Thiazolidenediones (TZDs) have also been examined for their possible role in the treatment of infertility in PCOS. The main mechanism of action is through activation of the nuclear peroxisome proliferator-activated receptor gamma (PPAR-g), which decreases peripheral insulin resistance (73, 74). Troglitazone was the first drug of this class that was shown to improve ovulation rates, hyperandrogenemia and insulin resistance compared with placebo (75). It has been shown in vitro to impede LH and insulin stimulation of ovarian androgen production as thecal cells also possess PPAR-g receptors (76). Troglitazone has since been withdrawn from the market due to concerns of hepatotoxicity.
Two of the newer TZDs, rosiglitazone and pioglitazone, have also demonstrated improved reproductive function in women with PCOS. A prospective study by Belli et al. examining the effects of rosiglitazone showed improved menstrual regularity and decreased insulin resistance (77). A randomized, controlled, double-blind trial by Baillargeon et al. showed increased ovulatory frequency and reduced hyperandrogenemia following treatment with rosiglitazone in nonobese patients with normal insulin sensitivity (78). A recent randomized controlled trial found adding rosiglitazone to clomiphene to be more effective in ovulation induction than adding metformin in clomiphene-resistant PCOS (79).
In a randomized, double-blind, controlled trial, Brettenthaler et al. showed significantly improved insulin sensitivity, hyperandrogenism and ovulation rates during treatment with pioglitazone (80). When pioglitazone was added in a small sample of patients nonresponsive to metformin, patients were found to have improved menstrual regularity and decreased insulin resistance (81). TZDs are a category C medication, which has limited their clinical use in the treatment of infertility. Larger randomized con trolled trials are needed to determine the utility and safety of TZDs in the treatment of anovulatory infertility in PCOS.
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