目的： PCOS 是女性最常见的内分泌疾病, 其症状与并发症严重危害了女性的身心健康。本研究通过收集整体近10 年关于PCOS 的中医临床研究类文献，对本病的证型、治法，尤其是用药处方进行统计、归纳、分析’从而总结出该病的病因病机分布及治疗规律，为PCOS 下一步的临床治疗及用药提供思路和依据。方法：以“多囊卵巢综合征”、“PCOS”、“多囊卵巢”、“不孕症”、“闭经”“中医” 、“中医治疗”、“中医药”等为关键词’搜索2006 年1 月至2016 年12 月刊登在中文学术期刊上有关多囊卵巢综合征中医临床研究类文献，通过建立数据库，对其中医证型及使用方药进行统计分析’归纳总结出多囊卵巢综合征的主要病因病机及治疗用药规律。结果：经过筛选最终得到120 篇文献，共记录病例5670 例，明确治法4616 例，明确证型3778 例。肾虚证型2598 例（ 68. 8% ）；痰湿阻滞型613 例(16. 2%)占84.8% 侨肾3172 例（ 68. 7% ）补肾法中辅以活血化痰之法者也497 例（ 78. 7% ）。药物使用频共中’补虚药（ 43. 7% ）、活血化痕药（ 16.1% ），占59.8% 。归纳的两种疗效评判标准中，总有效率分别为87.9% 、88.9% 。结论： 1. 肾、肝、脾功能失调为PCOS 的发病之源。2. 肾虚、痰湿、血痕是PCOS 的基本病机。3. 补肾健脾，活血化痰是治疗PCOS 的根本大法。4. 补虚药、活血化寐药为治疗PCOS 的主导药物类别。5 中医药治疗PCOS 有副作用小基本黛痛苦璧幢调筒H p O 轴的功能。6. 不同年龄段治疗目的不同导致疗效评判标准尚不统一。关键词：多囊卵巢综合征，中医，用药规律，文献研究

Class of 2008 Abstract / Objectives: To assess the effect of metformin usage and lifestyle modifications in women with polycystic ovary syndrome (PCOS) in achieving conception and live birth. Methods: A retrospective chart review of patients at a southwest reproductive health center was performed. Patients given a diagnosis of PCOS, treated with metformin alone, with at least 12 weeks of outcome data were enrolled. Diagnostic, reproductive history, and baseline endocrine and metabolic data were collected. All available metformin use, menstrual cyclycity, ovulation, pregnancy, pregnancy outcome, and alternative treatment data were captured. Results: A total of 1250 charts were reviewed and 103 patients were enrolled. Pre-treatment, a significant relationship between BMI and HDL, triglycerides/HDL, and fasting glucose (P <0.001, 0.018, 0.016) was noted with leaner patients having better metabolic profiles. The pregnancy, miscarriage, and live birth rates with metformin treatment were 55.3 %, 18.2 %, and 35.0 % respectively. Patients (40/103) that did not conceive with metformin attempted alternative fertility treatment; 55% became pregnant and 30% had a live birth. One third of all patients experienced minor adverse events, primarily gastrointestinal in nature. Logistic regression analyses comparing responders to nonresponders did not identify any baseline patient characteristics useful as significant predictors of success with metformin treatment. Conclusions: For the population under study, metformin use and lifestyle modifications resulted in conception and live birth for as many as 35 % of patients. Contrary to recent publications, it appears that this method of fertility treatment remains a viable option to treat infertility in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder affecting reproductive-aged women. It is diagnosed using a combination of menstrual irregularity, clinical and/or biochemical hyperandrogenism and polycystic ovary morphology upon ultrasound. Hyperandrogenism in females may clinically manifest as hirsutism, acne, alopecia, or other masculinization of features. Assessing total/free testosterone, dehydroepiandrosterone sulfate, and 17-hydroxyprogesterone provides biochemical evidence of hyperandrogenism. OBJECTIVE: To determine self-reported clinical signs of androgen excess using data from the Ovulation and Menstruation Health (OM) Study, a diverse, multi-ethnic cohort study being conducted at Boston University School of Medicine. METHODS: Data was collected from participants enrolled in the Ovulation and Menstruation Health Study pilot cohort. This epidemiologic survey captured demographics, menstrual cycle patterns, PCOS histories, reproductive histories and manifestations of androgen excess in a diverse patient population. Participants were women ages 18-45 who had the capacity to ovulate/menstruate at the time of the study, had no history of chemotherapy, radiation, or surgical menopause, and were not pregnant at the time of the study. To assess androgen excess, participants were asked to self-report hair growth in nine body areas, acne on the face and back and hair loss on the scalp. The nine body areas were scored using the modified Ferriman-Gallwey (mFG) scoring system. Reference images created by a medical illustrator were used for hirsutism and alopecia grading while clear descriptions were provided for grading acne severity. Clinical hirsutism was defined as total mFG score of ≥ 8, or ethnic specific cutoff for East Asian (≥ 2) and Southeast Asian (≥ 3) women. Alopecia was defined as scalp hair loss ≥ 2. For participants that consented to medical record validation total, free and bioavailable testosterone lab levels were assessed for biochemical hyperandrogenism evaluation. RESULTS: Beginning August 9, the day the study opened to the public, 249 participants completed the pilot survey questionnaire. These participants were 66.8% white (n=165), 6.5% Hispanic or Spanish origin (n=16), 10.5% Black or African-American (n=26), 1.6% East Asian (n=4), 2.0% Southeast Asian (n=5), 2.4% South Asian (n=6), and 10.9% were of mixed ethnic backgrounds (n=27). 22.5% (55/245) of these women had clinical hirsutism by total mFG score. Mean total mFG scores were highest in women who were South Asian at 13.8±9.1 (n=6) and Hispanic at 8.6±8.7 (n=16). Moderate-severe acne was reported in 23.6% (58/246) of respondents, 24.8% (41/165) of white women, 26.7% (4/15) of Hispanic women, 15.4% (4/26) of Black women, 0.0% (0/4) of East Asian women, 20.0% (1/5) of Southeast Asian women, 50% of South Asian women (3/6) and 20% (5/25) of women of mixed ethnicities. 9.4% (23/246) of all pilot women reported alopecia, highest in Black (26.9%, 7/26) and East Asian women (25%, 1/4). Among women that had a PCOS diagnosis there was a higher presence of clinical hirsutism, higher acne severity, and higher prevalence of alopecia when compared to non-PCOS women. In addition, 33%(4/12) of the 44 women that consented to medical record validation had total testosterone levels above the normal range. CONCLUSIONS: This pilot population demonstrated an ethnic dependent pattern of development for hirsutism, acne and alopecia. Additionally, women who had a PCOS diagnosis were more likely to report having the clinical signs of androgen excess than those without a diagnosis. / 2020-06-14T00:00:00Z

Polycystic ovarian syndrome (PCOS) is the most prevalent female endocrine disorder affecting between 5-15% of women. Characterized by a combination of polycystic ovaries, androgen excess, and abnormal ovulation, untreated PCOS may progress to metabolic abnormalities and increase the risk of adverse health outcomes. Adult PCOS is evaluated using the Rotterdam Consensus Criteria, which requires two of three clinical findings. PCOS is a condition of exclusion, and it is essential to consider differential pathologies before diagnosis. PCOS is a heterogeneous condition, and treatment is fitted to the symptoms that each individual experiences. The physiological effects of PCOS present during puberty, typically around the average age of menarche. The exact etiology of PCOS is unknown, and preventing and curing the condition is not yet possible. Metabolic disturbances caused by PCOS, including insulin resistance and increased blood glucose level, are treated with similar methods as diabetes type 2. Insulin sensitizing agents are used to treat insulin resistance caused by PCOS. The primary treatment for insulin resistance in this population is metformin (Glucophage) due to its relatively safe use and effectiveness in normalizing insulin sensitivity and assisting with normalizing weight. The correlation of PCOS with insulin resistance, central obesity, and metabolic syndrome highlights the importance of diet and exercise supplementation for this population. Weight loss of only 5% in obese and overweight PCOS patients can significantly improve PCOS symptoms, including insulin resistance, androgen levels, and fertility. Exercise alone helps increase the sensitivity of skeletal muscle to insulin and decreases metabolic syndrome risk. The effect of PCOS on the hypothalamic-pituitary-gonadal axis can be detrimental to ovulation and implantation of a fertilized egg. Treatments that suppress the HPG-axis cannot be continued during attempts to become pregnant and throughout pregnancy. Ovulation-inducing agents can improve the rate of ovulation and increase fertility; however, some women may become resistant to these treatments. Clomiphene citrate (Clomid) is often the primary drug used to induce ovulation; however, monotherapy with letrozole has shown greater improvements in pregnancy and live birth rates. Gonadotropins may also be successful treatments, but there is an accompanied increased risk of ovarian hypersensitivity syndrome and multiple pregnancies. Laparoscopic ovarian drilling may help decrease androgen production in the ovary and briefly increase pregnancy capability. During pregnancy, metformin may help decrease the risk of gestational diabetes; however, the long-term effect of fetal exposure to metformin is not well studied. Cosmetic symptoms of PCOS, including hirsutism and acne vulgaris, may cause severe social stress. PCOS women are at additional risk of depression and anxiety. Cosmetic and mental health concerns, combined with the stress caused by the high prevalence of infertility in PCOS, highlight the need for psychological help to be considered in improving the overall quality of life. Combining cognitive behavioral therapy with treatments may help PCOS women maintain treatment and improve their quality of life. The most effective treatment may require modification throughout a patient’s life due to the variance in gonadocorticoid levels throughout a female’s life. Post-menopausal women continue to have excess androgens and estrogens in circulation. High levels of ovarian and adrenal production of gonadocorticoids combined with decreased circulating binding globulins can lead to stress on the metabolic and cardiovascular systems in PCOS after menopause. Continuous levels of increased triglycerides increase the risk for atherosclerosis and adverse cardiac events. PCOS women have an increased risk of endometrial and ovarian cancer, while a link between breast cancer and PCOS is widely disputed. There is 1.66 times higher risk for cardiovascular events, including 1.96 times greater risk for stroke in women with PCOS compared to non-PCOS women when controlled for weight. As we begin to understand the increased risk factors for hypertension, hyperlipidemia, and cardiovascular stress with PCOS, it is crucial to understand how to diagnose and treat PCOS patients in the early stages of the disorder. Irregularities in typical puberty and menarche in adolescents increase the difficulty of diagnosis and may delay a diagnosis.

The phenomenon of platelet hyperaggregability and decreased platelet responsiveness to nitric oxide (also termed as nitric oxide resistance), documented in several cardiovascular disease states, is associated with adverse cardiovascular outcomes. The series of experiments described in this thesis address primarily some aspects of the pathophysiology, epidemiology and therapy of the phenomenon of end-organ resistance to nitric oxide (NO) in two important conditions, that are closely associated with cardiovascular risk factors and disease states:- Polycystic ovary syndrome, which is closely linked with the metabolic syndrome and premature subclinical atherosclerosis. The renin-angiotensin system, which is recognized as a significant mediator in the pathophysiology of a number of cardiovascular disease states. The first study examined the epidemiology/pathophysiology of putative platelet/endothelial dysfunction in young individuals with PCOS. The subsequent studies focused on the potential impact of the renin-angiotensin system on platelet and endothelial function. This mechanistic review is set in the context of a number of recent major clinical studies which have demonstrated surprising efficacy of certain angiotensin-converting enzyme (ACE) inhibitors (ramipril and perindopril) in the prevention of thrombotic processes. Thus we tested the hypothesis whether ACE inhibitor ramipril sensitizes platelets to NO (as a potential mechanism for improved cardiovascular outcomes) in a high risk patient cohort. In addition, particular attention will be given to the emerging role of the heptapeptide Angiotensin- (1-7), a possible physiological antagonist to Angiotensin II in the vasculature and the limitation of the current literature concerning potential effects of the renin-angiotensin system on thrombotic mechanisms. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1348615 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Between 10-15% of women suffer from polycystic ovary syndrome (PCOS), making it the most common cause of female infertility. Clinical features of PCOS include high circulating levels of ovarian androgens (T and A4), anovulation and obesity. The aetiology of this reproductive endocrinopathy is likely to be multifactorial, through the interplay of genetics, epigenetics and environmental factors. Primate research into sexual behaviour development noted that fetally androgenised monkeys developed symptoms like those of PCOS. There are now multiple animal models of PCOS using primates, sheep, rats and transgenic mice. The investigations described in this thesis use rodent models to examine the role of androgens in the pathogenesis of female infertility. An attempt to generate a granulosa cell specific androgen receptor knockout mouse model will first be described, followed by several studies into the developmental programming of female Wistar rat infertility and metabolism by steroid hormones. Initial investigations showed that testosterone proprionate (TP) administered to female rats during different windows of fetal and neonatal life alters the reproductive and metabolic axes of the adult animals. Fetal plus neonatal TP exposure led to complete ovarian dysgenesis, while postnatal exposure produced a PCOS-like phenotype. Animals which received TP postnatally were heavier and had an increased proportion of primordial follicles in their ovaries by postnatal day (pnd) 90 of life. Evaluation of this PCOS model showed that neonatally androgenised rats had ovarian follicles with larger antra and a greater ovarian stromal compartment. In addition, these animals were heavier when compared to controls. However, unlike human studies, neonatally androgenised rats showed no differences in circulating gonadotrophin or ovarian androgen levels. Nor did they show any programming effect of neonatal TP upon the theca interna by pnd 90. Further investigations to narrow the windows and dose of TP required to produce a PCOS phenotype showed that TP administered in an early window of neonatal life, between postnatal days (pnd) 1-6 not only led to anovulation, but potentially reprogrammed the hypothalamic-pituitary axis, as there was minimal gonadotrophin response to reduced ovarian negative feedback (inhibin B and estradiol) in these rats. Neonatal TP also affected the rat metabolic axis with adult animals becoming heavier after weaning without any change in food intake. Animals developed mesenteric and retroperitoneal obesity along with insulin resistance (IR). Increased hepatic glucocorticoid turnover and altered adipokine expression were also noted in neonatally androgenised females, possibly contributing to the pathogenesis of obesity. No effect of TP dose upon the severity of infertility or metabolic abnormalities in adult animals was observed. To delineate which features of the rat PCOS model resulted from androgenic, estrogenic or corticosteroid action, a final study used administration of different steroids during the early window of postnatal life: TP, estradiol valerate (EV), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and dexamethasone (DEX). The anovulatory PCO-like phenotype observed with TP was also seen in animals which received EV, but not those which received DHT, DHEA or DEX. TP and EV treatment also resulted in a reduction of ovarian follicle numbers and activated follicle proportions, with an increase in primordial follicle proportions. Although glucose tolerant, animals treated with TP and EV were highly IR. Unlike dexamethasone, DHT and DHEA also produced IR in adult animals, to a lesser extent than TP and EV. Taken collectively, the results described in this thesis demonstrate that the PCOS-like phenotype observed in the neonatally androgenised female rat is likely to be due to the estrogenic actions of testosterone, potentially through as yet unknown epigenetic mechanisms. The programming of the metabolic components described may additionally be due to the actions of androgens. Furthermore, these studies demonstrate a novel estrogenic effect of neonatal steroids upon primordial follicle populations and show that the neonatally androgenised rat may be a rational PCOS model in a poly-ovulatory species.

Polycystic ovary syndrome (PCOS) is a common reproductive, endocrine and metabolic disorder present in women of reproductive age. Despite the widespread prevalence and heritability of PCOS, the heterogeneous and polygenic traits have made the successful identification of candidate genes difficult. Animal models have been developed on the premise that early exposure to sex steroids can programme epigenetic changes that predispose the fetus to the adult features of PCOS. Past research has modelled ovarian dysfunction, endocrine abnormalities and metabolic perturbances in rodent, non-human primate and sheep PCOS models, through the enhanced neonatal or prenatal exposure to the male sex hormone, testosterone. The modelling of PCOS in a large domestic species such as the sheep is advantageous due to similar biological reproductive function as the human. In this regard the sheep has been extensively used to model PCOS by the treatment of pregnant ewes from early to midgestation with androgens such as testosterone propionate (TP). These experiments have demonstrated the fetal programming effects of androgens on offspring that go on to develop PCOS-like characteristics in adulthood. One of the caveats of assessing steroid effects in this way is the effect of the placenta in mediating the transfer of these hormones. TP is an aromatisable androgen and thus some of its effects in the fetus may be attributable to placental by-products such as estrogens. This thesis describes the development and assessment of a novel model of prenatal androgenisation. Two models were compared: the indirect maternal exposure to TP (the current model) and the direct fetal injection of TP. In directly treating the fetus this allowed control over the dose of TP administered and avoidance of secondary effects that androgens may exert in the mother that could be transferred to the fetus. For the maternal model, pregnant Scottish Greyface ewes were administered TP twice weekly from day (d)62-102 of a 147 day gestation. For the fetal model, fetuses were injected twice while the ewe was anaesthetised with graded doses of TP during the same period of treatment as the maternal model. The effects of prenatal androgenisation were assessed in the female fetus shortly after treatment and also in young adult sheep. Fetal ovarian and adrenal steroidogenic gene expression was monitored and found to be altered in response to elevated levels of sex steroids. At d90 the morphology of the developing ovary was not changed by prenatal androgens. In the adult a detailed ovarian and endocrine assessment was undertaken, by examination of ovarian morphology, hormone levels, ovulatory cycles, hypothalamic pituitary ovarian function and follicle steroidogenesis, during the first breeding season. In addition, the metabolic effects of prenatal androgens were monitored by measuring body fat, insulin and glucose homeostasis and liver function. Neither maternal nor fetal prenatal androgenisation during mid-gestation resulted in a perturbed hormonal milieu or polycystic ovaries in young adults. These treatments did however programme a clear ovarian phenotype demonstrated by the increased capacity of follicles to secrete androgens, independently of an abnormal endocrine environment and disordered folliculogenesis. Furthermore, animals that were exposed maternally to TP developed fatty liver and had increased insulin secretion in response to glucose load. A major outcome of this study was the finding that the fetally injected control animals were phenotypically different than the maternal control animals. In fact, some of the reproductive and metabolic features of maternal TP exposure were found in the fetal control group. This unexpected finding has raised the possibility that it is the fetal exposure to stress, that is secondary to elevated maternal androgens, rather than androgens per se that is responsible for at least some of the multitude of anomalies encountered in PCOS.

Class of 2006 Abstract / Objectives: To determine if Polycystic Ovarian Syndrome (PCOS) patients treated with lifestyle changes and metformin resulted in ovulation after six months of treatment. Methods: A retrospective chart review of initial patient visits at an infertility clinic were obtained. Patients that were given a diagnosis of PCOS were further reviewed for age at initial diagnosis, weight, height, ovarian cysts, lifestyle recommendations (diet, exercise, and vitamin use), metformin recommendations and usage, and if ovulation occurred after six months of treatment. Results: A total of 1011 charts were reviewed. At the initial office visit, 206 (20.38%) of these patients were classified as having PCOS. Of PCOS patients, 113 (54.85%) patients ovulated after six months of treatment. In the average initial weight, ovulators averaged slightly less weight than did non-ovulators (171.77 pounds ± 44.26 vs. 188.65 pounds ± 51.37, p=0.0121). This also follows true for the initial BMI of ovulators vs. non-ovulators (29.53 kg/m2 ± 10.14 vs. 32.69 kg/m2 ± 13.03, p=0.0521). There was a significant difference in metformin use between ovulators and non-ovulators (90.27% vs. 73.12%, p=0.0024). More ovulators were found to continue metformin treatment as compared to non-ovulators. Conclusions: In this specific infertility clinic setting, 20.3% of patients were diagnosed with PCOS at the initial office visit. Of these PCOS patients, treatment with lifestyle changes and metformin use resulted in 55% of patients achieving ovulation at six months. This study shows that weight loss, through lifestyle modification and metformin treatment, increases this population’s chances of ovulation within six months of therapy.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy disorder in reproductive age women. The symptoms of this disorder are the androgen excess seen with anovulation/oligoovulation or morphologically ovarian cysts. The aim of the study was to assess the efficacy of public health nutrition intervention designed to enhance healthy eating and lifestyle modification among PCOS patients attended the obstetrics and gynecology clinic at the American University of Beirut Medical Centre (AUB-MC) in Beirut, Lebanon. A prospective hospital based public health nutrition intervention was proposed in which 76 women with PCOS were recruited in the pilot study and 588 women were recruited in the scale-up intervention divided between PCOS and non-PCOS. During the scale up phase non-PCOS women were recruited to study the effect of the nutritional counseling on them as a way to compare the outcome with PCOS women. Recruited population were divided into 8 groups; group A: overweight/obese PCOS patient’s intervention (received weight management program with nutritional guidelines). Group B: overweight/ obese PCOS controls (received the usual heath care by the gynecologist), Group C: lean PCOS controls (received the usual heath care by the gynecologist), Group D: lean PCOS intervention (received weight maintenance program with nutritional guidelines ), Group E: overweight/obese non-PCOS patient’s intervention (received weight management program with nutritional guidelines) ,Group F: overweight/ obese non-PCOS controls, Group G: lean non- PCOS intervention (received weight maintenance program with nutritional guidelines), Group H: lean non-PCOS controls. Data were collected using a pre-validated questionnaire to capture sociodemographic variables, nutritional status, and physical activity, psychological and medical status. Blood analysis was carried out to determine biochemical indices. Assessment of study indicators were carried out at baseline, after 3 and 6 months from inception of intervention (pilot as well scale up). Patients in intervention groups attended a 6 month tailored nutrition counseling/education program (2 sessions per month), to enhance their understanding of their dietary intake and assist them with weight management, physical activity, healthy cooking, lifestyle, and food shopping. Following a six months pilot study intervention results have shown that 7% weight loss was achieved in overweight/ obese intervention groups and weight maintenance in lean intervention groups( Group A,B,C and D). There was a significant reduction in waist (-4.2 cm (±5.6)) and hip circumference (-3.1cm (±3.5)) with P < 0.001. There was no significant biochemical markers change (fasting blood sugar, CRP, LDL-C,HDL-C,TG,total cholesterol, fasting insulin, total testosterone,Vit D), however there was an increase in physical activity (3.1 hours/week (±1.5)) , and decrease in anxiety and depression score ( BDI-II and BAD-7); -0.8 (±0.8) and -0.7 (±0.7) with P < 0,001 compared to interventions. Following six months scale up intervention, the results have shown a weight reduction among overweight/obese PCOS women (group A) who lost, on average, 8.2 kg (P=0.001). Whilst non-PCOS women lost, on average 11.6 kg (P < 0.001)(Group E). Controls gained weight (Group B, D F and H). The biochemical, psychological and reproductive profile showed significant improvements among PCOS women (P < 0.001). Pregnancy rate increased to 70% among women trying to conceive. The results of this study have shown this intervention to be effective in Lebanese women with PCOS, decreasing their initial body weight by 5%- 10% and improving their reproductive, metabolic and endocrine profiles. This suggests the need for a nutritional intervention (nutritional guidelines) for women diagnosed with PCOS patients as a first line treatment. The study results support the effectiveness of lifestyle modification diet for PCOS women.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility and the most common endocrinopathy of women of reproductive age. Genome-wide association studies (GWAS) identified a number of loci associated PCOS in different ethnic populations, including women with Asian and European ancestry. Replication studies have confirmed some of these associations. Among the loci identified are those located near the LH receptor gene (LHCGR), a clathrin-binding protein gene (DENND1A) that also functions as a guanine nucleotide exchange factor, and the gene encoding RAB5B, a GTPase and protein involved in vesicular trafficking. The functional significance of one of these GWAS candidates (DENND1A) was supported by our discovery that a truncated protein splice variant of DENND1A termed DENND1A.V2, is elevated in PCOS theca cells, and that forced expression of DENND1A.V2 in normal theca cells increased CYP11A1 and CYP17A1 expression and androgen synthesis, a hallmark of PCOS. We previously proposed that the PCOS GWAS loci could be assembled into a functional network that contributes to altered gene expression in ovarian theca cells, resulting in increased androgen synthesis. Here we demonstrate the localization of LHCGR, DENND1AV.2 and RAB5B proteins in various cellular compartments in normal and PCOS theca cells. hCG and forskolin stimulation affects the distribution and co-localization of DENND1A.V2 and RAB5B in various cellular compartments This cytological evidence supports our PCOS gene network concept, and raises the intriguing possibility that LHCGR activation, via a cAMP-mediated process, promotes the translocation of DENND1A.V2 and RAB5B-containing vesicles from the PCOS theca cell cytoplasm into the nucleus, resulting in increased transcription of genes involved in androgen synthesis.