Abstract 1326: Oral enclomiphene citrate lowers IGF-1 in men with secondary hypogonadism while raising testosterone: Implications for cancer prevention.

Abstract

Abstract Introduction: Lowered hGH and IGF-1 have been linked with protection from various cancers. Methods and Subjects: We determined levels of IGF-1 and pituitary hormones in men with secondary hypogonadism under treatment with enclomiphene (a.k.a. Androxal) in comparison to topical testosterone (T) or placebo. Three, randomized, blinded, phase II studies evaluating daily oral Androxal were performed: ZA-201 investigated 12 men taking 25mg of Androxal in comparison to a gel for 6 months, ZA-202 enrolled 119 diabetic men taking 12.5 or 25 mg Androxal versus placebo for 3 months, and ZA-204 investigated 47 men taking 6.25mg, 12.5mg and 25mg Androxal versus another gel for 6 weeks. All subjects had initial total T <350 ng/dL and low-to-normal LH (<12 IU/L). Serum samples were taken for T, LH and FSH before and after dosing. We could not measure hGH directly but measured its marker, liver-produced IGF-1. Results: All treatments raised T into the normal range (300-1000 ng/dL), but placebo did not in ZA-202. Androxal elevated LH and FSH. Gels decreased LH and FSH strongly. Unexpected was the strong action of Androxal to lower serum IGF-1 in all three trials. Both Androxal and topicals lowered serum IGF-1 but Androxal was more effective. An example is given from ZA-204 below. Dose groups showed no differences in IGF-1 before (p = 0.94) but significance after treatment (p = 0.03), Conclusions: Endocrine profile indicate that enclomiphene citrate stimulates the pituitary, resulting in increased LH and FSH and eventually T. The results on IGF-1 cannot be attributed to T since topicals, when used, raised T but not IGF-1 whereas only enclomiphene citrate raised T but lowered IGF-1. Enclomiphene citrate is different from topicals and may be a new way to relieve low T in men with an intact hypothalamus-pituitary-testicular axis. If Androxal can lower hGH or IGF-1 in aging men at risk for prostate cancer, its use in men with secondary hypogonadism is an important new treatment. Effect of Treatment on IGF-1 dose subjects IGF-1 (SD)before IGF-1 (SD) after Versus Gel MMW 6.25mg 12 101 (43) 54 (30) p<0.01 12.5mg 10 94 (47) 50 (24) p<0.005 25mg 12 96 (45) 62 (42) p<0.01 Gel 13 103 (46) 90 (34) Citation Format: Ronald D. Wiehle, Gregory K. Fontenot. Oral enclomiphene citrate lowers IGF-1 in men with secondary hypogonadism while raising testosterone: Implications for cancer prevention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1326. doi:10.1158/1538-7445.AM2013-1326