osmotic minipumps, with sham pumps placed in control mares. Initial pumps were inserted on Day 3 following ovulation or during the follicular phase if the next anticipated ovulation did not occur by 9 October. Delivery rate of GnRH was 2.5 microg/h (60 microg/day) for the first 60 days, followed by 5.0 microg/h (120 microg/day) thereafter. Pumps were replaced every 30 days. Eighty and 100% of all mares had become anovulatory by 1 November and 1 December, respectively, and remained anovulatory through the end of February. Neither serum concentrations of LH throughout the study nor total releasable pools of LH in March differed between groups. Although control mares that exhibited ovulatory cycles after study onset had greater (P<0.05) mean concentrations of LH during the follicular phase and metestrus compared to GnRH-treated mares, neither size of ovulatory follicles nor interovulatory intervals differed between groups. Serum concentrations of FSH were not affected by treatment, but were lowest (P<0.05) from November through January. Continuous infusion of low-dose GnRH, beginning soon after autumnal equinox and continuing until just after vernal equinox, failed to prevent the occurrence of or to hasten transition from seasonal anovulation.

The impact of bariatric surgery on menstrual patterns.

BACKGROUND: Obesity and anovulation are common medical problems in the United States. Anovulation in obese patients primarily manifests with irregular, sporadic or absent menstrual bleeding. Weight loss of at least 5% has been shown to reverse obesity-related anovulation. The aim of this study was to assess the impact of bariatric surgery on infertility in morbidly obese women and to identify factors associated with return of normal menses following bariatric surgery. METHODS: A survey of patients was collected from the bariatric surgery data-base at the Hospital of the University of Pennsylvania. 410 women under the age of 40 were sent questionnaires. 195 patients completed the questionnaire, and 29 patients had incorrect addresses without a forwarding address, resulting in a 51.2% response rate. Patients who reported menstrual cycle lengths >35 days were considered abnormal. 92 of the 195 responders were considered anovulatory preoperatively, based on menstrual history. RESULTS: There was no significant difference in postoperative BMI, BMI decrease or age at surgery between the survey responders and non-responders. There was a significant difference between these 2 groups in time since surgery (P=.01). Both groups had a decrease in BMI of >18 kg/m(2). The mean menstrual cycle length preoperatively among those categorized as ovulatory and anovulatory was 27.3 and 127.5 days, respectively. Of the 98 patients who were anovulatory preoperatively, 70 patients (71.4%) regained normal menstrual cycles after surgery. Those patients who regained ovulation had greater weight loss than those who remained anovulatory (61.4 kg vs 49.9 kg, P=0.02). CONCLUSIONS: Anovulation resulting in abnormal menses is a common problem in morbidly obese premenopausal women. The menstrual cycle disorders may completely resolve after bariatric surgery. Thus, infertility due to anovulation among morbidly obese women could potentially be viewed as an additional indication for bariatric surgery.

Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone.

OBJECTIVE: To compare the effectiveness and efficiency of two low-dose step-up protocols for ovulation induction in women with anovulatory infertility (World Health Organization group II). DESIGN: Open-label, prospective, randomized, group-comparative, multicenter study. SETTING: Eighteen infertility centers in Europe and Canada. PATIENT(S): One hundred fifty-eight anovulatory or oligo-ovulatory infertile women. INTERVENTION(S): Patients were randomly assigned to one of two protocols for one cycle of follitropin beta (rFSH) using a pen device. The starting dosage was 50 IU/day for 7 days. In the absence of follicles > or =12 mm, the daily dosage was increased by either 25 or 50 IU per week. MAIN OUTCOME MEASURE(S): The percentage of all subjects treated who ovulated after one treatment cycle (efficacy) and the total rFSH dose to reach ovulation (efficiency). RESULT(S): The 25-IU group had a higher incidence of monofollicular growth (41.3% of 80 vs. 21.8% of 78 women) and ovulation (81.3% vs. 60.3%), a lower cumulative rFSH dose (887 IU vs. 984 IU), and fewer cancellations due to hyperresponse (>3 follicles > or =15 mm; 5.0% vs. 20.5%). Both protocols were well tolerated. CONCLUSION(S): Weekly increments of 25 IU in the daily dose were more effective and efficient than 50-IU increments.

Metformina en el tratamiento de la anovulación asociada a insulino-resistencia / Use of metformin on anovulation associated insulin-resistance

Se presentan 18 casos de pacientes infértiles anovulatorias en que se efectuó el diagnóstico de insulino resistencia y fueron tratadas con metformina. Once pacientes se embarazaron, 7 con metformina y 4 al asociar citrato de clomifeno. Seis pacientes tuvieron parto de término, 2 presentaron aborto de primer trimestre y 3 embarazos están en curso. De los 6 embarazos de término, 2 presentaron diabetes gestacional. Se revisa la literatura y se discute la conveniencia de mantener el tratamiento con metformina durante el embarazo para prevenir diabetes gestacional.

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation. 3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose-dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration. 4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose-dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared. 5. These results suggest that cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.

The effect of a special herbal tea on obesity and anovulation in androgen-sterilized rats.

A special herbal tea has been used to treat clomiphene-resistant anovulatory disease and obesity effectively, especially in polycystic ovary syndrome (PCOS) cases with hyperinsulinemia. The effect of the herbal tea on obesity and anovulation was investigated in androgen-sterilized rats (ASR). The ASR model was established by subcutaneous injection of 1.25 mg testosterone propionate to Sprague-Dawley female rats at the age of 9 days. Rats were sacrificed around 112 days of age. ASR manifested with PCO, anovulation, high food intake, elevated body weight, and obesity. Immunocytochemistry demonstrated that estrogen receptors (ER) were predominantly distributed in the cytoplasm of neuropeptide Y (NPY)-containing neurons in the preoptic area (POA), and the coexpression was also found in the nuclei and fibers of NPY-synthesizing neurons in the arcuate nucleus (ARC). Compared with that in normal control rats, NPY expression was increased, the numbers of ER in hypothalamic ARC-median eminence (ME) decreased, gonadotropin-releasing hormone (GnRH) levels in ME was decreased, serum estrogen (E2) and leptin were elevated, and follicular stimulating hormone (FSH) and luteinizing hormone (LH) levels were reduced significantly in ASR. Significantly negative correlations between NPY and ER or GnRH, and between leptin and FSH or LH were observed. A positive correlation existed between serum leptin and body weight. These metabolic-endocrine changes in ASR were normalized after feeding the herbal tea. Both obesity and hypogonadotropin were expressed in ASR. The abnormal ovarian hormone milieu (elevated E2 levels) may have enhanced NPY expression and resulted in less GnRH and gonadotropin secretion. The herbal tea reduced body weight and induced ovulation in ASR.

Anesthetic pregnanes counteract androgen-induced defeminization.

The capacity of various pregnanes for counteracting androgen-induced defeminization was evaluated in an attempt to define some cellular mechanisms involved in the defeminization process. 5-day-old female rats received 60 microgram testosterone propionate (TP) along with one of various pregnanes: progesterone, 5 beta-pregnandione, 5 beta, 3 alpha-pregnanolone, 5 beta, 3 beta-pregnanolone, 5 alpha-pregnandione, 5 alpha, 3 beta-pregnanolone, 5 alpha, 3 alpha-pregnanolone or chlormadinone acetate. Protection against defeminization was defined as a significantly smaller proportion of anovulatory animals in a group compared to the control TP group. Data were analyzed at 60, 90 and 120 days of age. The anesthetic potency of the pregnanes was evaluated in 5-day-old male rats through the analysis of EEG and EMG records. Anesthetic pregnanes - progesterone, 5 beta-pregnandione and 5 beta, 3 alpha-pregnanolone - counteracted defeminization while nonanesthetic pregnanes - 5 alpha-pregnanes, chlormadinone acetate and 5 beta, 3 beta-pregnanolone - did not. The results show a clear relation between anesthetic capacity and protection against defeminization.

[Preventive action of catecholamine and serotonin synthesis inhibitors and of adrenergic blockaders on the occurrence of the anovular syndrome in neonatally androgenized rats. I]. / Preventivnoe deistvie ingibitorov sinteza katekholaminov, serotonina i adrenblokatorov na vozniknovenie anovuliatornogo sindroma u neonatal'no androgenizirovannykh krys. Soobshchenie I.

Administration of catecholamine synthesis inhibitors (alpha-methl-p-tyrosine) or serotonin (parachlorphenylalanine) simultaneously with testosterone propionate prevented the anovular sterility in the majority of the neonatally androgenized rats. Preventive action of adrenoblockers (droperidol and propranolol) on the effects of early androgenization were weak. The data obtained pointed to the participation of catecholamines and serotonin in the realization of the masculinizing action of androgen on the neuroendocrine centres of the gonadotropin hormones secretion control.