Endocrine, seminal and peripheral effects of depot medroxyprogesterone acetate and testosterone enanthate in men.
Depot medroxyprogesterone acetate (D-MPA, 250 mg) and testosterone enanthate (TE, 200 mg) were administered twice with a 4-week interval to nine healthy men, and the levels in blood of steroids, gonadotrophins, lipoproteins, sex hormone binding globulin (SHBG) and prostaglandins (PGs) were measured, as well as steroid levels in semen and the sperm count and motility. The hormones analysed were: MPA, testosterone, androstenedione (A), dihydrotestosterone (DHT), oestradiol (E2), cortisol (C), luteinizing hormone (LH), follicle stimulating hormone (FSH) and the sulphoconjugated forms (-S) of testosterone, DHT, pregnenolone (5-P) and dehydroepiandrosterone (DHEA). Peak values of MPA (10.2 +/- 4.6 nmol/l) and testosterone (28.0 +/- 10.0) were found in the first blood samples 2 days after each injection. Thereafter the levels of MPA decreased gradually and reached the limit of detection 18-20 weeks after the second injection. Blood levels of testosterone fell sharply from the peak values and were grossly subnormal 2 weeks after each injection; levels did not return to pretreatment values during 24 weeks of follow-up. The pattern of change of DHT, A, E2 and sulphonated androgens was similar to that of testosterone. These data suggest that D-MPA and TE are absorbed at similar rates, and that the TE is metabolized rapidly. The subsequent reduction in the levels of A, testosterone-S and DHT-S was less marked and reached pretreatment values earlier than did the testosterone levels. No obvious changes were found in the levels of C, 5-P-S and DHEA-S or in the seminal plasma levels of the various steroids studied. The blood levels of LH and FSH fell precipitously 2 days after the first injection, then started to increase 4 weeks after the second injection to reach pretreatment values 12 weeks later. Of the lipoproteins studied only the levels of HDL-cholesterol and SHBG were found suppressed after treatment. Severe oligozoospermia and the complete absence of progressively motile sperm, in at least one semen sample, was observed in all subjects at 3-7 and at 5-16 weeks, respectively, after the last injection, suggesting that the men were infertile for at least 1 month after treatment. A spurious increase in the PG content of semen was also observed. In spite of the low blood testosterone levels, no subject reported changes in sexual behaviour or other signs of anabolic imbalance during or after the study. However, the increase in levels of E2 in some individuals should be kept in mind as a possible cause of side-effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Hedman
M
M
Reproductive Endocrinology Research Unit, Karolinska Sjukhuset, Stockholm, Sweden.
Gottlieb
C
C
Svanborg
K
K
Bygdeman
M
M
de la Torre
B
B
D000328:Adult; D000735:Androstenedione / Q000032:analysis; D003687:Dehydroepiandrosterone / Q000032:analysis; D003692:Delayed-Action Preparations; D013196:Dihydrotestosterone / Q000032:analysis; D004958:Estradiol / Q000032:analysis; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D008875:Middle Aged; D011284:Pregnenolone / Q000032:analysis; D012661:Semen / Q000032:analysis / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D003692:Delayed-Action Preparations; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D011284:Pregnenolone; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D006854:Hydrocortisone