Contemporary medical therapy for polycystic ovary syndrome

Polycystic ovary syndrome is a multi‐system endocrinopathy with long‐term metabolic and cardiovascular health consequences. Patients typically present due to symptoms of irregular menstruation, hair growth, or infertility; however, recent management options are aimed at further treating underlying glucose–insulin abnormalities as well as androgen excess for proactive control of symptoms. By a 2003 international consensus conference, diagnosis is made by two out of three criteria: chronic oligoovulation or anovulation after excluding secondary causes, clinical or biochemical evidence of hyperandrogenism (but not necessarily hirsutism due to inter‐patient variability in hair follicle sensitivity), and radiological evidence of polycystic ovaries. Traditional medical treatment options include oral contraceptive pills, cyclic progestins, ovulation induction, and anti‐androgenic medications (aldosterone antagonist, 5α‐reductase antagonist, and follicle ornithine decarboxylase inhibitor). Recent pharmacotherapies include insulin‐sensitizing medications metformin and two thiazolidinediones (rosiglitazone/Avandia® and pioglitazone/Actos®), a CYP19 aromatase inhibitor (letrozole/Femara®), and statins to potentially lower testosterone levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135338/1/ijgo236.pd

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controled study

OBJECTIVE: To determine the effects of a thiazolidinedione (TZD) agonist of peroxisome proliferator-activated receptor (PPAR)-γ, rosiglitazone, in a baboon model of established endometriosis. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Experimental surgery laboratory at the Institute of Primate Research in Nairobi, Kenya. ANIMAL(S): Endometriosis was induced using intrapelvic injection of eutopic menstrual endometrium in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. INTERVENTION(S): Induction of endometriosis by laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue was extracted from each baboon by curettage and a standard amount of endometrium was then seeded onto several peritoneal sites as previously described. About 34-68 days after the induction of laparoscopy, a pre-treatment laparoscopy (baseline disease assessment) was performed in the baboons to record the extent of endometriotic lesions. The 12 baboons were randomized into 3 groups and treated from the day after the staging laparoscopy for a total duration of 30 days. They received either PBS tablets (n=4, placebo control; placebo tablets once a day by mouth for 30 days), GnRH-antagonists (n=4, active control; Ganirelix acetate 125 μg/day for 30 days) or rosiglitazone (n=4, test drug, 2 mg by mouth each day for 30 days). A 3(rd) and final laparoscopy on day 30 after the start of treatment was performed to record the extent of endometriosis. The type of lesion (typical, red, white and suspicious) was recorded. Biopsies were obtained to confirm the histological presence of endometriosis. MAIN OUTCOME MEASURE(S): A videolaparoscopy was performed 30 days after treatment to document the number and surface area of endometriotic lesions as well as to calculate the revised American Society for Reproductive Medicine score (rAFS) and stage. RESULT(S): The surface area of endometriotic lesions was statistically significantly lower in rosiglitazone treated baboons when compared to the placebo group (P<0.05). Baboons treated with rosiglitazone or Ganirelix had a greater negative relative change in surface area of peritoneal endometriotic lesions than controls (P<0.05). The overall, weighted appearance of the lesion types suggests that rosiglitazone may deter the development of newer endometriotic lesions. CONCLUSION(S): A PPAR-γ ligand, rosiglitazone, can effectively diminish the burden of endometriosis disease in the baboon endometriosis model. This animal model holds promise that a TZD drug may be helpful in women with endometriosis

The role of scientists and clinicians in raising public support for animal research in reproductive biology and medicine

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