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Cognitive Effects of Short-Term Manipulation of Serum Sex Steroids in Healthy Young Men

Departments of Psychiatry and Behavioral Sciences (M.M.C., S.C.) and Medicine (B.D.A., K.L.H., J.K.A., W.J.B.), University of Washington School of Medicine, Seattle, Washington 98195; and Geriatric Research (M.M.C.), Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108

Address all correspondence and requests for reprints to: Dr. Monique M. Cherrier, Department of Psychiatry, Box 356560, University of Washington Medical School, 1959 NE Pacific, Seattle, Washingon 98195. E-mail: . cherrier{at}u.washington.edu

Abstract

We examined the effects of sex steroids on cognitive functioning by exogenously manipulating circulating T levels in a group of healthy young men. Thirty-two men were randomized to receive 8 wk of treatment including: 1) im T enanthate 100 mg/wk plus daily oral placebo (T); 2) im placebo/wk plus 125 µg daily oral levonorgestrel (LNG); 3) im T enanthate 100 mg/wk plus 125 µg daily oral LNG (T + LNG); 4) im placebo/wk plus daily oral placebo. Cognitive functions were assessed at baseline and twice during treatment. Serum T and E2 levels were significantly increased in the T and T + LNG groups compared with baseline (P < 0.01) and T levels were significantly decreased in the LNG group (P < 0.05). Verbal memory significantly decreased in the LNG group (P < 0.01) and was maintained by coadministration of T in the T + LNG group. Divided attention was unaffected in the LNG group but improved significantly in the T + LNG group. In summary, decreased serum T levels induced by LNG or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men. These results suggest that short-term changes in sex steroid levels have effects on cognitive function in healthy young men.

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