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FERTIUTY AND STERIUTY
Vol. 32, No.1, July 1979 Printed in U.s A.
Copyright" 1979 The American Fertility Society
THE ROLE OF ANTIANDROGENICACTION IN CYPROTERONE ACETATE-INDUCED MORPHOLOGIC AND BIOCHEMICAL CHANGES IN HUMAN SEMEN
SOMNATH ROY, M.B.B.S., PH.D.* SUDHA CHATTERJEE, M.Sc., PH.D. Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, New Delhi 110016, India
Following the daily administration of 10 mg of cyproterone acetate to three normal fertile human volunteers for 12 to 16 weeks, there was a marked decrease in the count ~otility, and cervical mucus-penetrating ability of spermatozoa, with a concomitant ' mcrease in abnormal and immature forms. The levels of seminal acid phosphatase and glycerylphosphoryl choline were also significantly decreased. Subsequently, concurrer:t daily administration of 75 mg of mesterolone increased the count, motility, and cervzcal mucus-penetrating ability of spermatozoa and stimulated the seminal biochemical constituents. The results indicate that the effects of a low dose of cyproterone acetate are due mainly to peripheral androgen deprivation. Fertil Steril 32:93, 1979
High doses (100 to 200 mg daily) of cyproterone acetate (1 ,2a-methylene-6-chloropregn-4,6-diene17 a-ol-3,20-dione-17 a-acetate), which is a very potent progestogen with a strong antiandrogenic property, inhibits spermatogenesis, libido, and potency in men. 1 It consistently decreases the levels of plasma testosterone, with or without a decrease in the levels offollicle-stimulating hormone (FSH) but no concomitant decrease in the levels of plasma or urinary luteinizing hormone (LH).2 The administration oflow doses (5, 10, and 20 mg daily) of this drug to men causes a decrease in the count and motility of spermatozoa and in thebiochemical constituents of semen with no significant change in libido and potency.2. 3 The blood levels of testosterone are decreased, but the levels of FSH and LH are not altered. 3 Since it has been suggested that the effects of low doses of cyproterone acetate are mainly due to its antiandrogenic action,2 the present investigation was undertaken to determine whether the concurrent administration of androgen could reverse the cyp-
roterone acetate-induced morphologic and biochemical changes in human semen. MATERIALS AND METHODS
Three normal fertile human male volunteers between 32 and 35 years of age were enrolled for the study. The wives of two of them had been tubectomized 2 years earlier. During the control period, three to six semen samples were collected every 2 weeks with 3 days' abstinence prior to each interval, and two blood samples were obtained at 4week intervals. The volunteers received daily 10 mg of cyproterone acetate (CPA) orally, and samples of semen and blood were obtained according to the above schedule. When a marked decrease in the count and motility of the spermatozoa was noted during CPA therapy, daily oral administration of 75 mg of mesterolone, an androgen with little gonadotropin-suppressing action, was started. This combined therapy, which was started at 16, 14, and 12 weeks, respectively, after the initiation of CPA treatment, continued for 7, 12, and 13 weeks, respectively. During this period semen samples were collected at weekly intervals, but the blood samples were obtained at 4-week intervals. General well-being, coital frequency,
Received April 25, 1978; revised March 5, 1979; accepted March 12, 1979. *Professor and Head, Department of Reproductive Biomedicine. To whom reprint requests should be addressed.
93
-----~---~--~----~~'--.........;
94
July 1979
ROY AND CHA'ITERJEE
and status of libido were recorded every 2 weeks, and physical examinations were repeated periodically. In semen and blood samples, the investigations carried out were similar to those described in our earlier publication. 2 In the two wives who had been tubectomized postcoital tests were performed and in the other wife a modified Kremer's test was carried out to determine the cervical mucuspenetrating ability of the spermatozoa.
S.S. (32 VIif.)
RESULTS AND DISCUSSION
The daily administration of 10 mg of cyproterone acetate caused a progressive decrease in the count and motility of spermatozoa in all three subjects with a concomitant increase in abnormal and immature forms (Fig. 1). In all subjects the levels of seminal acid phosphatase and GPC were markedly decreased, but the levels offructose and sialic acid were not significantly altered. During CPA therapy the ability of the spermatozoa to penetrate preovulatory cervical mucus, as revealed by in vivo postcoital tests in two cases and by an in vitro modified Kremer's test in the other, was also decreased. There was no decrease in coital frequency, libido, or potency. The concurrent administration of mesterolone significantly counteracted the CPA-induced morphologic and biochemical changes in semen. Although the sperm count did not return to control levels, the levels of seminal acid phosphatase, fructose, and sialic acid were further stimulated in two volunteers who received combined treatment for 12 and 13 weeks. In one voiunteer (S. S.) who received combined treatment for only 7 weeks as he had to leave the city unexpectedly, the responses were less marked. The values for the postcoital tests and the modified Kremer's test returned to control levels during this period. During combined therapy all three men noted an increase in sexual desire. The blood levels of alkaline phosphatase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, urea, and creatinine did not show any significant change. The levels of serum glutamic-oxaloacetic transaminase were slightly elevated during combined therapy, but the values were within the normal range.
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FERTIUTY AND STERIUTY
Vol. 32, No.1, July 1979 Printed in U.s A.
Copyright" 1979 The American Fertility Society
THE ROLE OF ANTIANDROGENICACTION IN CYPROTERONE ACETATE-INDUCED MORPHOLOGIC AND BIOCHEMICAL CHANGES IN HUMAN SEMEN
SOMNATH ROY, M.B.B.S., PH.D.* SUDHA CHATTERJEE, M.Sc., PH.D. Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, New Delhi 110016, India
Following the daily administration of 10 mg of cyproterone acetate to three normal fertile human volunteers for 12 to 16 weeks, there was a marked decrease in the count ~otility, and cervical mucus-penetrating ability of spermatozoa, with a concomitant ' mcrease in abnormal and immature forms. The levels of seminal acid phosphatase and glycerylphosphoryl choline were also significantly decreased. Subsequently, concurrer:t daily administration of 75 mg of mesterolone increased the count, motility, and cervzcal mucus-penetrating ability of spermatozoa and stimulated the seminal biochemical constituents. The results indicate that the effects of a low dose of cyproterone acetate are due mainly to peripheral androgen deprivation. Fertil Steril 32:93, 1979
High doses (100 to 200 mg daily) of cyproterone acetate (1 ,2a-methylene-6-chloropregn-4,6-diene17 a-ol-3,20-dione-17 a-acetate), which is a very potent progestogen with a strong antiandrogenic property, inhibits spermatogenesis, libido, and potency in men. 1 It consistently decreases the levels of plasma testosterone, with or without a decrease in the levels offollicle-stimulating hormone (FSH) but no concomitant decrease in the levels of plasma or urinary luteinizing hormone (LH).2 The administration oflow doses (5, 10, and 20 mg daily) of this drug to men causes a decrease in the count and motility of spermatozoa and in thebiochemical constituents of semen with no significant change in libido and potency.2. 3 The blood levels of testosterone are decreased, but the levels of FSH and LH are not altered. 3 Since it has been suggested that the effects of low doses of cyproterone acetate are mainly due to its antiandrogenic action,2 the present investigation was undertaken to determine whether the concurrent administration of androgen could reverse the cyp-
roterone acetate-induced morphologic and biochemical changes in human semen. MATERIALS AND METHODS
Three normal fertile human male volunteers between 32 and 35 years of age were enrolled for the study. The wives of two of them had been tubectomized 2 years earlier. During the control period, three to six semen samples were collected every 2 weeks with 3 days' abstinence prior to each interval, and two blood samples were obtained at 4week intervals. The volunteers received daily 10 mg of cyproterone acetate (CPA) orally, and samples of semen and blood were obtained according to the above schedule. When a marked decrease in the count and motility of the spermatozoa was noted during CPA therapy, daily oral administration of 75 mg of mesterolone, an androgen with little gonadotropin-suppressing action, was started. This combined therapy, which was started at 16, 14, and 12 weeks, respectively, after the initiation of CPA treatment, continued for 7, 12, and 13 weeks, respectively. During this period semen samples were collected at weekly intervals, but the blood samples were obtained at 4-week intervals. General well-being, coital frequency,
Received April 25, 1978; revised March 5, 1979; accepted March 12, 1979. *Professor and Head, Department of Reproductive Biomedicine. To whom reprint requests should be addressed.
93
-----~---~--~----~~'--.........;
94
July 1979
ROY AND CHA'ITERJEE
and status of libido were recorded every 2 weeks, and physical examinations were repeated periodically. In semen and blood samples, the investigations carried out were similar to those described in our earlier publication. 2 In the two wives who had been tubectomized postcoital tests were performed and in the other wife a modified Kremer's test was carried out to determine the cervical mucuspenetrating ability of the spermatozoa.
S.S. (32 VIif.)
RESULTS AND DISCUSSION
The daily administration of 10 mg of cyproterone acetate caused a progressive decrease in the count and motility of spermatozoa in all three subjects with a concomitant increase in abnormal and immature forms (Fig. 1). In all subjects the levels of seminal acid phosphatase and GPC were markedly decreased, but the levels offructose and sialic acid were not significantly altered. During CPA therapy the ability of the spermatozoa to penetrate preovulatory cervical mucus, as revealed by in vivo postcoital tests in two cases and by an in vitro modified Kremer's test in the other, was also decreased. There was no decrease in coital frequency, libido, or potency. The concurrent administration of mesterolone significantly counteracted the CPA-induced morphologic and biochemical changes in semen. Although the sperm count did not return to control levels, the levels of seminal acid phosphatase, fructose, and sialic acid were further stimulated in two volunteers who received combined treatment for 12 and 13 weeks. In one voiunteer (S. S.) who received combined treatment for only 7 weeks as he had to leave the city unexpectedly, the responses were less marked. The values for the postcoital tests and the modified Kremer's test returned to control levels during this period. During combined therapy all three men noted an increase in sexual desire. The blood levels of alkaline phosphatase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, urea, and creatinine did not show any significant change. The levels of serum glutamic-oxaloacetic transaminase were slightly elevated during combined therapy, but the values were within the normal range.
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