Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome

Kashyap, Sonya; Wells, George A.; Rosenwaks, Zev

doi:10.1093/humrep/deh440

Cited by 128 publications

(71 citation statements)

References 38 publications

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“…Met improves maternal metabolism [6,[68][69][70][71][72][73][74][75][76] and ovulation [68,77] and is good for oocytes and embryos derived from females under obese and diabetic conditions [23][24][25]78], and thus, AMPK can improve compromised oocytes and embryos. CC alone increases Oct4, suggesting that Fig.…”

Section: Discussionmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

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Purpose The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3, 3′-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development. Methods The methods used were as follows: culture post-thaw mouse zygotes to the two-cell embryo stage and test effects after 1-h AMPK agonists' (e.g., Met, Asa, BR-DIM, control hyperosmotic stress) exposure on AMPK-dependent loss of Oct4 and/or Rex1 nuclear potency factors, confirm AMPK dependence by reversing potency loss in two-cell-stage embryos with AMPK inhibitor compound C (CC), test whether Met + Asa (i.e., co-added) or DS BR-DIM decreases development of two-cell to blastocyst stage in an AMPK-dependent (CCsensitive) manner, and evaluate the level of Rex1 and Oct4 nuclear fluorescence in two-cell-stage embryos and rate of two-cell-stage embryo development to blastocysts. Result(s) Met, Asa, BR-DIM, or hyperosmotic sorbitol stress induces rapid~50-85 % Rex1 and/or Oct4 protein loss in twocell embryos. This loss is~60-90 % reversible by co-culture with AMPK inhibitor CC. Embryo development from twocell to blastocyst stage is decreased in culture with either Met + Asa or BR-DIM, and this is either >90 or~60 % reversible with CC, respectively. Conclusion These experimental designs here showed that Met-, Asa-, BR-DIM-, or sorbitol stress-induced rapid potency loss in two-cell embryos is AMPK dependent as suggested by inhibition of Rex1 and/or Oct4 protein loss with an AMPK inhibitor. The DS BR-DIM or fertility drugs (e.g., Met + Asa)Capsule Drugs metformin and aspirin and diet supplement BR-DIM cause AMPK-dependent potency loss and decrease embryonic development from two-cell to blastocyst stage. Reprod Genet (2016) 33:1027-1039 DOI 10.1007 that are used to enhance maternal metabolism to support fertility can also chronically slow embryo growth and block development in an AMPK-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

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“…Most importantly, however, the majority of studies have shown that metformin may significantly improve menstrual cycles and ovulation rates, both spontaneous and clomipheneinduced. Several recent reviews covering all aspects of metformin therapy are available and readers may refer to these for more detailed information (46)(47)(48)(49). In a recent meta-analysis performed by Lord et al (47,48), the effectiveness of metformin in improving clinical and biochemical features of PCOS was assessed.…”

Section: Metforminmentioning

confidence: 99%

Insulin-sensitizing agents in polycystic ovary syndrome

Pasquali

Gambineri

2006

eur j endocrinol

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Insulin-sensitizing agents have been recently proposed as the therapy of choice for polycystic ovary syndrome (PCOS), since insulin resistance and associated hyperinsulinemia are recognized as important pathogenetic factors of the syndrome. Moreover, since almost all obese PCOS women and more than half of those of normal weight are insulin resistant, and therefore present some degree of hyperinsulinemia, the use of insulin sensitizers should be suggested in most patients with PCOS. Insulin sensitizer treatment has been associated with a reduction in serum androgen levels and gonadotropins, and with an improvement in serum lipids and in prothrombotic factor plasminogenactivator inhibitor type 1, whatever the insulin sensitizer used. This therapy has also been associated with a decrease in hirsutism and acne, and with a regulation of menses and an improvement of ovulation and fertility. Notable improvements in all these parameters have also been described after a change in lifestyle approach, particularly in the presence of obesity. Lifestyle interventions should therefore be combined with insulin sensitizers in PCOS when obesity is present.

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“…Metformin is a biguanide class of oral antidiabetic whose work is increasing insulin sensitivity in peripheral tissues so that the decrease in insulin will reduce ovarian androgen production and an increase in SHBG so that the amount of free androgens will decrease and improves menstrual cycle and ovulation. Metformin is 50% better than placebo in the induction of ovulation in PCOS patients (RR 1:50; 95% CI 1.13-1.99) and also can improve menstrual cycles compared to placebo (RR 1:45; 95% CI 1.11-1.90) (Kashyap et al 2004). Systematic review and metaanalysis of 13 studies randomized control trial demonstrated the effectiveness of metformin in improving clinical and biochemical profiles in PCOS.…”

Section: Introductionmentioning

confidence: 96%

Analysis of Homa-Ir, Follicle Size, and Estradiol After Combination Therapy of Metformin and Clomiphene Citrate in Polycystic Ovary Syndrome’s Patient

Dzykryanka¹,

Yulistani²,

Santoso³

2016

FMI

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Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome

Abstract: Metformin is effective for ovulation induction and cycle regulation in this group of patients. Metformin plus CC appears to be very effective for achievement of pregnancy compared to CC alone. No RCTs directly compare metformin to CC but the need for such a trial exists.

Cited by 128 publications

References 38 publications

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Insulin-sensitizing agents in polycystic ovary syndrome

Analysis of Homa-Ir, Follicle Size, and Estradiol After Combination Therapy of Metformin and Clomiphene Citrate in Polycystic Ovary Syndrome’s Patient

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