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      Association of insulin resistance with hyperandrogenia in women.

      1 , ,
      Hormone research
      S. Karger AG

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          Abstract

          In humans, the skin is a target tissue for androgen action; hair growth and sebum secretion are under active androgen control. An increased production or metabolism of testosterone, the main active androgen, shows up clinically in dermatological symptoms such as hirsutism, hyperseborrheic acne and alopecia. Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarian function. PCOS patients have amenorrhea or severe oligomenorrhea, increased testosterone levels and most often enlarged polycystic ovaries on ultrasound examination. In addition, many PCOS patients have a tendency to accumulate abdominal fat and/or to develop obesity. Some also display a particular metabolic pattern including an atherogenic lipid profile, glucose intolerance and an increased fasting insulin level, which is known to be closely linked with an insulin resistant state. Several studies have now reported that PCOS patients show increased incidence of type 2 diabetes and cardiovascular disease. In addition to being a target for androgens the skin has abundant insulin receptors on the keratinocyte surface membrane and acanthosis nigricans is a common symptom of severe insulin resistance among patients with insulin receptor disorders. However, acanthosis nigricans could also be present in PCOS women given evidence of the intensity of their insulin resistance. This presentation will review the mutual relationship between hyperandrogenia and insulin resistance, with particular attention paid to: (1) insulin secretion and insulin sensitivity in PCOS; (2) the complexity of the molecular mechanisms involved in insulin resistance; (3) the paradoxical relationship between insulin resistance and hyperandrogenia; (4) the current genetic studies; and (5) new avenues for long-term treatment of PCOS women.

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          Most cited references7

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          Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome.

          Our preliminary family studies have suggested that some female first-degree relatives of women with polycystic ovary syndrome (PCOS) have hyperandrogenemia per se. It was our hypothesis that this may be a genetic trait and thus could represent a phenotype suitable for linkage analysis. To investigate this hypothesis, we examined 115 sisters of 80 probands with PCOS from unrelated families. PCOS was diagnosed by the combination of elevated serum androgen levels and
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            Signaling mechanisms that regulate glucose transport.

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              Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.

              Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene. We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome. Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo. Serum progesterone was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on any of these days. Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study. Among the 21 women given metformin plus clomiphene, the mean (+/-SE) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute (40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute, P=0.03), but it did not change significantly in the 25 women given placebo plus clomiphene. Nineteen of the 21 women (90 percent) who received metformin plus clomiphene ovulated (mean peak serum progesterone concentration, 23.8+/-3.4 ng per milliliter [7.6+/-10.9 nmol per liter]). Two of the 25 women (8 percent) who received placebo plus clomiphene ovulated (P<0.001). Overall, 31 of the 35 women (89 percent) treated with metformin ovulated spontaneously or in response to clomiphene, as compared with 3 of the 26 women (12 percent) treated with placebo. The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin.
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                Author and article information

                Journal
                Horm. Res.
                Hormone research
                S. Karger AG
                0301-0163
                0301-0163
                2000
                : 54
                : 5-6
                Affiliations
                [1 ] Fédération d'Endocrinologie de l'Hôpital de l'Antiquaille, Hospices Civils de Lyon, and INSERM U329, Lyon, France. michel.pugeat@chu-lyon.fr
                Article
                53281
                10.1159/000053281
                11595827
                0658720f-be57-4276-9311-42ba635e3d08
                History

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