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Query: UMLS:C0003128 (anovulation)
 1,718 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperandrogenic anovulation is characterized by polycystic appearance of the ovaries, elevated free serum testosterone with decreased concentrations of serum sex hormone binding globulin, an increased ratio of luteinizing hormone to follicle stimulating hormone and varying degrees of insulin resistance. We hypothesize that this is the result of variably increased 'ovarian androgenic insulin responsiveness' acting in combination with body mass. Women who develop hyperandrogenism and anovulation when lean (having normal serum insulin concentrations) represent the more severely affected individuals, whereas those who can resume ovulation by losing weight (and lowering their elevated serum insulin) represent a milder form. The tendency of these women to develop ovarian hyperstimulation syndrome despite hypophyseal desensitization suggests a primary ovarian defect which is apparently more pronounced in lean subjects. The unique ability of surgical damage to the ovary to induce ovulation, raises the possibility that inflammatory-like tissue remodelling has a major role in rescuing follicles from androgen-induced atresia. Approaches that may facilitate the study of this possible mechanism may include examination of in-vitro perfused, post-surgery mammalian ovaries and the elucidation of signal transduction mechanism(s) of insulin in the ovary, with special reference to cells emanating from affected women.
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PMID:Hyperandrogenic anovulation (the polycystic ovary syndrome)--back to the ovary? 974 12

Although central and peripheral factors have been implicated in the neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to establish a primary causal role for any one factor. Because increased GnRH pulse frequency is at least a contributor to the secretion of excess LH and insufficient FSH that are the proximate cause of chronic anovulation in PCOS, strategies to slow the GnRH pulse generator are likely to promote ovulation in women with PCOS. Several pharmacologic agents, such as dopamine agonists and antagonists, have been tried, but the lack of consistent effects in women with PCOS limits their clinical utility. Current treatment strategies include the use of the combined oral contraceptive pills, antiandrogens or androgen receptor blockers, and insulin sensitizers. Oral contraceptive preparations are effective in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens provide symptomatic relief from androgen-induced acne and hirsutism and have been reported to restore ovulation in women with PCOS. Whether this effect is mediated peripherally or centrally remains to be clarified. The most recent class of pharmacologic agents to gain popularity are the "insulin modifiers." With increasing evidence that insulin resistance constitutes a key metabolic element, it seems logical that improving insulin sensitivity and glucose disposal might wholly, or partially, reverse certain features of PCOS, including anovulation. To date, insulin modifiers have proved most promising in improving the clinical features and promoting fertility, but whether this effect is centrally mediated is yet to be elucidated.
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PMID:Neuromodulation in polycystic ovary syndrome. 1129 3

Polycystic ovary syndrome (PCOS) is the most common cause of female infertility affecting 6-8% of women worldwide. PCOS is characterized by two of the following three criteria: clinical or biochemical hyperandrogenism, oligo- or amenorrhea, and polycystic ovaries (PCO). In addition, women with PCOS are often obese and insulin resistant, and are at risk for type 2 diabetes and cardiovascular disease. The etiology of PCOS remains unknown. Therefore, several animal models for PCOS have been generated to gain insight into the etiology and development of the PCOS-associated phenotypes. Androgens are considered the main culprit of PCOS, and therefore, androgenization of animals is the most frequently used approach to induce symptoms that resemble PCOS. Prenatal or prepubertal androgen treatment results in many characteristics of human PCOS, including anovulation, cyst-like follicles, elevated luteinizing hormone (LH) levels, increased adiposity, and insulin insensitivity. However, PCOS has a heterogeneous presentation, and therefore it is difficult to generate a model that exactly reproduces the reproductive and metabolic phenotypes observed in women with PCOS. In this review, we discuss several mouse models for PCOS, and compare the reproductive and/or metabolic phenotypes observed in several androgen-induced models as well as in several genetic models.
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PMID:Mouse models to study polycystic ovary syndrome: a possible link between metabolism and ovarian function? 2460 53

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9-18% of women in reproductive age that causes hyperandrogenism and infertility due to dysfunctional follicular maturation and anovulation. The etiology of PCOS is still poorly known, and information from experimental animal models may help improve current understanding of the mechanisms of PCOS initiation and development. Therefore, we conducted a systematic review of currently available methods for simulation of PCOS in experimental models, focusing on two main endocrine traits: ovarian morphology changes and circulating levels of sex hormones and gonadotropins.We searched the MEDLINE database for articles in English or Spanish published until October 2016. Of 933 studies identified, 39 were included in the systematic review. One study compared interventions with androgens versus estrogens, 18 used androgen-induced stimulation, 9 used estrogens or drugs with estrogen action, including endocrine disruptors, to induce PCOS-like models, and 12 used miscellaneous interventions. Broad differences were found among the studies concerning hormonal interventions, animal species, and developmental stage at the time of the experiments, and most models resulted in ovarian morphology changes, mainly increases in the number of cystic and antral follicles and decreases in the corpus luteum. Hyperandrogenism was produced by using androgens and other drugs as the stimulatory agent. However, studies using drugs with estrogenic effect did not observe changes in circulating androgens.In conclusion, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype, in rhesus macaque and rat models respectively. In rats, postnatal exposure to androgens results in reprogramming of the hypothalamic-pituitary-ovarian-axis. Thus, comparisons between different intervention models may be useful to define the timing of reproductive PCOS phenotypes in experimental animal models.
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PMID:Animal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: a systematic review. 2818 10

Hyperandrogenism is one of the most common causes for anovulation in women and increases the risk for metabolic disorder in PCOS patients. Autophagy plays an important role in dysfunction of endocrine and anovulation. However, the relationship between hyperandrogenism and autophagy in human granulosa cells of PCOS patients remains unclear. By collecting granulosa cells from PCOS patients and non-PCOS patients, we found that the abundance of autophagy-related genes ATG5, ATG7, BECN1 mRNA and the ratio of autophagy marker protein light chain 3B II/I (LC3 II/I) were significantly increased whereas the abundance of the autophagy substrate SQSTM1/p62 was decreased in ovarian granulosa cells from PCOS patients. Furthermore, we demonstrated that BECN1 mRNA abundance in human granulosa cells positively correlated with the basal level of serum total testosterone and androgen up-regulated the abundance of BECN1 mRNA and the ratio of LC3II/LC3I in a dose-dependent manner in cultured granulosa cells. These observations indicated that androgen-induced activation of autophagy may play an important role in the development of PCOS and to explore the autophagy mechanisms involved in PCOS yield new insight into the pathophysiology and therapy of the disorder.
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PMID:The role of androgen in autophagy of granulosa cells from PCOS. 3105 90