The effects of metformin and rosiglitazone, alone and in combination, on the ovary and endometrium in polycystic ovary syndrome

Legro, Richard S.; Zaino, Richard J.; Demers, Laurence M.; Kunselman, Allen R.; Gnatuk, Carol L.; Williams, Nancy I.; Dodson, William C.

doi:10.1016/j.ajog.2006.12.025

Cited by 87 publications

(53 citation statements)

References 37 publications

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“…Another study by Mitkov et al reported a greater reduction in androgens in metformin treatment arm, while rosiglitazone was more potent in improving IR and hyperinsulinemia (47). Legro et al showed that rosiglitazone was more efficient than metformin in reducing elevated insulin and androgen levels in an obese PCOS population (48). In our patients, both drugs were equally effective in reducing androgen levels, fasting insulin levels and HOMA IR score, while an improvement of GLUT4 expression was more pronounced with rosiglitazone treatment.…”

Section: Discussionmentioning

confidence: 62%

Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome.

Jensterle

Janež

Mlinar

et al. 2008

European Journal of Endocrinology

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Objective: The insulin-resistant state of the polycystic ovary syndrome (PCOS) was found to be associated with a decreased glucose transporter GLUT4 expression in the insulin target tissues. This study was performed to explore whether the well-known clinical, hormonal and metabolic efficacy of metformin or rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA expression in patients with PCOS.

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Section: Discussionmentioning

confidence: 62%

Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome.

Jensterle

Janež

Mlinar

et al. 2008

European Journal of Endocrinology

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“…These morphological changes mimic some of those seen in women with PCOS. Although the mechanisms by which rosiglitazone improves fertility in women with PCOS are not fully understood, it is thought to reduce androgen production [24,34], decrease oxidative stress, and increase insulin sensitivity [35]. The more recently discovered EG-VEGF has also been linked to PCOS, and is thought to synergize with VEGF in stimulating new ovarian vessel growth in this disease [15].…”

Section: Discussionmentioning

confidence: 96%

Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine

Petrik

Gerstein

Cesta

et al. 2009

Endocr

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We have previously shown that in utero nicotine exposure causes impaired fertility, follicle immaturity, and ovarian dysfunction in adult female rat offspring. These characteristics overtly resemble the clinical profile of polycystic ovarian syndrome (PCOS) and recent studies have shown that thiazolidinediones such as rosiglitazone improve fertility in women with PCOS but the mechanism is not well defined. Our goal was to examine whether rosiglitazone would (1) ameliorate the altered ovarian physiology that occurs following fetal and neonatal exposure to nicotine and (2) to examine whether this could be due to normalization of ovarian vascularization. At weaning, offspring of nicotine-exposed dams were given either vehicle (NV) or rosiglitazone (3 mg kg(-1) day(-1); NR). Offspring of saline-exposed dams received vehicle (SV). Tissues were collected when the female offspring reached 26 weeks of age. NV animals had reduced granulosa cell proliferation and increased ovarian cell apoptosis. Treatment with rosiglitazone increased proliferation, and decreased apoptosis, compared NV animals. NV animals had decreased ovarian vascularity relative to controls, whereas NR animals had an intermediate level of ovarian vessel density. Moreover, ovaries from NV animals had decreased levels of the pro-angiogenic growth factors vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF both of which were increased with rosiglitazone treatment. Rosiglitazone reversed some of the nicotine effects in the ovary and increased ovarian vascularization, follicle maturation and improved oocyte competence. Rosiglitazone may be an important treatment option for PCOS and the present study provides a potential mechanism by which rosiglitazone may have beneficial effects on fertility in these patients.

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“…In particular, patients with simple hyperplasia or adenocarcinoma at baseline showed no evidence of abnormal histology after 6 months of insulin-sensitizing therapy. Unfortunately, in this last study (330), the distinction between the beneficial effects of the drug due to the ovarian function improvement/restoration and the direct effects of the drug on the endometrium itself remained unclear.…”

Section: B Cancer Implicationsmentioning

confidence: 99%

“…Notwithstanding these theoretical mechanisms, prospective studies providing clinical data are very few (329,330).…”

Section: B Cancer Implicationsmentioning

confidence: 99%

Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review

et al. 2008

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Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus. Because many women with polycystic ovary syndrome (PCOS) are insulin resistant, metformin was introduced in clinical practice to treat these patients also. Moreover, metformin's effect has other targets beside its insulin-sensitizing action. The present review was aimed at describing all evidence-based and potential uses of metformin in PCOS patients. In particular, we will analyze the uses of metformin not only for the treatment of all PCOS-related disturbances such as menstrual disorders, anovulatory infertility, increased abortion, or complicated pregnancy risk, hyperandrogenism, endometrial, metabolic and cardiovascular abnormalities, but also for the prevention of the syndrome. (Endocrine Reviews 30: 1-50, 2009)

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The effects of metformin and rosiglitazone, alone and in combination, on the ovary and endometrium in polycystic ovary syndrome

Cited by 87 publications

References 37 publications

Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome.

Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome.

Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine

Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review

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