Anabolic steroids and semen parameters in bodybuilders

Vol. 52, No.6, December 1989

FERTILITY AND STERILITY

Printed on acid-free paper in U.S.A.

Copyright C> 1989 The American Fertility Society

Anabolic steroids and semen parameters in bodybuilders

Ulrich A. Knuth, Dr.med. Harald Maniera, Cand.med. Eberhard Nieschlag, Prof. Dr.med. * Max Planck Clinical Research Unit for Reproductive Medicine and Institute of Reproductive Medicine of the University, Munster, Federal Republic of Germany

The influence of high-dose anabolic steroid administration on endocrine and semen parameters of 41 bodybuilders (age, 26.7 ± 0.7 years [mean ± SEM]; height, 182 ± 1 cm; weight, 97.5 ± 2.0 kg) was investigated. History of anabolic steroid administration was recorded retrospectively, and results of semen analysis were compared with data from 41 consecutively recruited normal volunteers not using any steroids or other drugs. Doses of anabolic steroids taken by bodybuilders exceeded those generally applied for clinical purposes by up to 40-fold. Although only 5 of the normal volunteers had sperm counts below the lower normal limit of 20 X 106 sperm/mL, 24 of the bodybuilders showed subnormal values. Depending on the duration of anabolic steroid use and the period since last drug intake before the investigation, percentages of motile and normally formed sperm were significantly reduced in bodybuilders compared with normal volunteers. In those bodybuilders who had stopped consumption of anabolic steroids> 4 months previously, sperm numbers were in the normal range. Results suggest that even after prolonged use of extremely high doses of anabolic steroids, sperm production may return to normal. Fertil SteriI52:1041, 1989

Administration of steroids at doses used frequentlyby athletes is so high that controlled clinical studies under similar conditions appear prohibited for ethical reasons. The possibility of impaired liver function during anabolic steroid treatment is well documented,I,2 and both malignant and benign liver tumors and peliosis hepatis have been reported in relation to the use of anabolic steroids (for review, see Reference 3). Thus the only way to detect long-term effects of high-dose administration of anabolic steroids is the use of retrospective case-control studies. 4 In the present cross-sectional investigation, we used this approach to elucidate the influence of anabolic steroids on seminal and reproductive endocrine parameters in bodybuilders.

Received April 3, 1989; revised and accepted July 27, 1989. * Reprint requests: Eberhard Nieschlag, Prof. Dr.med., Institute of Reproductive Medicine of the University, Steinfurter Strasse 107,4400 Miinster, Federal Republic of Germany. Vol. 52, No.6, December 1989

MATERIALS AND METHODS Recruitment

Contacts with bodybuilding studios were established by one of the authors (H.M.), who is an active athlete himself. The aim of the study was explained to potential volunteers. Free medical examination, hormone investigation, and semen analysis were offered. Study Design

Forty-one bodybuilders (age, 26.7 ± 0.7 years [mean ± SEM]; height, 182 ± 1 cm; weight, 97.5 ± 2.0 kg) agreed to participate. They were asked to complete a detailed questionnaire on history of drug intake, diet habits, and training performance. These questionnaires formed the basis for the final interview concerning information as detailed as possible about time course, doses, and kind of drugs taken in the past. In addition, a detailed medical Knuth et aI. Anabolic steroids and semen parameters

1041

Table 1

Generic and Trade Names of Anabolic Steroids Used by 41 Bodybuilders Investigated in the Present Study Systematic name

Injectable substances Testosterone-derived 17tJ- Hydroxyandrost-4-en -3-one

Generic name + ester

Testosterone propionate

cyclopentylpropionate enanthate

Trade name

Testoviron Oreton Durateston Depot testosterone cypionate Delatestryl Testoviron Depot

4-Chloro-17tJ-hydroxy-androst-4en-3-one

Mixture of propionate phenylpropionate decanoate isocapronate Clostebol acetate

Omnadren Sustanon

Steranabol Megagrisevit

17tJ-Hydroxy-androsta-1,4-dien-3one

Boldenone

Boldane Equipoise

19-N ortestosterone-derived 17tJ-Hydroxyestr-4-en-3-one

Nandrolone phenylpropionate hexyloxyphenylpropionate laurate decanoate

4,17tJ-Dihydroxyestr-4-en-3-one

Oxabolone

17tJ- Hydroxy-estratrien-4,9,l1-3-

Trenbolone

Durabolin Nerobolil Superanabol Anadur Laurabolil Deca-Durabolin Retabolil Steranabol-Depot

Manufacturer/location

Schering, Berlin, Federal Republic of Germany Schering, Berlin, Federal Republic of Germany Organon, Oss, Netherlands Upjohn, Heppenheim, Federal Republic of Germany Squibb, Frankfurt, Federal Republic of Germany Schering, Berlin, Federal Republic of Germany Organon, Oss, Netherlands Polva-Chemie, Warsaw, Poland

Farmitalia, Freiburg, Federal Republic of Germany Farmitalia, Freiburg, Federal Republic of Germany Squibb, Frankfurt, Federal Republic of Germany Squibb, Frankfurt, Federal Republic of Germany Organon, Oss, Netherlands Richter, Milano, Italy Pharmacia, Helsingborg Sweden Organon, Oss, Netherlands Organon, Oss, Netherlands Richter, Milano, Italy Farmitalia, Freiburg, Federal Republic of Germany

one acetate

Finaject

cyclohexylacetate

Parabolone

Heterocyclic anabolic steroids 17a-Methyl-5a-androstano-[3,2-c Jpyrazol-17tJ-ol

Stanozolol

Miscellaneous structure 17tJ-Hydroxy-1-methyl-5a-androst1-en-3-one

Methenolone

Substances for oral use Testosterone-derived 17tJ- Hydroxyandrost-4-en-3-one 17tJ- Hydroxy-17 -methyl-androsta-

Strombaject

Winthrop, Norderstedt, Federal Republic of Germany

Acetate

Primobolan

Enanthate

Primobolan Depot

Schering, Berlin, Federal Republic of Germany Schering, Berlin, Federal Republic of Germany

Testosterone undecanoate Methandrostenolone

Andriol Dianabol

1,4-dien -3-one Nerobil Metanabol

1042

Hoechst, Frankfurt, Federal Republic of Germany Negmar

Knuth et al. Anabolic steroids and semen parameters

Organon, Oss, Netherlands Ciba, Wehr, Federal Republic of Germany Richter, Milano, Italy Polva-Chemie, Warsaw, Poland

Fertility and Sterility

Table 1 (Continued) Systematic name

Generic name + ester

Trade name

Manufacturer/location

19-Nortestosterone-derived 17p-Hydroxy-19-norpregn-4-en-3one

Norethandrolone

Nilevar

Searle, Dreieich-Sprintlingen, Federal Republic of Germany

Androstane-derived 17P-Hydroxy-1a-methyl-5aandrostan-3-one

Mesterolone

Proviron

Schering, Berlin, Federal Republic of Germany Schering, Berlin, Federal Republic of Germany Griinenthal, Stolberg, Federal Republic of Germany

Mestoran 17P-Hydroxy-17-methyl2(hydroxymethylene )-5a-androstan-3-one

Heterocyclic anabolic steroids 17a-Methyl-5a-androstano-[3,2-c]pyrazol-17p-ol

Oxymetholone

Stanozolol

Plenastril Oxytosona Anadrol Androyd

Syntex, Palo Alto, California Syntex, Palo Alto, California

Winstrol

Winthrop, Norderstedt, Federal Republic of Germany Winthrop, Norderstedt, Federal Republic of Germany Searle, Dreieich-Sprintlingen, Federal Republic of Germany

Stromba 17p-Hydroxy-1-methyl-5a-androst1-en-3-one Miscellaneous structure 17p-Hydroxy-1-methyl-5a-androst1-en-3-one

Oxandrolone

Omnisterin Anavar

Methenolone

Primobolan

history was taken with special reference to reproductive function and gynecomastia. During physical examination testicular size was determined by comparison with an orchidometer. Varicoceles were excluded by palpation and Valsalva maneuver. A blood sample for endocrine parameters was drawn from an antecubital vein, and a semen specimen obtained by masturbation at the hospital was analyzed according to World Health Organization (WHO) guidelines5 after 48 hours to 5 days of sexual abstinence. The mean time of abstinence was 2.7 ± 0.4 days. In cases of extremely low sperm counts, the ejaculates were centrifuged and analyses performed on the sediment. Data from semen analysis in athletes were compared with results from a group of normal, drugfree volunteers (n = 41; age, 25.9 ± 0.5 years; weight, 80.7 ± 2.9 kg; height, 184 ± 1 cm) screened consecutively during the recruitment phase of a different study.s These semen samples were analyzed by the same technicians around 6 months earlier. Hormone Measurements

Serum for the endocrine evaluation was separated at 800 X g and stored at -20°C until assayed. Serum -luteinizing hormone (LH), follicle-stimuVol. 52, No.6, December 1989

Schering, Berlin, Federal Republic of Germany

lating hormone (FSH), and estradiol (E2) were determined in duplicate by radioimmunoassay (RIA). The detection limits for FSH and LH were 1.0 and 1.5 U/L, respectively. World Health Organization International Reference Preparations (IRPs) 68/ 40 and 78/549 were used as standards for LH and FSH, respectively. Testosterone (T) and dihydrotestosterone (DHT) were measured by RIA7 after isolation and separation by high-performance liquid chromatography to avoid cross-reactivity of unknown steroid metabolites. Steroid concentrations are given in international units. For conversion to nanograms per deciliter, multiply T values by 28.9; E2 values multiplied by 3.7 give results in picograms per milliliter. Statistics

Statistical analysis was performed on a Zeilith AT personal computer using the SPSS PC+ program (SPSS, Inc., Chicago, IL). Throughout the paper means ± SEM are used. Values of sperm concentrations were normalized by square root transformation. To detect differences in measured parameters among individual groups, analysis of variance (ANOVA) followed by a Student-Newman-Keul (SNK) test was applied. For the purpose of data reduction and further Knuth et aI. Anabolic steroids and semen parameters

1043

analysis, three subgroups were formed within the group of bodybuilders. Allocation was based on the time course of anabolic steroid administration and duration ofthe spermatogenic cycle. Nineteen men were still taking anabolic steroids when the investigation was performed. Eight of them had been taking steroids for only ~2 months after a drug-free interval from 1 to 5 months, together with 3 additional men who had stopped anabolic steroid administration between 1 and 3 months earlier after a treatment phase of only 2 months. These 11 men were considered to be most likely in an incomplete phase of spermatogenic suppression and were classified as group I. Group II comprised those 11 athletes who reported uninterrupted administration of anabolic steroids for 3 to 12 months up to the time of investigation and another 8 bodybuilders who had stopped taking steroids within the last 3 months after continuous administration for 3 to 9 months. In these men (n = 19), a maximal inhibition of spermatogenesis was expected. Group III was formed by the remaining 11 athletes, who had abandoned the use of anabolic drugs for >4 months before semen analysis.

RESULTS Steroids and Doses

Details of the steroids taken are given in Table 1. Testosterone and 19-nortestosterone esters were used most frequently, followed by methandrostenolone, methenolone acetate, and stanozolol (Table 2). Based on the duration of administration over the last 12 months, these five steroids comprised around 88% of anabolics used. In addition, trenbolone, boldenone, oxandrolone, chlorotestosterone mesterolone, and oxymetholone were used. Three men had used human chorionic gonadotropin (hCG) at doses of 1,500 to 3,000 IV on one or two occasions to stimulate endogenous T production. On average, the amounts of anabolic steroids taken per month were considerably higher than therapeutically recommended doses and reached extreme ranges in some men (Fig. 1). As a general pattern, different anabolic steroids were taken simultaneously for intervals of 3 to 4 months, interrupted by drug-free periods of similar length. This "stacking," as referred to by the athletes themselves, increased the total drug exposure per month even more. 1044

Knuth et al.

Anabolic steroids and semen parameters

Side Effects and Semen Parameters

In spite of these enormous doses, no side effects were reported, and only one man revealed gynecomastia during the physical examination. Compared with the control group of normal men, in which only two volunteers showed severe oligozoospermia (sperm concentrations < 5 X 106 jmL) in addition to three men with sperm concentrations between 5 and 20 X 106 jmL (moderate oligozoospermia), sperm concentrations in bodybuilders taking anabolic steroids were severely impaired (Fig. 2). There was no difference in semen volume between controls and "bodybuilders" (3.9 ± 0.2 versus 3.8 ± 0.3 mL; P > 0.05). In group I (n = 11), one man was azoospermic, three showed severe oligozoospermia, and one revealed sperm concentrations in the oligozoospermic range. Percentage of motile sperm in athletes with detectable sperm was significantly impaired in comparison with the control group, whereas no differences could be detected for the proportion of normally formed sperm. Within group II (n = 19), in which the most serious impact on spermatogenesis was expected, 7 men were azoospermic, 2 had only single sperm per high-power field in the sediments of their ejaculates, 5 were severely oligospermic, and 2 showed moderately impaired sperm concentrations. However, in spite oflong-Iasting steroid administration at high doses, 2 athletes revealed normal sperm concentrations at 41.8 and 71.0 X 106 jmL, respectively. In comparison with controls, percentage of motile as well as normally formed sperm was significantly reduced in this group. In contrast to those men allocated to groups I and II, athletes in group III (n = 11), who had stopped the usage of anabolic steroids for >4 months, had sperm concentrations within the range of normal controls. Only 3 men were severely oligozoospermic and 1 showed moderate oligozoospermia. However, a significant reduction in sperm motility and morphology compared with normal controls was apparent (Fig. 2). Hormone VaIues

Those men still taking anabolic steroids when tested (n = 19) showed significantly reduced values for LH (1.9 ± 0.3 V) and FSH (1.4 ± 0.2 V) compared with athletes, who had stopped drug consumption >4 months previously (n = 11; LH, 4.5 ± 1.1 V; FSH, 3.2 ± 0.5 V;P<0.05).Allotherbodybuilders (n = 11) with a drug-free interval of <3 Fertility and Sterility

Table 2

Anabolic Steroids Taken by 41 Bodybuilders Drug

Steroid use Total months of overall use Average use/ month (mg) I Highest dose used/month (mg)

TEa

OX h

CL'

MSi

Oyk

7

7

5

5

4

563 ± 103

864 ± 195

759 ± 255

376 ±97

880 ± 125

1,225 ±522

1,800

1,500

2,075

640

1,200

3,000

NT b

MAc

MEd

104

64

63

46

38

15

1,226 ± 125

554 ±68

690 ±82

1,098 ± 180

937 ± 109

10,550

3,000

4,500

7,500

3,000

ST'

BOg

TR'

a TE, testosterone esters. b NT, 19-nortestosterone esters. c MA, methandrostenolone. d ME, methenolone. eST, stanazolol. 'TR, trenbolone.

BO, boldenone. OX, oxandrolone. i CL, clostebol. i MS, mesterolone. k OY, oxymetholone. I Values for average use are means ± SEM. g

h

months showed intermediate values not different statistically from values given above (LH, 2.7 ± 0.6 U; FSH, 2.1 ± 0.6 U). No statistically significant differences could be detected for serum T (25.3 ± 5.9 versus 16.1 ± 5.1 versus 13.2 ± 1.8 nmol/L) and DHT concentrations (2.7 ± 0.3 versus 2.7 ± 0.9 versus 2.0 ± 0.3 nmol/L) depending on duration of the drug-free interval due to high variations within groups (ANOVA: P > 0.05). However, those men who were still taking anabolic steroids revealed significantly increased serum E2 concentrations (274 ± 21 pmol/L) compared with men with ~4 months of drug abstinence (184 ± 17 pmol/L; SNK: P < 0.05). Drug-free intervals of ~3 months in athletes were accompanied by E2 serum levels not different from both other groups (211 ± 9.6 pmol/L). ,......., m

DISCUSSION

Today the use of anabolic steroids among athletes has reached almost epidemic proportions, as revealed by the last olympic games. s Although a wealth of literature exists about their influence on athletic performance and side effects,3 the use of anabolic steroids by athletes is still quite controversial. Many men interviewed during the present study were convinced that strength and performance were improved by the use of anabolic steroids, although in general, this notion is not supported by the available scientific publications (for review, see Reference 3). However, well-controlled randomized trials under double blind conditions are difficult to perform, because athletes seem to be able to differentiate anabolic steroid treatment from placebo administration and use exceedingly

12000

• •

!. 10000

D

CD

.:::t.

.E

8000

~

6000

c

Figure 1 Comparison of clinically used doses (according to manufacturer's recommendations) versus mean and maximal monthly doses of some anabolic steroid used by bodybuilders. The mean represents the average dose taken by all men, whereas the maximal dose represents the highest consumption by one individual in the study. For abbreviations of steroids, see Table 2. Vol. 52, No.6, December 1989

o

maximal average

dose used by bodybuilder

clinical dose

~

.....U1CD

4000

>L..... C

o

E

2000

o

TE

NT

-

ME

ST anabolic steroid

Knuth et al.

ox

Anabolic steroids and semen parameters

1045

120 '=' E ....., ~

=E ......

M ...... C» 0

E .......

~

E

.2 D

~

c u c 0 u

.,•a..

41

11

19 11

c,d

41

10

10 11

100

>-

--• C

n:

a

80

a,b

a,b,c

.r.

a.. ~

0

60

>= ;:

40

0

20 0

sperm conc.

motility

morphology

Figure 2 Sperm concentration (mean ± SEM), percentage of motile sperm, and proportion of normally formed sperm in controls (black bars) in bodybuilders with short duration of anabolic steroid consumption (group I of text, hatched bars), in bodybuilders with extended anabolic steroid consumption (group II of text, horizontaUy lined bars), and in athletes after >4 months of drug-free interval (group III of text, open bars). Identical letters above two bars indicate those pairs of values that are statistically different by analysis of variance and SNK test. For analysis of motility and morphology, azoospermic ejaculates were treated like missing values.

high doses that clinical investigators find difficult to administer for ethical reasons. Androgenic steroids are known to cause impaired spermatogenesis.9 19-Nortestosterone has even been suggested for male contraception. lo.n Although the suppressive effects of anabolic steroids on testosterone and gonadotropin secretion have been studied to some extent, detailed trials on their influence on spermatogenesis are virtually nonexistent. In most instances, only endocrine parameters were measured. l2- l8 A general decrease of gonadotropins was reported, which is confirmed by our data. Spermatogenesis is under the control of FSH and LH, whose secretion is regulated by gonadal steroids and possibly by inhibin. Based on this negative feedback mechanism, administration of anabolic steroids suppresses gonadotropin secretion. Although this is the principle underlying an endocrine approach to male contraception with androgenic steroids (for review, see References 19 and 20), only few studies report seminal parameters in athletes using anabolic steroids. Studies are limited to case reports l4 or were conducted after too short a duration of treatment. 2l.22 The only controlled trials on the influence of anabolic steroids on seminal parameters used 19-nortestosterone at moderate doses with the aim of developing a male antifertility agent. lo.n In these trials, azoospermia or severe oligozoospermia with sperm counts < 5 X 106 /mL was observed in 83% of all participants. 23 In the present study, this value was shown by 65% of those 26 men who had taken anabolic steroids 1046

Knuth et al. Anabolic steroids and semen parameters

long enough immediately before the investigation so that an impact on spermatogenesis could be expected. As in trials with steroids for male contraception (for review, see References 19 and 20), some men were able to maintain spermatogenesis in spite of long-term steroid administration at high doses. This could corroborate the hypothesis that androgens alone may be sufficient to maintain or reinitiate spermatogenesis,24.25 although the diversity of compounds and doses used and their unknown metabolism complicate a definite conclusion. Most of the athletes in subgroup III (7/10) who had stopped taking anabolic steroids > 3 months before the investigation showed sperm counts> 20 X 106 /mL, the lower limit of normality according to the WHO guidelines. 5 Two athletes with sperm counts at 3.6 and 6.1 X 106/mL had ceased anabolic steroid usage 4 and 6 months earlier. Only 1 man displayed severely suppressed sperm concentrations 12 months after the latest use of anabolic steroids. Although the rate of 30% oligozoospermia in exusers of anabolic steroids versus 12% in unselected normal volunteers seems higher, numbers of subjects are small and normalization of spermatogenesis after trials for hormonal male antifertility agents may take >1 year. Apparent recovery time is severely influenced by the half-life of anabolic steroids used, which may be extremely long, as in the case of some 19-nortestosterone esters.n The reported results of the present study are based on data of anabolic steroid use in bodybuildFertility and Sterility

ers collected retrospectively and suffer from all disadvantages of this type of uncontrolled studies. In addition to the wide variety of drugs used, their different doses and durations of administration, diet habits, and training conditions may affect the results. It did not seem reasonable to put these factors into account systematically, because the report consists basically of 41 independent case studies. Within these limitations, however, the data suggest that in spite of severe suppression of gonadotropins, spermatogenesis may still continue in some men when high amounts of androgens are administered exogenously. Even after prolonged use of high doses of anabolic steroids, sperm production may return to normal levels. Ackrwwledgments. Semen analyses and hormone determinations were performed by Christa Kriisemann, Ingrid Upmann, Ulrike Oberdiek, and Mathilde Moller. Language editing was provided by Susan Nieschlag, M.A. (all working at Institute of Reproductive Medicine, Miinster).

REFERENCES 1. O'Shea JP, Winkler W: Biochemical and physical effects of an anabolic steroid in competitive swimmers and weight lifters. Nutr Rep Int 2:351, 1970 2. Shephard RJ, Killinger D, Fried T: Responses to sustained use of anabolic steroid. Br J Sports Med 11:170, 1977 3. Haupt HA, Rovere GD: Anabolic steroids: a review of the literature. Am J Sports Med 12:469, 1984 4. Cowar VS: Study proposes to examine football players, power lifters for possible long term sequelae from anabolic steroid use in 1970s competition. J Am Med Assoc 257: 3021,1987 5. World Health Organization: WHO Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction. Cambridge, The Press Syndicate of the University of Cambridge, 1987 6. Knuth UA, Kiihne J, Crosby J, Bals-Pratsch M, Kelly RW, Nieschlag E: Indomethacin and oxaprozin lower seminal prostaglandin levels but do not influence sperm motion characteristics and serum hormones of young healthy men in a placebo controlled double-blind trial. J Androl10:108, 1989 7. Belkien L, Schiirmeyer T, Hano R, Gunnarsson PO, Nieschlag E: Pharmacokinetics of 19-nortestosterone esters in normal men. J Steroid Biochem 22:623, 1985 8. Marshall E: The drug of champions. Science (Wash DC) 242:183, 1988 9. Heller CG, Nelson WO, Hill IB, Henderson E, Maddock WO, Jungck EC, Paulsen CA, Mortimer GE: Improvement in spermatogenesis following depression of human testis with testosterone. Fertil Steril1:415, 1950

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10. Schiirmeyer Th, Knuth UA, Belkien L, Nieschlag E: Reversible azoospermia induced by the anabolic steroid 19nortestosterone. Lancet 1:417, 1984 11. Knuth UA, Behre H, Belkien L, Bents H, Nieschlag E: Clinical trial of 19-nortestosterone hexoxyphenyl propionate (Anadur) for male fertility regulation. Fertil Steril44: 814,1985 12. Fahey TD, Brown CH: The effects of an anabolic steroid on the strength, body composition, and endurance of college males when accompanied by a weight training program. Med Sci Sports 5:272, 1973 13. Stromme SB, Meen HD, Aakvaag A: Effects of an androgenicanabolic steroid on strength development and plasma testosterone levels in normal males. Med Sci Sports 6:203, 1974 14. Kilshaw BH, Harkness RA, Hobson BM, Smith A WM: The effect of large doses of the anabolic steroid methandrostenolone on an athlete. Clin EndocrinoI4:537, 1975 15. Hervey GR, Hutchinson I, Knibbs AV, Burkinshaw L, Jones PRM, Norgan NG, Levell MJ: Anabolic effects of methandienone in men undergoing athletic training. Lancet 2:699, 1976 16. Holma PK, Adlercreutz H: Effect of an anabolic steroid (metandienone) on plasma LH, FSH, and testosterone and on the response to intravenous administration of LRH. Acta Endocrinol (Copenh) 83:856, 1976 17. Remes K, Vuopio P, Jarvinen M, Hiirl{onen M, Adlercreutz H: Effects of short-term treatment with an anabolic steroid (methandienone) and dihydroepiandrosterone sulphate on plasma hormones, res cell volume and 2,3 diphosphoglycerate in athletes. Scand J Clin Lab Invest 37:577, 1977 18. Clerico A, Ferdeghini M, Palombo C, Leoncini R, Del Chicca MG, Sardano G, Mariani G: Effect of anabolic treatment on serum levels of gonadotropins, testosterone, prolactin, thyroid hormones and myoglobin of male athletes under physical training. J Nucl Med Allied Sci 25:279, 1981 19. Knuth UA, Nieschlag E: Endocrine approach to male fertility control. Bailliere's Clin Endocrinol Metab 1:113, 1987 20. Nieschlag E, Weinbauer GF, Knuth UA: LHRH analogs and steroids for male fertility regulation. In Fertility Regulation Today and Tomorrow, Edited by E Diczfalusy, M Bygdeman. New York, Raven Press, 1987, p 233 21. Johnson LC, Fisher G, Silvester LJ, Hotheins CC: Anabolic steroid: effects on strength, body weight, oxygen uptake and spermatogenesis upon mature males. Med Sci Sports 4:43, 1972 22. Holma PK: Effects of an anabolic steroid (metandienone) on spermatogenesis. Contraception 15:151, 1977 23. Knuth UA, Behre H, Belkien L, Bents H, Nieschlag E: Clinical trials with 19-nortestosterone for male fertility control. In Male Contraception: Advances and Future Prospects, Edited by GI Zatuchni, A Goldsmith, JM Spieler, JJ Sciarra. Philadelphia, Harper and Row, 1986, p 320 24. Marshall GR, Wickings EJ, Liidecke DK, Nieschlag E: Stimulation of spermatogenesis in stalk-sectioned Rhesus monkeys by testosterone alone. J Clin Endocrinol Metab 57:152, 1983 25. Weinbauer GF, GOckeler E, Nieschlag E: Testosterone prevents complete suppression of spermatogenesis in the GnRH-antagonist treated non-human primate macaca fascicularis. J Clin Endocrinol Metab 67:284, 1988

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