Metformin or Antiandrogen in the Treatment of Hirsutism in Polycystic Ovary Syndrome

Harborne, L; Fleming, Richard; Lyall, Helen; Sattar, Naveed; Norman, Jane E.

doi:10.1210/jc.2003-030424

Cited by 174 publications

(107 citation statements)

References 31 publications

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“…Metformin significantly improved hirsutism in the current study, similar to both OCP groups, despite differential effects on androgen levels. One previous controlled study (2,25) reported the effects of metformin on hirsutism, demonstrating greater efficacy with metformin than with high-dose OCP. Potential mechanisms of action include improved IR and/or IGF-I activity, each of which are affected by metformin and involved in hair growth (25).…”

Section: Conclusion -In Women Withmentioning

confidence: 99%

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

2007

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OBJECTIVE -We aimed to determine the impact of medical therapy for symptom management on insulin resistance, metabolic profiles, and surrogate markers of cardiovascular disease in polycystic ovary syndrome (PCOS), an insulin-resistant pre-diabetes condition. RESULTS -All treatments similarly and significantly improved symptoms including hirsutism and menstrual cycle length. Insulin resistance was improved by metformin and worsened by the high-dose OCP. Arterial stiffness worsened in the higher-dose OCP group (PWV 7.46 vs. 8.03 m/s, P Ͻ 0.05), related primarily to the increased insulin resistance. RESEARCH DESIGN AND METHODS -One hundred overweight women (BMI Ͼ27kgCONCLUSIONS -In overweight women with PCOS, metformin and low-and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function. These findings suggest that a low-dose OCP preparation may be preferable if contraception is needed and that metformin should be considered for symptomatic management, particularly in women with additional metabolic and cardiovascular risk factors. Diabetes Care 30:471-478, 2007I t is well recognized that polycystic ovary syndrome (PCOS) has both reproductive and metabolic features. Insulin resistance (IR), the primary underlying abnormality, affects the majority of women with PCOS (1,2). In general populations, IR independently predicts cardiovascular risk (3,4), underlies the metabolic syndrome, and increases the risk of type 2 diabetes (1,2).Type 2 diabetes also potently increases cardiovascular risk, especially in women. Furthermore, treating IR improves the metabolic profile, reduces progression to type 2 diabetes, and decreases cardiovascular risk in general populations. In PCOS, IR is increased, cardiovascular risk factors are elevated, type 2 diabetes risk is increased four-to sevenfold, and the risk of cardiovascular disease is also likely to be increased (2,5). We postulate that IR per se is an important target in the treatment of this condition, especially when considering long-term health implications in PCOS.Lifestyle modification is first-line therapy for IR in PCOS, and a loss of 5-10% of body weight improves IR and increases ovulation (6,7). As long-term weight loss is not feasible or sustainable in the majority (8), additional medical therapy is usually required. The oral contraceptive (OCP) is first-line medical therapy in PCOS, when fertility is not desired, in regulating cycles and controlling hyperandrogenism. Yet, in both PCOS and non-PCOS populations, the OCP increases IR, albeit inconsistently (1,9 -12).The increased IR appears to be estrogen dose related (13,14). The metabolic effects of OCP preparations have not been adequately studied in PCOS, and optimal preparations and doses remain unclear.Alternatively, medical therapy can directly target IR in PCOS. Glitazones are considered inappropriate in reproductive-age women until concerns over teratogenicity are clarified (1). Metformin, supported by a Cochrane review (15), has a legitimate adjuvant...

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Section: Conclusion -In Women Withmentioning

confidence: 99%

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

2007

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“…Although the use of metformin (N,N 0 -dimethylbiguanide) is becoming accepted and widespread, it has been clinically used without a complete understanding of the mechanisms involved. Metformin reduces insulin resistance (Fedorcsak et al 2003, Harbone et al 2003, Lord et al 2003, affects ovarian steroidogenesis (La Marca et al 2002, Mansfield et al 2003, Tosca et al 2006a, and restores ovulation of anovulatory women with PCOS (Palomba et al 2004(Palomba et al , 2006. The treatment with metformin is also able to improve uterine vascularization in PCOS patients (Palomba et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of DHEA and metformin on corpus luteum in mice

Sander¹,

Facorro²,

Piehl³

et al. 2009

Reproduction

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We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9G1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mare's serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E 2 ) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E 2 and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F 2a (PGF 2a ) or PGE by ovaries with functional CL, whereas DHEA decreased PGF 2a and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E 2 levels from mice with ovaries with functional CL and serum P, PGF 2a and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E 2 levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/ % OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.

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“…PCOS is a heterogeneous disorder, characterised by hyperandrogenism, chronic anovulation and infertility [2][3][4][5]. A significant proportion of PCOS women suffer from insulin resistance, which appears to play a role in the aetiology of PCOS, since amelioration of insulin resistance by lifestyle or pharmacological intervention has been shown to improve hyperandrogenism and fertility [6][7][8][9]. Furthermore, insulin resistance is proposed to be a major risk factor for the development of type 2 diabetes mellitus and subsequent cardiovascular disease [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling

et al. 2006

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Aims/hypothesis Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. Materials and methods Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value ≥7.8 mmol/l) from those with NGT. Results According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone: follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. Conclusions/interpretation Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

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Metformin or Antiandrogen in the Treatment of Hirsutism in Polycystic Ovary Syndrome

Cited by 174 publications

References 31 publications

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

Effect of DHEA and metformin on corpus luteum in mice

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling

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