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The Oral Administration of Methyl Testosterone in a Male Castrate
THE ORAL ADMINISTRATION OF METHYL TESTOSTERONE IN A MALE CASTRATE RITA S. FINKLER
AND
GEORGE M. COHN
From the Deparl'ment of Endocrinology of the Newark Beth Israel Hospital, Newark, N. J.
Synthetic male sex hormones (testosterone propionate and acetate) are being used extensively in the treatment of pre-pubertal eunuchs, male castrates, eunuchoids and male menopause. These hormones are administered either by the intramuscular route or by implantation of pellets. Though the value of this therapy has been well established, the need for frequent visits to the doctor's office for injections constitutes a definite barrier to its more extensive use, while pellet implantation on the other hand is not suitable in the majority of patients. Since the chief effect of androgens is substitutional, a fairly continuous and prolonged course of treatment is usually necessary. Therefore, orally potent androgens are a welcome addition to this form of therapy. Heretofore, androgens prepared for oral use did not appear to have any appreciable potency, but recently a new compound, methyl testosterone, was synthesized by Ruzicka et al. The potency by oral administration of this preparation was established on castrated rats by Miescher and Tschopp. The product is issued in tablets containing 10 and 25 mg. of active substance. Few reports concerning the clinical application of methyl testosterone have appeared in the medical literature. Foss reports its successful use in a post-pubertal eunuch and in 2 cases of hypogonadism. McCullagh reports the successful use of oral methyl testosterone in eunuchoidism, and Kearns in testicular deficiency. We have used methyl testosterone tablets (Oreton M) 1 in 12 cases of hypogonadism, male climacteric, impotence and in 1 case of a male castrate. In the latter case the effect was so striking that a report of the case in detail follows. Case report. E. P., a single white male, aged 38, was admitted to the Endocrine Clinic on May 16, 1940. He complained cif severe frontal headaches, crying spells, gain in weight, despondency and absence of libido. All these 1 Methyl testosterone (oreton M) and testosterone propionate (Oreton) were supplied through the courtesy of Dr. Max Gilbert of the Schering Corporation of Bloomfield, N. J. 548
METHYL TESTOSTERONE IN MALE CASTRATE
549
symptoms had been developing gradually over a period of years, but during the last 2 months had become very severe, resulting in mental depression. The past history was irrelevant except for tuberculosis of the right knee for which an ankylosing operation had been performed about 20 years ago. Shortly afterwards a tuberculous infection of both testes developed following trauma, and necessitated their surgical removal. The right testicle was removed in 1920, and the left in 1922; there followed a gradual loss of libido
FrG. l. (left) Before therapy; (right) after therapy
lous with the areolae about the nipples wider than found in the male. The abdomen had an apron-like pad of fat; the right leg was stiff at the knee and was six inches shorter than the left. A built-up shoe compensated for the shortening. The axillary hair was sparse, the pubic hair feminine in distribution; the scrotum rugate, but without testes and the penis, hidden by the pubic fat, appeared to be of the develop;Lent found in a 13 year old boy, The however, preserved its low masculine pitch. Laboratory findings: Wassermann and Kahn reactions negative; urinalysis negative; basal metabolism rate minus 14 per cent. X-ray: Sella turcica somewhat small with union of the anterior and posterior clinoid processes; no evidence of bone destruction.
550
RITA S. FINKLER AND GEORGE M. COHN
On May 21, 1940 the patient was placed on a reducing diet and intramuscular injections of testosterone propionate (Oreton) 1 25 mg. three times a week. After the administration of a total of 100 mg. of testosterone propionate, spontaneous erections began to occur, each lasting about 20 minutes. The intensity and frequency of the headaches gradually decreased, and the patient became emotionally stable. On June 15, the patient reported increased libido and 3 to 4 strong erections per day, particularly on the day of injection. The increase in libido, however, became so great that the urge was rather annoying to the patient. The dose was then decreased to 10 mg. twice weekly, but the frequent erections still persisted. On June 20, because of the discomfort caused by the persistent erections, testosterone propionate was discontinued and oral medication with 25 mg. tablets of methyl testosterone daily was initiated. On June 27, the patient reported the loss of libido and erections, the recurrence of headaches and marked restlessness. The amount of methyl testosterone was then increased to 75 mg. daily in divided doses. On July 11, the patient reported that he felt better than he had in the last few years; the headaches had disappeared and there was a sense of general well-being. Erections occurred about 1 hour after taking a tablet of 25 mg. of methyl testosterone. The previous symptoms recurred each time an attempt was made to reduce the daily dose. The patient reported that 3 tablets of 25 mg. each, taken about 6 hours apart, carried him smoothly throughout the day. When the ingestion of a tablet was delayed, "the ears would become hot and the severe 'headaches would come on suddenly." Relief was noted about one-half hour after the tablet was taken. On August 12, the patient reported that he felt well and cheerful, had no headaches or nervous tension and erections were not excessive or annoying. On August 28, the patient reported complete absence of all previous annoying symptoms, and continuation of a smooth response to therapy. There had been a loss of 31 pounds in weight, and an increase in the size of the penis and scrotum (:fig. 1). A metabolic test repeated in September was plus 6 per cent. This elevation in the metabolic rate occurred in spite of the drop usually seen when there is an appreciably lose in weight and is in keeping with the :findings of others who have used methyl testosterone. SUMMARY
A report is presented comparing the effects of intramuscular and oral use of androgens in a male castrate. The oral administration of methyl testosterone gave the patient a smooth and well sustained relief from symptoms, as compared with the uneven response to intramuscular injections.
METHYL TESTOSTERONE IN MALE CASTRATE
CONCLUSIONS
Oral therapy with methyl testosterone in a maJe castrate proved to be adequate for the control of the following symptoms: headaches, spells, gain in weight, despondency and loss of libido. External genitalia increased in size and the metabolic rate rose frmn minus 14 per cent to plus 6 per cent. REFERENCES Foss, G. L.: Brit. M. J., 2: 11, 1939. KEARNS, W. M ... J. Clinical Endocrinology, 1: 126, 1941. McCuLLAGH, E. P . Cleveland Clinic QuarL, 7: 226, 1940. TvirnsctIER, K., AND TSCHOPP, E.: Schweiz. med. vVchnschr.. 68: 1258, 1938. RUZJCKA, L., GOLDBERG, M. w., AND MEYER, J.. HelveL chim. acta., 18: 994, 1935. ----, GOLDBERG, M. W., AND ROSENBERG, H. R.: Helvet. chim. acta., 18: 1487, 1935.
AND
GEORGE M. COHN
From the Deparl'ment of Endocrinology of the Newark Beth Israel Hospital, Newark, N. J.
Synthetic male sex hormones (testosterone propionate and acetate) are being used extensively in the treatment of pre-pubertal eunuchs, male castrates, eunuchoids and male menopause. These hormones are administered either by the intramuscular route or by implantation of pellets. Though the value of this therapy has been well established, the need for frequent visits to the doctor's office for injections constitutes a definite barrier to its more extensive use, while pellet implantation on the other hand is not suitable in the majority of patients. Since the chief effect of androgens is substitutional, a fairly continuous and prolonged course of treatment is usually necessary. Therefore, orally potent androgens are a welcome addition to this form of therapy. Heretofore, androgens prepared for oral use did not appear to have any appreciable potency, but recently a new compound, methyl testosterone, was synthesized by Ruzicka et al. The potency by oral administration of this preparation was established on castrated rats by Miescher and Tschopp. The product is issued in tablets containing 10 and 25 mg. of active substance. Few reports concerning the clinical application of methyl testosterone have appeared in the medical literature. Foss reports its successful use in a post-pubertal eunuch and in 2 cases of hypogonadism. McCullagh reports the successful use of oral methyl testosterone in eunuchoidism, and Kearns in testicular deficiency. We have used methyl testosterone tablets (Oreton M) 1 in 12 cases of hypogonadism, male climacteric, impotence and in 1 case of a male castrate. In the latter case the effect was so striking that a report of the case in detail follows. Case report. E. P., a single white male, aged 38, was admitted to the Endocrine Clinic on May 16, 1940. He complained cif severe frontal headaches, crying spells, gain in weight, despondency and absence of libido. All these 1 Methyl testosterone (oreton M) and testosterone propionate (Oreton) were supplied through the courtesy of Dr. Max Gilbert of the Schering Corporation of Bloomfield, N. J. 548
METHYL TESTOSTERONE IN MALE CASTRATE
549
symptoms had been developing gradually over a period of years, but during the last 2 months had become very severe, resulting in mental depression. The past history was irrelevant except for tuberculosis of the right knee for which an ankylosing operation had been performed about 20 years ago. Shortly afterwards a tuberculous infection of both testes developed following trauma, and necessitated their surgical removal. The right testicle was removed in 1920, and the left in 1922; there followed a gradual loss of libido
FrG. l. (left) Before therapy; (right) after therapy
lous with the areolae about the nipples wider than found in the male. The abdomen had an apron-like pad of fat; the right leg was stiff at the knee and was six inches shorter than the left. A built-up shoe compensated for the shortening. The axillary hair was sparse, the pubic hair feminine in distribution; the scrotum rugate, but without testes and the penis, hidden by the pubic fat, appeared to be of the develop;Lent found in a 13 year old boy, The however, preserved its low masculine pitch. Laboratory findings: Wassermann and Kahn reactions negative; urinalysis negative; basal metabolism rate minus 14 per cent. X-ray: Sella turcica somewhat small with union of the anterior and posterior clinoid processes; no evidence of bone destruction.
550
RITA S. FINKLER AND GEORGE M. COHN
On May 21, 1940 the patient was placed on a reducing diet and intramuscular injections of testosterone propionate (Oreton) 1 25 mg. three times a week. After the administration of a total of 100 mg. of testosterone propionate, spontaneous erections began to occur, each lasting about 20 minutes. The intensity and frequency of the headaches gradually decreased, and the patient became emotionally stable. On June 15, the patient reported increased libido and 3 to 4 strong erections per day, particularly on the day of injection. The increase in libido, however, became so great that the urge was rather annoying to the patient. The dose was then decreased to 10 mg. twice weekly, but the frequent erections still persisted. On June 20, because of the discomfort caused by the persistent erections, testosterone propionate was discontinued and oral medication with 25 mg. tablets of methyl testosterone daily was initiated. On June 27, the patient reported the loss of libido and erections, the recurrence of headaches and marked restlessness. The amount of methyl testosterone was then increased to 75 mg. daily in divided doses. On July 11, the patient reported that he felt better than he had in the last few years; the headaches had disappeared and there was a sense of general well-being. Erections occurred about 1 hour after taking a tablet of 25 mg. of methyl testosterone. The previous symptoms recurred each time an attempt was made to reduce the daily dose. The patient reported that 3 tablets of 25 mg. each, taken about 6 hours apart, carried him smoothly throughout the day. When the ingestion of a tablet was delayed, "the ears would become hot and the severe 'headaches would come on suddenly." Relief was noted about one-half hour after the tablet was taken. On August 12, the patient reported that he felt well and cheerful, had no headaches or nervous tension and erections were not excessive or annoying. On August 28, the patient reported complete absence of all previous annoying symptoms, and continuation of a smooth response to therapy. There had been a loss of 31 pounds in weight, and an increase in the size of the penis and scrotum (:fig. 1). A metabolic test repeated in September was plus 6 per cent. This elevation in the metabolic rate occurred in spite of the drop usually seen when there is an appreciably lose in weight and is in keeping with the :findings of others who have used methyl testosterone. SUMMARY
A report is presented comparing the effects of intramuscular and oral use of androgens in a male castrate. The oral administration of methyl testosterone gave the patient a smooth and well sustained relief from symptoms, as compared with the uneven response to intramuscular injections.
METHYL TESTOSTERONE IN MALE CASTRATE
CONCLUSIONS
Oral therapy with methyl testosterone in a maJe castrate proved to be adequate for the control of the following symptoms: headaches, spells, gain in weight, despondency and loss of libido. External genitalia increased in size and the metabolic rate rose frmn minus 14 per cent to plus 6 per cent. REFERENCES Foss, G. L.: Brit. M. J., 2: 11, 1939. KEARNS, W. M ... J. Clinical Endocrinology, 1: 126, 1941. McCuLLAGH, E. P . Cleveland Clinic QuarL, 7: 226, 1940. TvirnsctIER, K., AND TSCHOPP, E.: Schweiz. med. vVchnschr.. 68: 1258, 1938. RUZJCKA, L., GOLDBERG, M. w., AND MEYER, J.. HelveL chim. acta., 18: 994, 1935. ----, GOLDBERG, M. W., AND ROSENBERG, H. R.: Helvet. chim. acta., 18: 1487, 1935.