Treatment of infertility in women with polycystic ovary syndrome

Bouchard, Philippe

doi:10.1016/j.ando.2010.03.006

Cited by 7 publications

(9 citation statements)

References 15 publications

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“…Raised plasma insulin levels are now recognized as a feature of PCOS, and hyperinsulinism has been shown to contribute to ovarian overproduction of androgens [4]. The exact mechanism through which metformin acts in PCOS is still unknown and thus the variable effects that are seen are not explicable [2]. Its various mechanisms of action include inhibition of gluconeogenesis in the liver and stimulation of peripheral uptake of glucose [5].…”

Section: Introductionmentioning

confidence: 98%

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Metformin Decreases GnRH- and Activin-Induced Gonadotropin Secretion in Rat Pituitary Cells: Potential Involvement of Adenosine 5' Monophosphate-Activated Protein Kinase (PRKA)

Tosca

Froment

Ramé

et al. 2010

Biology of Reproduction

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Metformin is an insulin sensitizer molecule used for the treatment of infertility in women with polycystic ovary syndrome and insulin resistance. It modulates the reproductive axis, affecting the release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). However, metformin's mechanism of action in pituitary gonadotropin-secreting cells remains unclear. Adenosine 5' monophosphate-activated protein kinase (PRKA) is involved in metformin action in various cell types. Here, we investigated the effects of metformin on gonadotropin secretion in response to activin and GnRH in primary rat pituitary cells (PRP), and studied PRKA in rat pituitary. In PRP, metformin (10 mM) reduced LH and follicle-stimulating hormone (FSH) secretion induced by GnRH (10(-8) M, 3 h), FSH secretion, and mRNA FSHbeta subunit expression induced by activin (10(-8) M, 12 or 24 h). The different subunits of PRKA are expressed in pituitary. In particular, PRKAA1 is detected mainly in gonadotrophs and thyrotrophs, is less abundant in lactotrophs and somatotrophs, and is undetectable in corticotrophs. In PRP, metformin increased phosphorylation of both PRKA and acetyl-CoA carboxylase. Metformin decreased activin-induced SMAD2 phosphorylation and GnRH-induced mitogen-activated protein kinase (MAPK) 3/1 (ERK1/2) phosphorylation. The PRKA inhibitor compound C abolished the effects of metformin on gonadotropin release induced by GnRH and on FSH secretion and Fshb mRNA induced by activin. The adenovirus-mediated production of dominant negative PRKA abolished the effects of metformin on the FSHbeta subunit mRNA and SMAD2 phosphorylation induced by activin and on the MAPK3/1 phosphorylation induced by GnRH. Thus, in rat pituitary cells, metformin decreases gonadotropin secretion and MAPK3/1 phosphorylation induced by GnRH and FSH release, FSHbeta subunit expression, and SMAD2 phosphorylation induced by activin through PRKA activation.

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Section: Introductionmentioning

confidence: 98%

“…Metformin is an insulin-sensitizing drug, introduced for the treatment of anovulatory infertility in polycystic ovary syndrome (PCOS) patients with glucose intolerance and/or insulin resistance [1] but with varying degrees of success [2]. PCOS affects 5%-10% of women of childbearing age [3].…”

Section: Introductionmentioning

confidence: 99%

Metformin Decreases GnRH- and Activin-Induced Gonadotropin Secretion in Rat Pituitary Cells: Potential Involvement of Adenosine 5' Monophosphate-Activated Protein Kinase (PRKA)

Tosca

Froment

Ramé

et al. 2010

Biology of Reproduction

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“…[228][229][230] Treatment of PCOS and associated hyperandrogenism and hyperinsulinemia has been the subject of several recent reviews. [231][232][233][234] Aromatase inhibitors in particular appear to be superior compared with clomiphene citrate in this condition, [235][236][237] although controlled trials for RPL are limited. In ovulatory women with PCOS, endometriosis can be a cofactor because many women with heavy irregular bleeding would be at risk for development of endometriosis.…”

Section: Management Of Endometrial Receptivity Defects In Recurrent Pmentioning

confidence: 99%

Clinical Assessment and Management of the Endometrium in Recurrent Early Pregnancy Loss

Patel

Lessey

2011

Semin Reprod Med

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Unexplained and recurrent loss of pregnancies is a heartbreaking and frustrating condition. The routine diagnostic workup for pregnancy loss includes hormonal evaluation, screening for genetic or chromosomal defects, immunologic and thrombophilic testing, and evaluation of congenital or acquired Müllerian defects. In cases of idiopathic pregnancy loss, defects in endometrial receptivity are increasingly being investigated. The role of the endometrium in pregnancy loss has historical roots but remains controversial. Exciting new directions based on microRNAs, proteomics, and epigenetics promises to keep this area of investigation both interesting and complex. With each new diagnostic and therapeutic biomarker identified comes a greater potential for diagnosis and treatment of women. The clinical assessment of the endometrium remains an important part of the investigation of couples with unexplained pregnancy loss.

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“…The infertility management of these women can range from medical therapy (ovulation induction), surgical techniques (laparoscopy ovarian drilling) to the use of assisted reproduction techniques (ART) (2,7) .…”

Section: Introductionmentioning

confidence: 99%

“…For these patients, the first recommendation is lifestyle changes (2,7,8) . Because most of the patients are overweight, a 5 percent of weight loss can improve the outcome.…”

Section: Introductionmentioning

confidence: 99%

Mono ovulation in women with polycystic ovary syndrome - outcomes of different therapies

Luchian¹,

Luchian²,

Marinescu³

2017

Ginecologia.ro

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Inducerea monoovulației la pacientele cu sindromul ovarelor micropolichisticerezultatele terapiilor disponibile Ovulation induction is the first line of treatment for in ferti lity in women diagnosed with polycystic ovary syndrome and with no other cause of infertility. Clomi phene citrate is the most frequently used pharmacological agent. A pros pective study was conducted to evaluate different ovu lation induction agents (clomiphene citrate, letrozole, re com binant FSH) outcomes in 60 patients diagnosed with this syndrome. The study showed similar re sults from letrozole and clomiphene citrate in ovulation in duction and pregnancy, but recombinant FSH had the best results.

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Treatment of infertility in women with polycystic ovary syndrome

Cited by 7 publications

References 15 publications

Metformin Decreases GnRH- and Activin-Induced Gonadotropin Secretion in Rat Pituitary Cells: Potential Involvement of Adenosine 5' Monophosphate-Activated Protein Kinase (PRKA)

Metformin Decreases GnRH- and Activin-Induced Gonadotropin Secretion in Rat Pituitary Cells: Potential Involvement of Adenosine 5' Monophosphate-Activated Protein Kinase (PRKA)

Clinical Assessment and Management of the Endometrium in Recurrent Early Pregnancy Loss

Mono ovulation in women with polycystic ovary syndrome - outcomes of different therapies

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