Archives of Andrology Journal of Reproductive Systems
ISSN: 0148-5016 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/iaan19
Local male hormonal therapy in male infertility: A preliminary report M. S. Fahim, S. M. Girgis, A. A. Ibrahim & A. Karaksy To cite this article: M. S. Fahim, S. M. Girgis, A. A. Ibrahim & A. Karaksy (1979) Local male hormonal therapy in male infertility: A preliminary report, Archives of Andrology, 3:2, 181-184, DOI: 10.3109/01485017908985068 To link to this article: http://dx.doi.org/10.3109/01485017908985068
Published online: 09 Jul 2009.
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Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iaan19 Download by: [University of California Santa Barbara]
Date: 19 March 2016, At: 02:32
Local Male Hormonal Therapy in Male Infertility: A Preliminary Report
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
M. S. FAHIM,S. M. GIRGIS,A. A. IBRAHIM, and A. KARAKSY The therapeutic effect of local infiltration of the testis by testosterone crystalline suspension was studied in 18 cases of severe oligozoospermia. Evaluation was done by semen analysis follow-up, and results were correlated with preoperative testicular biopsies. About 40% of the cases showed improvement of sperm count and/or motility. Testicular biopsies of responding cases showed mild inhibitory changes, such as sloughing or partial spermatogenic arrest at late stages, while cases with tubular hyalinization or spermatogenic arrest at the stage of spermatogonia showed no response. The method proved to be simple, safe, and promising. Key Words: Male infertility; Testosterone therapy; Oligozoosperrnia.
INTRODUCTION
Hormones act by combining with receptors in the target organs. In the testis, receptors for testosterone have been demonstrated in the Sertoli, Leydig, and spermatogenic cells [ 11. Under normal physiological conditions, testosterone produced by the Leydig cells will reach the receptors in the testis mainly by the blood stream. It is also possible that testosterone produced by the Leydig cells could act locally. The present communication is a preliminary report on the effect of intratesticular injection of testosterone on spermatogenic function. MATERIALS AND METHODS The study was conducted in 18 infertile patients suffering from severe oligozoospermia; infertility was determined on the basis of their inability to produce progeny. The age of the patients varied from 26 to 45 years with a mean of 34 years. All of the cases had primary sterility with marital duration varying from 2 to 20 years with a mean of 6.6 years. All of the patients had general good health, well-developed secondary characters, no apparent endocrinal disturbances, and no sexual complaints. Semen showed severe oligozoospermia with counts below 6 million/ml associated with impaired motility in 9 cases and necrospermia in the remaining 9 cases (Table 1). In 15 cases, local intratesticular injection was done after taking a testicular biopsy through the same opening in the tunica albuginea. In the remaining 3 cases, injection was done after infiltration of the cord and the subcutaneous tissue by local anesthetics. The injection material used was aqueous testosterone 50 mg/ml. In all cases, 0.5 mi was used to insuspension (17-beta-hydroxy-4-androsten-3-one), Received April 1979; revised June 19, 1979. From the Department of Obstetrics and Gynecology, University of Missouri Medical School, Columbia, Missouri and the Male Sterility Clinic and Andrology Section, Faculty of Medicine, Cairo University, Cairo, Egypt. Address reprint requests to: M. S. Fahim, Department of Obstetrics/Gynecology, University of Missouri Medical School, Columbia, MO, 65212, USA. 181 0 Elsevier North Holland, Inc., ARCHIVES OF ANDROLOGY 3, 181-184 (1979)
014k5016/79/060181-002.25
182 M. S. Pahim et al. TABLE 1 Summary of Semen Analysis Before and After Intratesticular Injection SEMENANALYSIS AFTER INJECTION
SEMEN ANALYSIS INJECTION
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
BEFORE
CASE No.
DEN-
Mo-
ABNOR-
DEN-
SITY'
TlLlTY'
MALITY
SITY"
1
5
20%
40%
2
1
0
3
4
4
2
5
4
6
2
7
Mo-
ABNOR-
RESPONSETO TREATMENT
TILITY"
MALITY
4
30%
40%
no response
50%
19
15%
30%
improved in both count and motility
10%
40%
18
0
30%
dissociate response: count improved, motility diminished
0
30%
2
0
30%
no response
35%
2
0
30%
no response
0
50%
2
0
50%
no response
4
20%
30%
19
30%
30%
improved, mostly in density
8
1
0
70%
1
0
75%
no response
9
2
0
70%
2
0
60%
no response
10
2
0
30%
2
0
60%
no response
11
3
10%
30%
3
10%
30%
no response
12
1
0
50%
1
0
50%
no response
13
6
15%
3wo
4
40%
20%
motility improved
14
3
0
60%
2
30%
40%
improved in both count and motility
15
3
10%
45%
6
20%
25%
improved in both count and motility
16
2.5
40%
30%
3
0
30%
no response
17
3
20%
20%
5
30%
20%
mild response in density and motility
18
1
0
25%
2
50%
25%
motility improved
'I
10%
Number of spermatozodml ( x 10").
* Analyzed 2 hours after ejaculation.
filtrate the testis. Testicular biopsy was obtained before treatment [2,3]. Semen examination was done before and 3 months after the local injection.
RESULTS In all cases, there were no postoperative complications or testicular discomfort. No ill effects were reported by the patients presenting themselves for a second examination 3
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
Male Hormonal Therapy in Male Infertility 183
months after the injection, and local examination of the scrotum showed no changes. Potency was reported as increased in seven patients and as no change in the remaining patients. Semen analysis 3 months after the injection showed that 8 cases improved in varying degrees (44%). Both density and motility increased in 4 cases, while density alone increased in another 2 cases and motility alone improved in the remaining 2 cases (Table 1). Correlation between testicular biopsy and semen showed that responding cases were those with biopsies showing mild changes, such as sloughing, hypercellularity , and partial spermatogenic arrest; 50% of such cases responded favorably. Cases with degenerative changes such as tubular hyalinization as well as cases showing spermatogenic arrest at early stages showed no response.
DISCUSSION Hormonal therapy through local injection at the site of the target organ seems to be logical since hormones are utilized by the corresponding receptors situated in the cytoplasm or on the cellular membranes. In the case of the male hormone, its receptors have been demonstrated in relation to the Sertoli cells which also bind the male hormone by a special protein (ADP) and later release it to the intratubular elements. Male hormone receptors are also present in Leydig cells, peritubular myoid cells, and spermatogenic cells [ 1,3,4]. A preliminary report regarding intratesticular implants of male hormone showed favorable response [ 5 ] . In the present work, aqueous crystalline suspension of testosterone was used to diminish absorption by the general circulation, thus allowing for long-acting local action. Semen analysis was repeated after 3 months to allow one spermatogenic cycle to be completed. No follow-up testicular biopsies were done, and the result of treatment was judged by semen analysis. No side effects were noticed, and the local injections were well tolerated. About 40% responded favorably with rise in both density and motility in half of the cases or in only one of the two parameters in the remaining cases. The rise in count was striking in 3 cases (Nos. 2 , 3 , and 7)-from 1 million to 19 million/ml in the first case, from 4 million to 18 million/ml in the second case, and from 4 million to 19 million/ml in the third case. Also, 3 cases (Nos. 2,14, and 17) with necrospermia showed motility after treatment reaching 15% in the first case, 30% in the second case, and 50% in the third case. Correlation with testicular biopsies showed that improvement is liable to occur in about 50% of the cases showing various inhibitory changes, such as sloughing, hypercellularity ,and spermatogenic arrest. Cases showing degenerative changes or spermatogenic arrest at the early stage of spermatogonia do not respond. Local hormonal intratesticular medication is a safe method of treatment that could be beneficial in cases of idiopathic oligozoospermia where testicular biopsies show mild spermatogenic inhibition. REFERENCES
1 . Hansson V , Djoseland 0, Torgersen 0, Ritzen EM, French FS, Nayfeh SN (1976a): Hormones and hormonal target cells in the testis. Andrologia 8: 195-202
2. Girgis SM, Etriby A, lbrahim AA, Kahil SA (1969): Testicular biopsy in azoospermia. Fertil Steril 20: 467-477 3. Girgis SM, Hafez ESE (1976): Evaluation of
184
M. S. Fahim et al.
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
testicular biopsy in azoospermia. In: Techniques of H u m a n Andrology, Hafez ESE (Ed.). Amsterdam: Elsevier North Holland, p 83 4. Hansson V, Caladra R, Purvis K, Ritzen M, French FS (l976b): Hormonal regulation of spermatogenesis. Vitamins Hormones 34: 187-214
5. Oshima H, Negishi T, Yokowa M, Ochi-Ai K (1977): Clinical evaluation of testosterone pellet implantation in the testis as a treatment of male infertility. In: The Testis in Normal and Infertile M e n , Troen P, Nankin HR (Eds.). New York: Raven Press, pp 561-563
ISSN: 0148-5016 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/iaan19
Local male hormonal therapy in male infertility: A preliminary report M. S. Fahim, S. M. Girgis, A. A. Ibrahim & A. Karaksy To cite this article: M. S. Fahim, S. M. Girgis, A. A. Ibrahim & A. Karaksy (1979) Local male hormonal therapy in male infertility: A preliminary report, Archives of Andrology, 3:2, 181-184, DOI: 10.3109/01485017908985068 To link to this article: http://dx.doi.org/10.3109/01485017908985068
Published online: 09 Jul 2009.
Submit your article to this journal
Article views: 3
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iaan19 Download by: [University of California Santa Barbara]
Date: 19 March 2016, At: 02:32
Local Male Hormonal Therapy in Male Infertility: A Preliminary Report
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
M. S. FAHIM,S. M. GIRGIS,A. A. IBRAHIM, and A. KARAKSY The therapeutic effect of local infiltration of the testis by testosterone crystalline suspension was studied in 18 cases of severe oligozoospermia. Evaluation was done by semen analysis follow-up, and results were correlated with preoperative testicular biopsies. About 40% of the cases showed improvement of sperm count and/or motility. Testicular biopsies of responding cases showed mild inhibitory changes, such as sloughing or partial spermatogenic arrest at late stages, while cases with tubular hyalinization or spermatogenic arrest at the stage of spermatogonia showed no response. The method proved to be simple, safe, and promising. Key Words: Male infertility; Testosterone therapy; Oligozoosperrnia.
INTRODUCTION
Hormones act by combining with receptors in the target organs. In the testis, receptors for testosterone have been demonstrated in the Sertoli, Leydig, and spermatogenic cells [ 11. Under normal physiological conditions, testosterone produced by the Leydig cells will reach the receptors in the testis mainly by the blood stream. It is also possible that testosterone produced by the Leydig cells could act locally. The present communication is a preliminary report on the effect of intratesticular injection of testosterone on spermatogenic function. MATERIALS AND METHODS The study was conducted in 18 infertile patients suffering from severe oligozoospermia; infertility was determined on the basis of their inability to produce progeny. The age of the patients varied from 26 to 45 years with a mean of 34 years. All of the cases had primary sterility with marital duration varying from 2 to 20 years with a mean of 6.6 years. All of the patients had general good health, well-developed secondary characters, no apparent endocrinal disturbances, and no sexual complaints. Semen showed severe oligozoospermia with counts below 6 million/ml associated with impaired motility in 9 cases and necrospermia in the remaining 9 cases (Table 1). In 15 cases, local intratesticular injection was done after taking a testicular biopsy through the same opening in the tunica albuginea. In the remaining 3 cases, injection was done after infiltration of the cord and the subcutaneous tissue by local anesthetics. The injection material used was aqueous testosterone 50 mg/ml. In all cases, 0.5 mi was used to insuspension (17-beta-hydroxy-4-androsten-3-one), Received April 1979; revised June 19, 1979. From the Department of Obstetrics and Gynecology, University of Missouri Medical School, Columbia, Missouri and the Male Sterility Clinic and Andrology Section, Faculty of Medicine, Cairo University, Cairo, Egypt. Address reprint requests to: M. S. Fahim, Department of Obstetrics/Gynecology, University of Missouri Medical School, Columbia, MO, 65212, USA. 181 0 Elsevier North Holland, Inc., ARCHIVES OF ANDROLOGY 3, 181-184 (1979)
014k5016/79/060181-002.25
182 M. S. Pahim et al. TABLE 1 Summary of Semen Analysis Before and After Intratesticular Injection SEMENANALYSIS AFTER INJECTION
SEMEN ANALYSIS INJECTION
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
BEFORE
CASE No.
DEN-
Mo-
ABNOR-
DEN-
SITY'
TlLlTY'
MALITY
SITY"
1
5
20%
40%
2
1
0
3
4
4
2
5
4
6
2
7
Mo-
ABNOR-
RESPONSETO TREATMENT
TILITY"
MALITY
4
30%
40%
no response
50%
19
15%
30%
improved in both count and motility
10%
40%
18
0
30%
dissociate response: count improved, motility diminished
0
30%
2
0
30%
no response
35%
2
0
30%
no response
0
50%
2
0
50%
no response
4
20%
30%
19
30%
30%
improved, mostly in density
8
1
0
70%
1
0
75%
no response
9
2
0
70%
2
0
60%
no response
10
2
0
30%
2
0
60%
no response
11
3
10%
30%
3
10%
30%
no response
12
1
0
50%
1
0
50%
no response
13
6
15%
3wo
4
40%
20%
motility improved
14
3
0
60%
2
30%
40%
improved in both count and motility
15
3
10%
45%
6
20%
25%
improved in both count and motility
16
2.5
40%
30%
3
0
30%
no response
17
3
20%
20%
5
30%
20%
mild response in density and motility
18
1
0
25%
2
50%
25%
motility improved
'I
10%
Number of spermatozodml ( x 10").
* Analyzed 2 hours after ejaculation.
filtrate the testis. Testicular biopsy was obtained before treatment [2,3]. Semen examination was done before and 3 months after the local injection.
RESULTS In all cases, there were no postoperative complications or testicular discomfort. No ill effects were reported by the patients presenting themselves for a second examination 3
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
Male Hormonal Therapy in Male Infertility 183
months after the injection, and local examination of the scrotum showed no changes. Potency was reported as increased in seven patients and as no change in the remaining patients. Semen analysis 3 months after the injection showed that 8 cases improved in varying degrees (44%). Both density and motility increased in 4 cases, while density alone increased in another 2 cases and motility alone improved in the remaining 2 cases (Table 1). Correlation between testicular biopsy and semen showed that responding cases were those with biopsies showing mild changes, such as sloughing, hypercellularity , and partial spermatogenic arrest; 50% of such cases responded favorably. Cases with degenerative changes such as tubular hyalinization as well as cases showing spermatogenic arrest at early stages showed no response.
DISCUSSION Hormonal therapy through local injection at the site of the target organ seems to be logical since hormones are utilized by the corresponding receptors situated in the cytoplasm or on the cellular membranes. In the case of the male hormone, its receptors have been demonstrated in relation to the Sertoli cells which also bind the male hormone by a special protein (ADP) and later release it to the intratubular elements. Male hormone receptors are also present in Leydig cells, peritubular myoid cells, and spermatogenic cells [ 1,3,4]. A preliminary report regarding intratesticular implants of male hormone showed favorable response [ 5 ] . In the present work, aqueous crystalline suspension of testosterone was used to diminish absorption by the general circulation, thus allowing for long-acting local action. Semen analysis was repeated after 3 months to allow one spermatogenic cycle to be completed. No follow-up testicular biopsies were done, and the result of treatment was judged by semen analysis. No side effects were noticed, and the local injections were well tolerated. About 40% responded favorably with rise in both density and motility in half of the cases or in only one of the two parameters in the remaining cases. The rise in count was striking in 3 cases (Nos. 2 , 3 , and 7)-from 1 million to 19 million/ml in the first case, from 4 million to 18 million/ml in the second case, and from 4 million to 19 million/ml in the third case. Also, 3 cases (Nos. 2,14, and 17) with necrospermia showed motility after treatment reaching 15% in the first case, 30% in the second case, and 50% in the third case. Correlation with testicular biopsies showed that improvement is liable to occur in about 50% of the cases showing various inhibitory changes, such as sloughing, hypercellularity ,and spermatogenic arrest. Cases showing degenerative changes or spermatogenic arrest at the early stage of spermatogonia do not respond. Local hormonal intratesticular medication is a safe method of treatment that could be beneficial in cases of idiopathic oligozoospermia where testicular biopsies show mild spermatogenic inhibition. REFERENCES
1 . Hansson V , Djoseland 0, Torgersen 0, Ritzen EM, French FS, Nayfeh SN (1976a): Hormones and hormonal target cells in the testis. Andrologia 8: 195-202
2. Girgis SM, Etriby A, lbrahim AA, Kahil SA (1969): Testicular biopsy in azoospermia. Fertil Steril 20: 467-477 3. Girgis SM, Hafez ESE (1976): Evaluation of
184
M. S. Fahim et al.
Downloaded by [University of California Santa Barbara] at 02:32 19 March 2016
testicular biopsy in azoospermia. In: Techniques of H u m a n Andrology, Hafez ESE (Ed.). Amsterdam: Elsevier North Holland, p 83 4. Hansson V, Caladra R, Purvis K, Ritzen M, French FS (l976b): Hormonal regulation of spermatogenesis. Vitamins Hormones 34: 187-214
5. Oshima H, Negishi T, Yokowa M, Ochi-Ai K (1977): Clinical evaluation of testosterone pellet implantation in the testis as a treatment of male infertility. In: The Testis in Normal and Infertile M e n , Troen P, Nankin HR (Eds.). New York: Raven Press, pp 561-563
