To evaluate the utility of sperm tests as indicators of chemical effects on human spermatogenesis, the literature on 4 sperm tests used to assess chemically induced testicular dysfunction was reviewed. The tests surveyed included sperm count, motility, morphology (seminal cytology), and double Y-body (a fluorescence-based test thought to detect Y-chromosomal nondisjunction). There were 132 papers that provided sufficient data for evaluation. These reports encompassed 89 different chemical exposures: 53 were to single agents; 14 to complex mixtures; and 22 to combinations of 2 or more identified agents. Approximately 85% of the exposures were to experimental or therapeutic drugs, 10% were to occupational or environmental agents, and 5% were to drugs for personal use. The most common sperm parameter studied was sperm count (for 87 of the 89 exposures reviewed). Sperm motility was evaluated for 59 exposures, morphology for 44, and double Y-bodies for only 4. The 89 exposures reviewed were grouped into 4 classes: those which adversely effected spermatogenesis, as measured by one or more of the sperm tests (52); those suggestive of improving semen quality (11); those showing inconclusive evidence of adverse effects from exposure (14); and those showing no significant changes (12). Since the reviewed reports had a large variety of study designs, and since every attempt was made to include all reports with interpretable data, these classifications were based on reviewing committee decisions rather than on uniform statistical criteria. This review gives strong evidence that human sperm tests can be used to identify chemicals that affect sperm production, but because of our limited understanding of underlying mechanisms, the extent to which they can detect mutagens, carcinogens or agents that affect fertility remains uncertain. For the very few agents studied with both human and mouse sperm tests, similar test-responses were seen; thus sperm tests in mice and other laboratory mammals may have a potential role in hazard identification. An overall comparison of the 4 human sperm tests suggests that no one test is biologically more responsive than another; all of them may thus be needed when testing for chemically induced changes from agents of unknown activity. This review also gives evidence that sperm tests can be used to assess the extent and the potential reversibility of induced spermatogenic damage. The reviewing committee recommends further studies to determine (a) the dose-response characteristics of the human sperm tests, (b) details of the reversibility of induced changes with time after exposure, (c) the relative responses in the 4 sperm tests in exposed individuals, (d) the mechanism of action, (e) the biological and genetic implications of chemically induced effects, and (f) the comparison of responses among different species for risk assessment. The reviewing committee outlines specific considerations for planning new sperm studies on chemically exposed men.

An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

Twenty males participated in a 2-month study examining the relationship between 8 a.m. plasma testosterone levels and orgasmic frequency. Within subjects, higher levels of testosterone are associated with periods of sexual activity. Over subjects, however, the direction of the relationship is reversed. Mean testoster-one levels were higher for sexually less active individuals.

Orgasmic frequency and plasma testosterone levels in normal human males.

Summary— Forty-two patients with previously untreated T3/4 N1-4 MO/1 prostatic adenocarcinoma were treated with either cyproterone acetate (n=21; 300 mg intramuscularly per week) or oestradiol undecylate (n=21; 100 mg intramuscularly per month) after extensive staging which included open skeletal biopsy and pelvic lymphadenectomy in some cases. Subjective and objective parameters as well as signs of drug toxicity were recorded regularly.



Evaluation after 6 months showed cyproterone acetate to be more effective in the following respects: (1) the significantly different castration effect as judged by plasma testosterone, (2) the objective voiding pattern and tumour response, with regression of palpable and histologically evaluable local tumour in 16 of 21 patients, and (3) side effects and untoward reactions.



Thus cyproterone acetate is suggested as a valuable alternative in the treatment of advanced prostatic cancer.

Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial.

Antispermatogenic action of gossypol in men

Sex drive reducing therapies are employed in those cases of anomalous erotic preferences in which the patient's sexual behaviour is dangerous (certain forms of sadism, or a preference for forcing intercourse or similar interaction) or while not really dangerous, is utterly unacceptable to the community (pedophilia and pedohebephilia) or is an embarrassment to the patient himself (exhibitionism). Three sex drive reducing therapies are in use, all designed for male patients: (1) pharmacological reduction of circulating testosterone, (2) orchydectomy, (3) deletion of certain brain structures by stereotaxic surgery. The main indication for pharmacological sex drive reduction is exhibitionism but here it should be used only temporarily, as a first emergency measure, and after that only intermittently, during periods when the patient can not manage his urges by techniques he should be taught by a behaviour therapist. In cases of unmanageable and dangerous sadism, orchydectomy is the method of choice - and the same would appear to be true for particular cases of pedohebephilia. Brain surgery in this realm is not yet based on sufficient knowledge and should be thoroughly studied on infrahuman primates, before use with humans could be seriously considered.

Therapeutic Sex Drive Reduction

Cyproterone acetate (CA) was administered to a group of 6 normal healthy males in 2-100 mg doses daily continuously for a period of 16-20 weeks in order to test the effect of CA on the male reproductive system. This dosage is the norm for treatment of benign or malignant prostatic hypertrophy. Sperm counts fell off after an average of 8 weeks experimentation and reached the level of functional sterility by an average of 13 weeks. Morphological abnormality of the sperm increased over time. Sperm motility decreased. Libido and potency decreased sharply. All these functions returned to normal within a few weeks after administration of CA was stopped. The drug also caused moderate decreases in testicular germ cell numbers and testosterone levels of plasma and urine. No changes resulted in levels of plasma or urinary interstitial cell-stimulating hormone follicle stimulating hormone or in Leydig cell morphology or number. Liver and kidney functions continued normally. Indications are that the major site of inhibition is in the testis not in the epididymis or ductular system. Reduced testosterone level even without androgen deprivation could cause all of these changes. The indication is that CA is a powerful antifertility agent. The undesirable effects of loss of libido and impotency may be abolished by reducing the dosage. By maintaining a dosage of sufficient strength CA could be used as a male contraceptive.

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Effect of cyproterone acetate on sperm concentration, seminal fluid volume, testicular cytology and levels of plasma and urinary icsh, fsh and testosterone in normal men

H. C. Morse

Papers

Effect of cyproterone acetate on sperm concentration, seminal fluid volume, testicular cytology and levels of plasma and urinary icsh, fsh and testosterone in normal men