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Further Observations on the Rebound Phenomenon in the Treatment of Certain Types of Spermatogenic Dysfunction
'THE JOURNAL OF UROLOGY
Vol. 75, No. 6, June 1956
Printed in U.S.A.
Fl'RTHER OBSERVATIONS ON THE REBOUND PHENOMENON IN THE TREATMENT OF CERTAIN TYPES OF SPERMATOGENIC DYSFUNCTION JAMES H. McDONALD
AND
NORRIS J. HECKEL
Frum the Department of Urology, Presbyterian Hospital of Chicago in affiliation with the University of Illinois Colle(le of iviedicine, Chicago, Ill.
In 1951 a report was made on the increase in the number of spermatozoa in oligospermic men following the use of testosterone propionate. 1 In some of these patients a comparison of testicular biopsies taken prior to treatment with biopsies taken after treatment revealed a definite improvement in the spermatogenic activity. This observation, on testicular biopsies, confirmed a previous report by Heller and Nelson 2 who made an extensive histological study of testicular biopsies in apparently normal men who were given testosterone and found an improvement in testicular morphology and function. During the past several years we have been interested in a more specific criterion for the selection of patients for treatment, and have included a review of a group of oligospermic men treated with testosterone propionate. A total of 116 oligospermic patients who were physically normal and without evidence of endocrine disease have been treated. Testosterone propionate 50 mg. was given intramuscularly 3 times a ·week, or 200 mg. testosterone cyclopentylpropionate intramuscularly once a week. Pretreatment testicular biopsies were secured in a majority of these patients. A 50 million increase in total spermatozoa was arbitrarily selected as indicative of a "rebound phenomenon." Some patients had substantial increases but did not reach the required 50 million increase to qualify as a "rebound." Insufficient evidence was available for classification of 32 of these patients. Seventy-three patients have been followed sufficiently to allow definite conclusions to be made. Of these, 28 patients (:38 per cent) secured a spermatogenic rebound with total spermatozoa far exceeding their pretreatment level and in all instances an increase of at least 50 million over the pretreatment counts. Four of these patients receded to pretreatment levels in from five months to two years. Forty-five patients did not secure a rebound. However, 13 of these had an increase of 13 to 46 million in the total spermatozoa counts, with an average increase of 32 million. In a revimv of the testicular biopsies of these patients, 11 had marked germinal cell atrophy, ;3 had severe regional fibrosis, and 9 patients had no biopsies. None of these patients should have received treatment because of the inability of the germinal epithelium to respond or because of the unknown quantity in the absence of biopsy. Read at annual meeting, North Central Section of American Urological Association, Chicago, Ill. September 29-October 1, 1955. 1 Heckel, N. J., Rosso, W. A. and Kestel, L.: J. Clin. Endocrinol., 11: 235-245, 195L 2 Heller, C. G., Nelson, W. 0., Hill, I. B., Henderson, E., Maddock, W. 0., Jungck, E. C., Paulsen, C. A. and Mortimore, G. E.: Fertility and Sterility, 1: 415-422, 1950. 990
F1u. 1. A, testicular biopsy of oligospermic man showing disorganization of spermatogenesis and sloughing of immature cells. B, testicular biopsy ,bowing incomplete germinal o,ll arrest predominate],· a( pr:mar,· spermatocyte level.
F1 G. 2. A, testicu Jar biopsy showing germinal cell atrophy. B, testicular biopsy showing extensive regional pcritulmlar fibrosis.
991
992
J. H. McDONALD AND N. J. HECKEL
Eleven patients were originally azoospermic, and the condition was not altered by treatment. In the 28 patients who exhibited the "rebound phenomenon," 20 pregnancies have been produced, resulting in 13 normal babies, 2 miscarriages, and one ectopic pregnancy. Following our reports in 1951 and 1952,3 • 4 there was considerable skepticism as to the validity of this work. However, the work of Charny and Heller give additional evidence that a "rebound phenomenon" can be secured in carefully selected and properly treated oligospermic men. The most important criterion for the effective treatment with testosterone propionate is the testicular morphology as determined by the pretreatment biopsy. At the present time we believe that this treatment is indicated in the men who are oligospermic, physically normal, and the testicular biopsy reveals changes of 1) disorganization of spermatogenesis with sloughing of immature cells (fig. 1, A), and 2) incomplete germinal cell arrest (fig. 1, B). Efforts to secure improvement in patients whose testicular biopsy revealed germinal cell atrophy (fig. 2, A) or extensive areas of regional fibrosis (fig. 2, B) have been disappointing. Charny recently reported that treatment with testosterone propionate has produced spermatozoa in the ejaculate of a previously azoospermic man. 5 CONCLUSIONS
Testosterone propionate is indicated in the treatment of patients who have an oligospermia when the testicular biopsy reveals a) disorganized spermatogenesis, or b) incomplete germinal cell arrest. Testicular morphology is the most important criterion in determining the indication for treatment. Twenty eight of 73 oligospermic men had a rebound in spermatogenesis exceeding 50 million in the total spermatozoa count. Following treatment, these patients have produced a total of 20 pregnancies in their wives.
122 S. Michigan Ave., Chicago 3, Ill. • Heckel, N. J. and McDonald, J. H.: Fertility and Sterility, 3: 49-61, 1952. 4 Heckel, N. J. and McDonald, J. H.: N. Y. Acad. Sc., 55: 725-733, 1952. 5 Charny, C. W.: Paper read at the Section of Urology, American Medical Association annual meeting, Atlantic City, N. J. June 1955.
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Vol. 75, No. 6, June 1956
Printed in U.S.A.
Fl'RTHER OBSERVATIONS ON THE REBOUND PHENOMENON IN THE TREATMENT OF CERTAIN TYPES OF SPERMATOGENIC DYSFUNCTION JAMES H. McDONALD
AND
NORRIS J. HECKEL
Frum the Department of Urology, Presbyterian Hospital of Chicago in affiliation with the University of Illinois Colle(le of iviedicine, Chicago, Ill.
In 1951 a report was made on the increase in the number of spermatozoa in oligospermic men following the use of testosterone propionate. 1 In some of these patients a comparison of testicular biopsies taken prior to treatment with biopsies taken after treatment revealed a definite improvement in the spermatogenic activity. This observation, on testicular biopsies, confirmed a previous report by Heller and Nelson 2 who made an extensive histological study of testicular biopsies in apparently normal men who were given testosterone and found an improvement in testicular morphology and function. During the past several years we have been interested in a more specific criterion for the selection of patients for treatment, and have included a review of a group of oligospermic men treated with testosterone propionate. A total of 116 oligospermic patients who were physically normal and without evidence of endocrine disease have been treated. Testosterone propionate 50 mg. was given intramuscularly 3 times a ·week, or 200 mg. testosterone cyclopentylpropionate intramuscularly once a week. Pretreatment testicular biopsies were secured in a majority of these patients. A 50 million increase in total spermatozoa was arbitrarily selected as indicative of a "rebound phenomenon." Some patients had substantial increases but did not reach the required 50 million increase to qualify as a "rebound." Insufficient evidence was available for classification of 32 of these patients. Seventy-three patients have been followed sufficiently to allow definite conclusions to be made. Of these, 28 patients (:38 per cent) secured a spermatogenic rebound with total spermatozoa far exceeding their pretreatment level and in all instances an increase of at least 50 million over the pretreatment counts. Four of these patients receded to pretreatment levels in from five months to two years. Forty-five patients did not secure a rebound. However, 13 of these had an increase of 13 to 46 million in the total spermatozoa counts, with an average increase of 32 million. In a revimv of the testicular biopsies of these patients, 11 had marked germinal cell atrophy, ;3 had severe regional fibrosis, and 9 patients had no biopsies. None of these patients should have received treatment because of the inability of the germinal epithelium to respond or because of the unknown quantity in the absence of biopsy. Read at annual meeting, North Central Section of American Urological Association, Chicago, Ill. September 29-October 1, 1955. 1 Heckel, N. J., Rosso, W. A. and Kestel, L.: J. Clin. Endocrinol., 11: 235-245, 195L 2 Heller, C. G., Nelson, W. 0., Hill, I. B., Henderson, E., Maddock, W. 0., Jungck, E. C., Paulsen, C. A. and Mortimore, G. E.: Fertility and Sterility, 1: 415-422, 1950. 990
F1u. 1. A, testicular biopsy of oligospermic man showing disorganization of spermatogenesis and sloughing of immature cells. B, testicular biopsy ,bowing incomplete germinal o,ll arrest predominate],· a( pr:mar,· spermatocyte level.
F1 G. 2. A, testicu Jar biopsy showing germinal cell atrophy. B, testicular biopsy showing extensive regional pcritulmlar fibrosis.
991
992
J. H. McDONALD AND N. J. HECKEL
Eleven patients were originally azoospermic, and the condition was not altered by treatment. In the 28 patients who exhibited the "rebound phenomenon," 20 pregnancies have been produced, resulting in 13 normal babies, 2 miscarriages, and one ectopic pregnancy. Following our reports in 1951 and 1952,3 • 4 there was considerable skepticism as to the validity of this work. However, the work of Charny and Heller give additional evidence that a "rebound phenomenon" can be secured in carefully selected and properly treated oligospermic men. The most important criterion for the effective treatment with testosterone propionate is the testicular morphology as determined by the pretreatment biopsy. At the present time we believe that this treatment is indicated in the men who are oligospermic, physically normal, and the testicular biopsy reveals changes of 1) disorganization of spermatogenesis with sloughing of immature cells (fig. 1, A), and 2) incomplete germinal cell arrest (fig. 1, B). Efforts to secure improvement in patients whose testicular biopsy revealed germinal cell atrophy (fig. 2, A) or extensive areas of regional fibrosis (fig. 2, B) have been disappointing. Charny recently reported that treatment with testosterone propionate has produced spermatozoa in the ejaculate of a previously azoospermic man. 5 CONCLUSIONS
Testosterone propionate is indicated in the treatment of patients who have an oligospermia when the testicular biopsy reveals a) disorganized spermatogenesis, or b) incomplete germinal cell arrest. Testicular morphology is the most important criterion in determining the indication for treatment. Twenty eight of 73 oligospermic men had a rebound in spermatogenesis exceeding 50 million in the total spermatozoa count. Following treatment, these patients have produced a total of 20 pregnancies in their wives.
122 S. Michigan Ave., Chicago 3, Ill. • Heckel, N. J. and McDonald, J. H.: Fertility and Sterility, 3: 49-61, 1952. 4 Heckel, N. J. and McDonald, J. H.: N. Y. Acad. Sc., 55: 725-733, 1952. 5 Charny, C. W.: Paper read at the Section of Urology, American Medical Association annual meeting, Atlantic City, N. J. June 1955.
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