[New possibilities of treatment of sterility caused by functional anovulation].
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Clinical effects of clomiphene in anovulation.
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[Treatment of anovulation with HMG].
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[Treatment of anovulation by Clomid].
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[Ovulation and modern anovulators].
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Contraceptives, Oral↗
Management of anovulatory infertility.
Chronic anovulation is probably the major cause of human infertility and is essentially associated with four distinct endocrine conditions; hyperprolactinemic anovulation, hypogonadotrophic anovulation, normo-gonadotrophic anovulation and hypergonadotrophic anovulation. Hyperprolactinaemia and microprolactinoma are frequent findings in young women and excessive prolactin secretion impairs ovarian function causing anovulatory subfertility. Dopaminergic treatment restores ovarian function and shrinks prolacinoma. In these patients restoration of fertility with prolactin lowering drugs does not increase the incidence of multiple pregnancies or early pregnancy loss. In the vast majority of hyperprolactinemic women pregnancy is safe and could be beneficial. Cabergoline is the most effective and tolerated of the antiprolactinemic drugs. Hypogonadotrophic anovulation is frequently associated with acute or chronic emotional stress and in this case the patient should be counselled. Explanation and reassurance are the first important management steps. The use of pulsatile gonadotrophin-releasing hormone is the best strategy to induce fertility. Patients with normogonadotrophic anovulation are likely to have polycystic ovary. The most cost effective profertility treatment is the administration of an anti-oestrogen such as clomiphene or tamoxifen. The second choice therapy for patients with normogonadotrophic anovulation is ovarian stimulation with human gonadotrophin preparations. Low dose modifications give pregnancy rates lower than that with the traditional high-dose step-up protocol and intensive monitoring is required, but multiple pregnancies are less frequent. No treatment is available to enable women with hypergonadotrophic anovulation to conceive. Fertility in these patients can be promoted only by an egg donation programme.
Anovulation↗
Polycystic ovary syndrome.
The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non-insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of androgens, particularly T. A fundamental mechanism of ovarian hyperandrogenism in PCOS is LH hypersecretion. Whether the central nervous system is a possible locus for initiating LH hypersecretion remains unclear, because exaggerated LH secretion is temporarily reversed by induced ovulatory cycles or physiologic luteal concentrations of progesterone. On the other hand, desynchronization of pulsatile LH secretion from sleep in girls with PCOS and an exaggerated (e.g., masculinized) early LH response to GnRHa testing in women with hyperandrogenic anovulation and congenital adrenal virilizing disorders suggest that events occurring before puberty, perhaps during fetal life, may irreversibly alter neuroendocrine function. Hyperinsulinemia from insulin resistance is an important regulatory mechanism governing ovarian hyperandrogenism. Hyperinsulinemia in hyperandrogenic anovulatory women potentiates ovarian hyperandrogenism by enhancing LH secretion; potentiating 17-hydroxylase and, to a lesser extent, 17,20-lyase activity; and suppressing SHBG capacity. It is a key component of hyperandrogenic anovulation caused by a type of insulin resistance that in independent and additive to that of obesity alone. Although the mechanisms governing insulin action on ovarian steroidogenesis are unknown, abnormalities of intracellular insulin signaling or cytochrome P450c 17[alpha] activity may render the 17-hydroxylase/17,20-lyase enzyme complex more sensitive to insulin. Hyperinsulinemia in hyperandrogenic anovulatory women is accompanied by upper-body obesity characterized by an increased amount of abdominal fat. Upper-body obesity is an important independent risk factor for CVD and diabetes. Although genetic and environmental factors affect fat distribution, sex steroids, particularly androgens, regulate lipid metabolism, suggesting yet another link between the hormonal and metabolic abnormalities of hyperandrogenic anovulation. A careful history and physical examination guide the extent of diagnostic testing. Slowly progressive hirsutism with anovulation of peripubertal onset usually reflects hyperandrogenic anovulation. This type of clinical presentation requires an evaluation to rule out other endocrinopathies (e.g., virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome). Virilization or severe rapidly progressive hirsutism requires immediate investigation to rule out a possible virilizing tumor. The ultimate goals of therapy for hyperandrogenic anovulatory women are to normalize the endometrium, antagonize androgen action at target tissues, reduce insulin resistance, and correct anovulation, if necessary.
Female↗
The effect of chronic and acyclic elevation of circulating androstenedione or estrone concentrations on ovarian function in the rhesus monkey.
The concept that chronically elevated blood androstenedione concentrations increase the incidence of anovulation in the primate and that acyclic elevated basal blood androgen and/or estrogen concentrations cause abnormal gonadotropin secretion was studied. Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing filled with androstenedione or estrone and compared with controls. Androstenedione implants increased the serum androstenedione concentrations from 1.6 +/- 0.1 (SE) ng/ml to 6.30 +/- 0.27 ng/ml. By peripheral conversion the testosterone concentration increased from control values of 279 +/- 10 (SE) pg/ml to 1280 +/- 41 pg/ml. The testosterone concentration in the estrone-treated monkeys was 247 +/- 9.7 pg/ml. The estrone concentrations were: controls, 63.2 +/- 3.1 (SE) pg/ml; androstenedione-treated monkeys, 63.2 +/- 3.1 pg/ml; and estrone-treated animals, 150 +/- 5.3 pg/ml. The corresponding estradiol concentrations were: control animals, 35.1 +/- 2.1 (SE) pg/ml; androstenedione animals, 30.9 +/- 1.8 pg/ml; and estrone-treated monkeys, 65.7 +/- 3.9 pg/ml. There was no difference in the morning serum cortisol concentrations between any of the three groups or between ovulatory or anovulatory months. The chronic elevation of either androstenedione or estrone caused an increased incidence of anovulation compared with the controls. Increased estrogen concentrations caused increased anovulation during both summer and winter months; however, increased androgen concentrations caused increased anovulation only during the summer months. However, LH concentrations were unaffected in either group but were lower during anovulation months in all three groups. An LH or FSH surge followed an estradiol bolus in three of four control animals and four of six androstenedione-treated but none of the estrone-treated monkeys. Histological examination of ovarian biopsies demonstrated thickening of the tunica albuginea ovarii in androgen-treated ovaries and an apparent increased number of atretic follicles. Corpora lutea were absent in the ovaries of the estrogen-treated monkeys, but otherwise these ovaries were similar to those of controls. It is concluded that chronic acyclic elevation of blood androstenedione (and resultant testosterone) increases seasonal anovulation in the rhesus monkey. Increased blood estrone (and resultant estradiol) leads to almost complete anovulation throughout the year and renders the central nervous system-pituitary axis insensitive to positive feedback effect of estradiol. Neither treatment caused an increase in basal LH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenal Cortex↗
Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.
BACKGROUND: Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection was the first established treatment for anovulatory PCOS patients but was largely abandoned of the risk of post-surgical adhesion formation. It was replaced by medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Although effective, it is an expensive, stressful and time consuming form of treatment requiring intensive monitoring. A new surgical therapy, laparoscopic ovarian "drilling", may avoid or reduce the need, or facilitate the use, of gonadotrophins for inducing ovulation. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. It has been claimed in many uncontrolled observational studies that it is followed, at least temporarily, by a high rate of spontaneous postoperative ovulation and conception, or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness of laparoscopic ovarian drilling for ovulation induction in subfertile women with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS). SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of randomised controlled trials (RCTS). A computerised MEDLINE search was used to identify non randomised controlled trials. SELECTION CRITERIA: Trials were eligible for inclusion if treatment consisted of laparoscopic ovarian drilling in order to induce ovulation in subfertile women with PCOS and compared with a concurrent control group. DATA COLLECTION AND ANALYSIS: Fourteen trials were identified; eight were included in the review of which seven were randomised. All trials were assessed for quality criteria. The main studied outcomes were ovulation and pregnancy rates. Miscarriage rate, multiple pregnancy rate, and incidence of overstimulation and ovarian hyperstimulation syndrome rate were secondary outcomes. MAIN RESULTS: With the exception of multiple pregnancy rates no differences were demonstrated for any of the interventions studied but the numbers of patients who have been randomised to controlled studies at this time is insufficient to conclude that laparoscopic ovarian drilling is more effective than gonadotrophin therapy for other outcomes. REVIEWER'S CONCLUSIONS: The value of laparoscopic ovarian drilling as a primary treatment for subfertile patients with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS) is undetermined. There is insufficient evidence to determine a difference in ovulation or pregnancy rates when compared to gonadotrophin therapy as a secondary treatment for clomiphene resistant women. Multiple pregnancy rates are reduced in those women who conceive following laparoscopic drilling. None of the studied modalities of drilling technique had any obvious advantages.
Anovulation↗
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.
Animals↗
Predictors for treatment failure after laparoscopic electrocautery of the ovaries in women with clomiphene citrate resistant polycystic ovary syndrome.
BACKGROUND: Laparoscopic electrocautery has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). In order to make an informed treatment decision it would be helpful if we could identify women with PCOS with a high probability of treatment failure following electrocautery of the ovaries. METHODS: Eighty-three women with CC-resistant PCOS were allocated to receive laparoscopic electrocautery followed by CC when anovulation persisted as part of a randomized controlled trial. Multivariable logistic regression analyses using clinical, ultrasonographic and endocrinological parameters were performed to predict (i) failure to ovulate within 8 weeks after electrocautery, and (ii) failure to reach an ongoing pregnancy after electrocautery with or without CC. RESULTS: Of the 83 women, 56 (67%) ovulated within 8 weeks after electrocautery. The model for predicting anovulation after electrocautery included LH/FSH rate, year of menarche and glucose level. Women who were younger at menarche, had a lower LH/FSH ratio and a lower glucose level were more likely to have persistent anovulation. The area under the curve was 0.74. After electrocautery and CC, 41 women reached an ongoing pregnancy. No prognostic parameters could be identified to predict failure to reach an ongoing pregnancy after electrocautery followed by CC. CONCLUSIONS: Persistence of anovulation after electrocautery could be predicted and women with a high risk of persisting anovulation could be distinguished. We were, however, not able to predict treatment failure after electrocautery followed by CC.
Adult↗
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.
Adult↗
[Comparative morphofunctional characteristics of the ovaries in women of reproduction age in the norm and with chronic anovulatory infertility].
This work was aimed at the study of ovarian histophysiology in patients with chronic anovulation. The biopsy specimens obtained by endoscopic laparoscopy from the ovaries of women of reproductive age with anovulation or normal cycle (control) were examined. It was found that in the ovaries of anovulation patients the thickness of both tunica albuginea and follicular theca externa was increased. The number of primordial follicles was not different in groups studied, while the number of antral follicles was decreased in anovulation group. No differences in 3 beta-hydroxysteroiddehydrogenase and NADH-dehydrogenase activities in the cells of theca interna and cyst walls were found in both groups, while NADPH-dehydrogenase and NO-synthase activities in these structures were reduced in anovulation. Reduction of estradiol concentration and increase of testosterone concentration were noted in blood of women with anovulatory infertility. The data obtained can be used for the analysis of etiology and pathogenesis of anovulatory infertility and for development of the methods of its treatment.
Adolescent↗
Prevalence of hyperprolactinemia in anovulatory women.
To determine the prevalence of hyperprolactinemia in an ovulatory patients presenting to a general gynecology clinic, a 1-year prospective study (1978) was instituted. A total of 119 patients with at least 3 months of anovulation were screened with serum prolactin determinations. Those patients demonstrating hyperprolactinemia were further evaluated with a serum TSH level and hypocycloidal polytomography of the pituitary sella. In patients with anovulation with or without galactorrhea, a hyperprolactinemia prevalence rate of 15% was established. Anovulatory patients with galactorrhea had a hyperprolactinemia prevalence rate of 43%. This was compared to the 9% prevalence of hyperprolactinemia in patients with nongalactorrheic anovulation (P less than .001). Twenty-two percent of the patients with nongalactorrheic anovulation (2 of 9) were found to have a prolactin-secreting pituitary adenoma. In patients with hyperprolactinemia, galactorrhea, and anovulation, 67% (6 of 9) of patients had a prolactin-secreting pituitary adenoma. The authors therefore conclude that the 15% prevalence rate of hyperprolactinemia in all anovulatory women is sufficiently high to warrant continued screening of serum prolactin determinations in all anovulatory women.
Adenoma↗
The ratio of androstenedione:11 beta-hydroxyandrostenedione is an important marker of adrenal androgen excess in women.
OBJECTIVE: To determine if the ratio of serum androstenedione (A):11 beta-hydroxyandrostenedione (OHA) would be helpful in differentiating adrenal from ovarian hyperandrogenism. DESIGN/SETTING: Prospective study of outpatients being evaluated for hyperandrogenism. PATIENTS/PARTICIPANTS: Normal women (n = 27), those with hyperandrogenic chronic anovulation (n = 25), and 7 with adult onset of congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. INTERVENTIONS: Fasting serum between 8:00 A.M. and 9:00 A.M. Patients with hyperandrogenic chronic anovulation and CAH received dexamethasone (DEX) 2 mg for 7 days. MAIN OUTCOME MEASURES: Serum testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), A, and 11 beta-OHA by radioimmunoassay. RESULTS: Serum 11 beta-OHA and DHEAS were elevated in 52% and 40% of patients with hyperandrogenic chronic anovulation and in 7 of 7 and 1 of 7 patients with CAH. The ratio of A:11 beta-OHA was significantly higher (P less than 0.05) in hyperandrogenic chronic anovulation and significantly lower (P less than 0.05) in CAH compared with controls. Serum A:11 beta-OHA correlated with T (r = 0.58, P less than 0.05). The ratios of A:11 beta-OHA were similar and significantly lower in CAH and hyperandrogenic chronic anovulation patients who were DEX sensitive compared with those who were not DEX sensitive. The ratio correlated with the percentage suppression of T, unbound T, and A after DEX (P less than 0.01). There were no differences with measurements of DHEAS and 11 beta-OHA. Using the mean ratio of controls (1.3) as a cutoff value, the sensitivity of the A:11 beta-OHA in detecting adrenal hyperandrogenism, as assessed by DEX sensitivity, was 100%, the specificity was 84%, and the predictive value was 67%. CONCLUSIONS: The ratio of A:11 beta-OHA appears to be an excellent marker for identifying patients with adrenal hyperandrogenism and CAH.
Adolescent↗
[Polycystic ovarian disease: clinical and biochemical expression].
UNLABELLED: The policystic ovary (PO) results from a systemic hormonal dysfunction, characterized by hyperandrogenemia, insulin resistance and anovulation. OBJECTIVE: Assessment was made of clinical and biochemical features of patients with PO. MATERIAL AND METHODS: A retrospective analysis of 211 clinical of charts of patients with ultrasonographic diagnosis of PO seen at the Hospital Juárez de México from 1996 to 2000 was performed. Evaluation was made of body mass index (BMI), waist hip index (WHI), Ferriman index, acanthosis nigricans, lipid and hormonal profile. RESULTS: Of patients studied (n = 211) 64% had infertility and abnormal menses associated to PO, while the rest was normal. Both groups (PO and normal), were similar in age and distribution as well as family back grown for diabetes mellitus, hypertensive disease and obesity. The clinical manifestations observed on patients with PO were infertility 79.16%, anovulation 68.42%, hirsutism 66.9% obesity (66.9%). Biochemical findings in PO patients vs normal patients were: hyperandrogenism (86.73% vs 71.4%), insulin resistance (60.46% vs 37.5%), dislipidemic (56.41% vs 31.5%), LH/FSH ratio > 2 (19.51% vs 10.51%). Regarding sensitivity and specificity for clinical and biochemical findings ranged from 0.64 at 0.90, minimum value had infertility and maximum anovulation; specificity (interval 0.31 to the 0.71) minor corresponded to hyperprolactinemia and higher to infertility. The estimated risk factor (OR) for the population studied exhibited anovulation (OR, 7; 95% IC, 1.79-32.92); infertility (OR, 4.51; 95% IC, 2.03-10.13); insulin resistance (OR, 3; 95% IC, 0.82-8.16); hyperandrogenism (OR, 2.61; 95% IC, 1.02-6.69); and obesity (OR, 2.16; 95% IC, 1.17-4). We concluded that population with PO has a higher risk of infertility, anovulation, obesity, hyperandrogenism, dyslipidemia, insulin resistance and abnormal menses.
Adolescent↗
Ovulatory disturbances. Causative factors among Japanese student nurses in a dormitory.
The incidence of ovulatory disturbances in student nurses living in a restricted circumstance was evaluated by observing a basal body temperature (BBT) chart recorded for three to nine months by all of the student nurses in our medical college. The students were 18-21 years of age and were all living in a school dormitory. One hundred of the 154 students (64.9%) were anovulators during the school term. However, 40 of the anovulators showed ovulatory cycles with biphasic BBT patterns during their spring and/or summer holidays. The subjects' living conditions were investigated by questionnaire. Age of menarche, sport activity, self-perceived physical and mental work load, and native region did not appear to be related to their ovulatory disturbances. Weight-height-derived indices indicated that the anovulators had a tendency to corpulence as compared to the regular ovulators. Serum luteinizing hormone, follicle stimulating hormone, and prolactin levels of the anovulators were not significantly different from the regular ovulators.
Adolescent↗
Effect of leptin administration on ovulation in food-restricted rhesus monkeys.
A chronic negative energy balance due to low nutritional intake or increased energy expenditure alters several neuroendocrine axes. The reproductive and thyroid axes are inhibited while the adrenal axis is stimulated. In primates, anovulation resulting from a chronic negative energy balance is a condition often referred to as nutritional amenorrhea. The objective of the current study was to determine if hypoleptinemia induced by dietary restriction is responsible for these neuroendocrine changes, particularly anovulation. Five rhesus monkeys had their dietary intake gradually reduced to inhibit ovulation. Dietary restriction inhibited follicle-stimulating hormone (FSH) and triiodothyronine (T(3)) secretion and stimulated cortisol release. Recombinant human leptin (rhleptin) administered by continuous infusion into the lateral ventricle for 16 weeks inhibited cortisol secretion but failed to stimulate FSH, T(3) or ovulation. An immune response to rhleptin was noted after 3 weeks of leptin administration. Realimentation resulted in weight gain and reversed all endocrine responses to dietary restriction, including ovulation. These results do not support a role for reduced leptin secretion in anovulation induced by dietary restriction. The inability of rhleptin to reverse anovulation induced by a negative energy balance in monkeys is in contrast to its stimulatory effect on ovulation in women with functional hypothalamic amenorrhea. Different outcomes may be attributed to the degree of negative energy balance, the immune response generated by interspecies leptin administration, and/or other experimental variables such as dose or route of administration. Attributing opposing outcomes to species differences is unwarranted until these variables can be further examined.
Adaptation, Physiological↗