Very low dose spironolactone protects experimentally-induced polycystic ovarian syndrome from insulin-resistant metabolic disturbances by suppressing elevated circulating testosterone.
Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age and hyperandrogenism is a prominent feature of PCOS resulting in infertility and increased risk of developing metabolic disorders including insulin resistance (IR), abdominal adiposity, glucose intolerance and cardiovascular diseases. Spironolactone (SPL), a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. In this study, we investigated the effects of SPL on IR and metabolic disturbances in letrozole-induced PCOS rats. Eighteen adults female Wistar rats were randomly divided into 3 groups and treated with vehicle, letrozole (LET; 1 mg/kg) and LET + SPL (SPL; 0.25 mg/kg), p.o. once daily for 21 consecutive days. Results showed that LET treatment induced PCOS characterised by elevated plasma testosterone and luteinizing hormone (LH) accompanied with increased body weight and visceral adiposity, IR, glucose intolerance, dyslipidemia and altered histomorphological ovaries. Treatment with SPL however attenuated the elevated testosterone in LET-induced PCOS model accompanied with a reversal in all the observed alterations. Taken together, analysis of the physical, biochemical and histological evidences shows that the protective effect of this very low dose spironolactone may be through its anti-androgenic mechanism.
['Adeyanju|Oluwaseun A|OA|', 'Falodun|Timothy O|TO|', 'Fabunmi|Oyesanmi A|OA|', 'Olatunji|Lawrence A|LA|', 'Soladoye|Ayodele O|AO|']
D000726:Androgen Antagonists D000818:Animals D005260:Female D007333:Insulin Resistance D000077289:Letrozole D007986:Luteinizing Hormone D000451:Mineralocorticoid Receptor Antagonists D011085:Polycystic Ovary Syndrome D051381:Rats D017208:Rats, Wistar D013148:Spironolactone D013739:Testosterone
Spironolactone Testosterone PCOS Infertility Insulin resistance