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The physical and hormonal characteristics of 60 male-to-female transsexuals and 30 female-to-male transsexuals were measured before or during treatment with commonly used forms and dosages of hormones. Only two patients (both female-to-male) had either a congenital defect in hormonal production or abnormal genital development. Patients were seen at 3- to 6-month intervals for an average of 18 months. The response to therapy was examined over time; physical parameters, hormonal concentrations, liver function tests, lipids, and glucose were measured. Three patients were changed from ethinyl estradiol to conjugated estrogen because of liver enzyme elevations. Ethinyl estradiol (0.1-0.5 mg/day) was equal to conjugated estrogen (7.5-10 mg/day) in its ability to suppress testosterone and gonadotropins and to promote breast growth. Maximum breast growth required 2 years of therapy. During treatment with testosterone, female-to-male transsexuals had a significant mild elevation of cholesterol and triglyceride. The female-to-male transsexuals receiving testosterone cypionate, 200 mg every 2 weeks, ceased to have menstrual periods and became progressively masculinized. A mean maximal clitoral length of 4.6 cm which achieved by 1 year of therapy. Based on the data generated by this study, we recommend as hormonal therapy 0.1-0.5 mg/day of ethinyl estradiol or 7.5-10 mg/day of conjugated estrogen for male-to-female transsexuals, and intramuscular testosterone cypionate, 200 mg every 2 weeks, for female-to-male transsexuals.

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A B S T R A C T Plasma luteinizing hormone (LH) and testosterone (T) were measured by radioimmunoassay in nine pubertal boys and three sexually mature young men at 20-min intervals for 24 h. Plasma LH and T were also measured in one boy during a delayed sleep onset study. Polygraphic monitoring was carried out to identify precisely sleep onset, wakefulness, and specific sleep stages. In all nine pubertal boys the plasma T concentration fluctuated and was significantly higher during normal nocturnal sleep as compared to daytime waking. This increased T secretion during sleep was temporally linked to the characteristic pubertal sleep augmentation of LH secretion. To define further the relationship of this increased T secretion to sleep, plasma LH and T were also measured in three of the pubertal boys after acute (1-day) reversal of the sleepwake cycle. One of these boys was also studied after 3 days of sleep-wake cycle reversal. The results of these studies showed that plasma T was now augmented during the reversed daytime sleep period; the mean T concentrations during this period were significantly higher (P < 0.001) than during nocturnal waking in all four studies. Measurement of plasma LH and T in the three sexually mature young men showed episodic secretion of LH and T during both waking and sleep periods; there was no consistent significant augmentation of LH or T secretion during sleep. This study demonstrates that (a) in normal pubertal boys and sexually mature young men plasma T fluctuates epi-A preliminary portion of this work has been reported as an abstract (1973. J. Clin. Invest. 52: 11a).Received for publication 19 October 1973 and in revised form 26 February 1974. sodically; (b) there is marked augmentation of T secretion during sleep in pubertal boys, which is dependent on increased LH secretion; (c) this pubertal LH-T secretory "program" is dependent on sleep, since it shifts with delayed sleep onset and reversal of the sleep-wake cycle; and (d) this demonstrable tropic effect of LH on T is evident only during puberty, since sexually mature young men fail to show any consistent relationship between LH and T secretion either awake or asleep. INTRODUCTIONRecent use of the combination of plasma sampling at frequent intervals, sensitive and specific radioimmunoassays, and polygraphic recording of sleep has led to a revised perspective of hormone-secretory dynamics. These procedures, employed throughout the complete 24-h sleep-wake cycle, allowed the recognition of the episodic secretion of cortisol (1-3), ACTH (4, 5). luteinizing hormone (LH)1 (6-13) and follicle-stimulating hormone (FSH) (8,11,12) in adult men and women. The polygraphic monitoring of sleep showed the important role of sleep in the secretion of human growth hormone (14-17), human prolactin (18-20), LH and FSH in normal pubertal girls (21-24), and LH in pubertal boys (22,23).