Journal of Clinical Endocrinology & Metabolism, Vol 69, 151-157, Copyright © 1989 by Endocrine Society

ARTICLES

The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects

T Spinder, JJ Spijkstra, JG van den Tweel, CW Burger, H van Kessel, PG Hompes and LJ Gooren
Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.

Polycystic ovarian disease (PCOD) is associated with elevated serum LH and (sub)normal FSH levels, while serum androgen levels are often elevated. To clarify the role of androgens in this abnormal pattern of gonadotropin secretion, LH secretion was studied in 1) 9 eugonadal female to male transsexual subjects before and during long term (6 months) testosterone (T) administration (250 mg/2 weeks, im), and 2) in a woman with an androgen-secreting ovarian tumor both before and after surgical removal of the tumor. Finally, we studied the effects of high serum androgen levels on ovarian histology in 3) 26 transsexual subjects after long term (9-36 months) T administration (250 mg/2 weeks, im) to assess whether T-induced ovarian abnormalities are similar to those that occur in women with PCOD. Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 +/- 0.8 (+/- SD) to 40.8 +/- 31.9 nmol/L (P less than 0.01), the mean serum dihydrotestosterone level from 0.6 +/- 0.2 to 3.3 +/- 1.5 nmol/L (P less than 0.02), and the mean serum free T level from 9.5 +/- 5.2 to 149 +/- 46 pmol/L (P less than 0.02). Mean serum estrone and estradiol levels were similar before and during T treatment. The mean serum LH level decreased from 6.3 +/- 2.0 to 2.9 +/- 1.1 U/L (P less than 0.01), and the mean FSH levels decreased from 6.6 +/- 2.0 to 3.7 +/- 2.2 U/L (P less than 0.02). Pulsatile LH secretion before and during T treatment was studied in five subjects. Neither the mean nadir LH interval nor the LH pulse amplitude changed significantly in these five subjects. The serum T level in the woman with the androgen-secreting ovarian tumor was 9.6 nmol/L, and it declined to normal after removal of the tumor. Her mean serum LH and FSH levels, the mean nadir LH interval, and LH pulse amplitude were in the normal range before and after removal of the tumor. Studies of ovarian histopathology in 26 transsexual subjects after long term androgen treatment revealed multiple cystic follicles in 18 subjects (69.2%), diffuse ovarian stromal hyperplasia in 21 subjects (80.8%), collagenization of the tunica albuginea in 25 subjects (96.2%), and luteinization of stromal cells in 7 subjects (26.9%). Findings consistent with criteria for the pathological diagnosis of polycystic ovaries, that is 3 of the 4 findings listed above, were present in 18 of the 26 subjects (69.2%).(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				A. Mueller and L. Gooren Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones Eur. J. Endocrinol., September 1, 2008; 159(3): 197 - 202. [Abstract] [Full Text] [PDF]

				L. J. Gooren, E. J. Giltay, and M. C. Bunck Long-Term Treatment of Transsexuals with Cross-Sex Hormones: Extensive Personal Experience J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 19 - 25. [Abstract] [Full Text] [PDF]

				F. C.A. Santos, R. P. Leite, A. M.G. Custodio, K. P. Carvalho, L. H. Monteiro-Leal, A. B. Santos, R. M. Goes, H. F. Carvalho, and S. R. Taboga Testosterone Stimulates Growth and Secretory Activity of the Female Prostate in the Adult Gerbil (Meriones unguiculatus) Biol Reprod, September 1, 2006; 75(3): 370 - 379. [Abstract] [Full Text] [PDF]

				M. H. Slagter, L. J.G. Gooren, A. Scorilas, C. D. Petraki, and E. P. Diamandis Effects of Long-term Androgen Administration on Breast Tissue of Female-to-Male Transsexuals J. Histochem. Cytochem., August 1, 2006; 54(8): 905 - 910. [Abstract] [Full Text] [PDF]

				N. Massin, I. Cedrin-Durnerin, C. Coussieu, J. Galey-Fontaine, J.P. Wolf, and J.-N. Hugues Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study Hum. Reprod., May 1, 2006; 21(5): 1204 - 1211. [Abstract] [Full Text] [PDF]

				M. C M Bunck, A. W F T Toorians, P. Lips, and L. J G Gooren The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals. Eur. J. Endocrinol., April 1, 2006; 154(4): 569 - 575. [Abstract] [Full Text] [PDF]

				G. T'Sjoen, R. Rubens, P. De Sutter, and L. Gooren Authors' Response: The Endocrine Care of Transsexual People J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 1014 - 1015. [Full Text] [PDF]

				V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]

				C. K. Welt, A. E. Taylor, K. A. Martin, and J. E. Hall Serum Inhibin B in Polycystic Ovary Syndrome: Regulation by Insulin and Luteinizing Hormone J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5559 - 5565. [Abstract] [Full Text] [PDF]

				D. P. Merke, S. R. Bornstein, N. A. Avila, and G. P. Chrousos Future Directions in the Study and Management of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency Ann Intern Med, February 19, 2002; 136(4): 320 - 334. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, S. M. Pincus, M. C. Garcia-Rudaz, M. G. Ropelato, M. E. Escobar, and M. Barontini Disruption of the Joint Synchrony of Luteinizing Hormone, Testosterone, and Androstenedione Secretion in Adolescents with Polycystic Ovarian Syndrome J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 72 - 79. [Abstract] [Full Text]

				C. A. Eagleson, M. B. Gingrich, C. L. Pastor, T. K. Arora, C. M. Burt, W. S. Evans, and J. C. Marshall Polycystic Ovarian Syndrome: Evidence that Flutamide Restores Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4047 - 4052. [Abstract] [Full Text]

				K. Vendola, J. Zhou, J. Wang, and C. A.Bondy Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary Hum. Reprod., September 1, 1999; 14(9): 2328 - 2332. [Abstract] [Full Text] [PDF]

				J. Lado-Abeal, J. Rodriguez-Arnao, J. D. C. Newell-Price, L. A. Perry, A. B. Grossman, G. M. Besser, and P. J. Trainer Menstrual Abnormalities in Women with Cushing's Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3083 - 3088. [Abstract] [Full Text]

				S. J. Weil, K. Vendola, J. Zhou, O. O. Adesanya, J. Wang, J. Okafor, and C. A. Bondy Androgen Receptor Gene Expression in the Primate Ovary: Cellular Localization, Regulation, and Functional Correlations J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2479 - 2485. [Abstract] [Full Text]

				C. L. Pastor, M. L. Griffin-Korf, J. A. Aloi, W. S. Evans, and J. C. Marshall Polycystic Ovary Syndrome: Evidence for Reduced Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 582 - 590. [Abstract] [Full Text]

				J. E. Nestler and D. J. Jakubowicz Decreases in Ovarian Cytochrome P450c17{alpha} Activity and Serum Free Testosterone after Reduction of Insulin Secretion in Polycystic Ovary Syndrome N. Engl. J. Med., August 29, 1996; 335(9): 617 - 623. [Abstract] [Full Text] [PDF]

				E. W. C. M. Van Dam, F. Roelfsema, J. D. Veldhuis, F. M. Helmerhorst, M. Frolich, A. E. Meinders, H. M. J. Krans, and H. Pijl Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E865 - E872. [Abstract] [Full Text] [PDF]