Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial

Kar, S.

doi:10.4103/0974-1208.106338

Cited by 78 publications

(75 citation statements)

References 20 publications

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“…These findings are in agreement with clinical evidence supporting a direct role for androgen actions in the development of dysfunctional menstrual cycling and ovulation in PCOS, as prolonged treatment with the AR antagonist flutamide is reported to restore menstrual-cycle regularity and ovulation in some women with PCOS (15,29). Interestingly, by contrast, the treatment of women with PCOS with estrogen blockage, either by antiestrogen (clomiphene citrate) or an aromatase inhibitor (letrozole) that increases FSH secretion, is rapidly effective at inducing ovulation (30). This implies that the hypothalamic-pituitary feedback response in PCOS women is functional but that the longer time to effective treatment by androgen blockade may involve more complex, possibly multistep underlying mechanisms of androgen-mediated effects, compared with the more direct mode of action of estrogen blockade.…”

Section: Discussionsupporting

confidence: 71%

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

Caldwell

Edwards

Desai

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

177

185

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Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanismbased treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS.PCOS | androgen | animal model | neuroendocrine P olycystic ovary syndrome (PCOS) is the most frequent endocrine disorder of young women, with a prevalence of 6 to 15% (1), and accounts for more than 75% of anovulatory infertility (2). It is characterized by reproductive hormone dysregulation involving luteinizing hormone (LH) hypersecretion and hyperandrogenism (3), the consequences of which can be acne and hirsutism, as well as reduced fertility, due to aberrant follicular maturation, ovulatory disturbance, and miscarriage (3). Associated nonreproductive abnormalities, such as obesity, metabolic syndrome, hyperinsulinemia, insulin resistance, hepatic steatosis, and dyslipidemia predispose affected women to heightened risk of cardiovascular disease and type 2 diabetes (3, 4). However, despite the high prevalence and significant health impact, the pathogenesis of PCOS remains unclear so that mechanism-based treatments remain unattainable.Hyperandrogenism, the most consistent feature of PCOS (5), is implicated as a key mediator in the pathogenesis of PCOS. Supportive evidence includes that androgen excess from endogenous [congenital adrenal hyperplasia (6)] or exogenous [female-to-male transsexuals (7)] sources can produce polycystic ovaries. Furthermore, androgens induce reproductive, metabolic, and endocrine features of PCOS in rodent, sheep, and primate animal models of PCOS (8-10). As all androgen action is mediated via the androgen receptor (AR),...

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Section: Discussionsupporting

confidence: 71%

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

Caldwell

Edwards

Desai

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

177

185

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“…Metformin does not have an effect on the biochemical parameters of FSH, LH. This differs from some studies showing that metformin reduces the effect of LH and causes an elevation in serum FSH [29] [30] and agreed with studies showing that metformin has no effect on hormonal parameters [20] [31] [32]. Historically, the overall successful pregnancy rates after ovulation induction range from as low as 9% to as high as 25% [33].…”

Section: Discussioncontrasting

confidence: 53%

Comparative Study between Metformin and Laparoscopic Ovarian Drilling for Ovulation Induction, Achievement of Pregnancy and Live Birth in Asian Women with Polycystic Ovarian Syndrome: A Prospective Trial

Jahan¹,

Nayer²,

Habib³

et al. 2014

OALib

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Objective: To compare the efficacy of metformin and laparoscopic ovarian drilling to be used in anovulatory patients with polycystic ovarian syndrome (PCOS) for ovulation induction and pregnancy achievement. Materials and Methods: Setting and Design: A prospective clinical trial conducted in the outpatient department of Gynaecology and Obstetrics of BIRDEM hospital from August 2008 to August 2013. Patient(s): Three hundred and eight newly diagnosed patients with PCOS based on ESHRE/ASRM criteria. These patients were assigned to two groups: Group 1 (152 patients) received 500 mg of metformin three times a day; Group 2 (156 patients) received laparoscopic ovarian drilling. Main Outcome Measure(s): Rate of ovulation, pregnancy rate (PR), and live birth. Ovulation was monitored by serum progesterone, transvaginal sonography up to six cycles or till pregnancy occurred upto six months. Result(s): The ovulation rate was 68.4% in the metformin group, 59% in the laparoscopy treatment group. The pregnancy rate was (20.1% and 16.6%) and live birth rate was (18.4% and 15.4%) in metformin and laparoscopy treatment groups, respectively. The rate of spontaneous first trimester loss was three and two in metformin and laparoscopy group respectively. There were no ectopic pregnancies in metformin group and two in laparoscopy group. There was no second trimester pregnancy loss in metformin group, three in laparoscopy group. There were no multiple pregnancies in metformin group, two in lapa-* Corresponding author. S. Jahan et al.OALibJ |

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“…However, clinical trials of aromatase inhibitors for PCOS yield controversial results regarding pregnancy rates (Badawy et al 2009, Kar 2012, Roy et al 2012). The present study has shown that aromatase expression in luteinized granulosa cells is down-regulated by high testosterone in PCOS patients.…”

Section: Discussionmentioning

confidence: 99%

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Yang¹,

Ruan²,

Yang³

et al. 2015

Reproduction

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Women with polycystic ovary syndrome (PCOS) undergoing IVF-embryo transfer based-assisted reproductive technology (ART) treatment show variable ovarian responses to exogenous FSH administration. For better understanding and control of PCOS ovarian responses in ART, the present study was carried out to compare the follicular hormones and the expression of granulosa cell genes between PCOS and non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138 PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid collected from PCOS women showed high levels of testosterone. The expression of aromatase was found significantly reduced in luteinized granulosa cells from PCOS women. In cultured luteinized granulosa cells isolated from non-PCOS women, their exposure to testosterone at a level that was observed in PCOS follicles could decrease both mRNA and protein levels of aromatase in vitro. The inhibitory effect of testosterone was abolished by androgen receptor antagonist, flutamide. These results suggest that the hyperandrogenic follicular environment may be a key hazardous factor leading to the down-regulation of aromatase in PCOS.Reproduction (2015) 150 289-296

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Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial

Cited by 78 publications

References 20 publications

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

Comparative Study between Metformin and Laparoscopic Ovarian Drilling for Ovulation Induction, Achievement of Pregnancy and Live Birth in Asian Women with Polycystic Ovarian Syndrome: A Prospective Trial

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

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