Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Ge...

Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications

BACKGROUND Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (i) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (ii) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny. The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition. METHODS A review of published literature was performed to address (i) androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, (ii) associations of androgen concentrations with adverse pregnancy outcomes, (iii) the role of androgens in the physiology of cervical remodelling and finally (iv) the role of androgens in the physiology of myometrial function including any impact on contractility. RESULTS Some, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens in myometrial relaxation via non-genomic, AR-independent pathways critical for the pregnancy reaching term. Understanding of the molecular events leading to myometrial relaxation is an important step towards development of novel targeted tocolytic drugs. CONCLUSIONS The increase in androgen levels throughout gestation is likely to be important for establishment and maintenance of pregnancy and initiation of parturition. Further investigation of the underlying mechanisms of androgen action on cervical remodelling and myometrial contractility is needed. The insights gained may facilitate the development of new therapeutic approaches to manage pregnancy complications such as preterm birth.

/pdf/androgens-in-pregnancy-roles-in-parturition-k2f9zz9v92.pdf

Androgens in pregnancy: roles in parturition

Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy affecting women of reproductive age, manifested with a variety of clinical signs, none of which is pathognomonic. The association of insulin resistance and reproductive abnormalities with clinical hyperandrogenism in a woman was first demonstrated by Achard and Thiers in the "diabetes of bearded woman." The link of PCOS with insulin resistance was subsequently established by clinical studies characterizing the profound insulin resistance in obese and lean PCOS patients. Insulin resistance, hyperinsulinemia, and beta-cell dysfunction are very common in PCOS, but are not required for the diagnosis. The numerous in vivo and in vitro data supporting the central role of insulin resistance in the pathogenesis of PCOS found a broad clinical application in the management of the syndrome, where the regulation of cycle abnormalities and the facilitation of pregnancy in obese PCOS patients was assisted by co-administration of agents such as the well-known insulin sensitizers. The documentation of the presence of insulin resistance contributed substantially to unravel several metabolic components present in the syndrome. Today our knowledge about PCOS appears to have broader health implications and to have profoundly altered our view of the gravity of this condition.

Insulin resistance in PCOS

Vaginoscopic approach to outpatient hysteroscopy: a systematic review of the effect on pain

Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in da...

https://www.tandfonline.com/doi/pdf/10.1080/19490976.2018.1441664

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Detection of benign intracavitary lesions in postmenopausal women with abnormal uterine bleeding: a prospective comparative study on outpatient hysteroscopy and blind biopsy

https://www.fertstert.org/article/S0015-0282(06)00683-2/pdf

Failure of the homeostatic model assessment calculation score for detecting metabolic deterioration in young patients with polycystic ovary syndrome

The incidence of hyperandrogenism during pregnancy is low, although the incidence of some of the ovarian diseases that can cause it is higher. Hyperreactio luteinalis is a rare benign condition that may mimic ovarian and trophoblastic malignancies. A 23-year-old woman at 20 weeks' gestational age presenting with severe hirsutism and ovarian masses was treated conservatively and subsequently gave birth to a healthy female neonate. Final diagnosis was hyperreactio luteinalis. Conservative management with close monitoring of patients with hyperreactio luteinalis represents the best approach in such rare cases. Counseling should be provided to reassure the patient as to the transient effects of hyperandrogenism on the mother and the fetus.

Hirsutism and hyperandrogenism associated with hyperreactio luteinalis in a singleton pregnancy: a case report.

Although there is a widespread on-going debate throughout the scientific community with regard to the pathogenesis of polycystic ovary syndrome, the association between this frequently observed endocrine disorder and insulin resistance has been universally acknowledged. Numerous tests have been proposed for use in assessing reduced sensitivity to insulin in women with polycystic ovary syndrome. The gold standard is represented by the euglycemic hyperinsulinemic clamp, although not yet available for application in routine clinical practice in view of its complexity and high cost. Measurement of oral glucose load and the use of several fasting tests feature a good degree of reliability and can be easily repeated. It remains to be ascertained, however, which therapeutic procedures, if any, are best suited for use in women affected by hyperinsulemia. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After reading this article, the reader should be able to outline metabolic consequences of polycystic ovarian syndrome (PCOS), conclude that testing insulin resistance is an important step in the care of women with PCOS, and recall the indications and limits of testing strategies for insulin resistance.

Diagnosis of metabolic disorders in women with polycystic ovary syndrome.

Surgical management of deep infiltrating endometriosis

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