The new totally synthetic progestational steroid norgestrel has been subjected to a clinical trial in gynaecological and endocrine cases and for oral contraception, and its toxicity and side-effects have been investigated. The effect of norgestrel alone and in combination with ethinyl oestradiol in various dosage/time schedules on the endometrium has been studied. The previous reports of its effectiveness in low dosage combinations with oestrogen with absence of significant side-effects or toxicity have been confirmed. These findings, together with its very high potency, make it an important addition to progestational therapy in gynaecological practice and for oral contraception.
The case of a male eunuchoid aged 32 years is described. Of 46 XY karyotype, his testes showed complete absence of spermatogenesis. Small immature hyalinized tubules were lined only with Sertoli cells, and Leydig cells were difficult to find. After treatment for 8 years with androgens, at first by injection and for the rest of the time by mouth, he developed full virilization and later fertility. His wife became pregnant and gave birth to a child with cyanotic congenital heart disease.
Four unusual cases of Klinefelter's syndrome are described, in which motile spermatozoa were found in several ejaculates. One of these subjects was shown to be a 47XXY/46XY mosaic, but intensive cytogenic studies in the other three failed to reveal evidence of this. Records of proven parenthood may eventually disturb the present concept of sterility in this condition.
In a double-blind clinical trial, 114 subfertile men were given courses of clomiphene citrate (100 mg daily for three 10-day periods in successive months) and of placebo tablets of identical appearance. There were no consistent changes in sperm density. No serious adverse reactions to clomiphene were seen. Further studies are recommended on the efficacy of clomiphene in doses of 25 to 50 mg daily for periods of 60 to 90 days.
Oral contraceptives containing oestrogen and progestagen in high dosage may produce many undesirable side effects. The risk of thrombo-phlebotic episodes (Vessey & Doll, 1969) has caused much concern, but the possible long-term effects of the numerous metabolic changes have also to be considered. Amongst the latter, impaired glucose tolerance (Wynn & Doar, 1969) and increased levels of serum glutamic—pyruvate transaminase (SGPT) have been reported (Larsson-Cohn, 1965).
The use of norgestrel alone, given continuously in low dosage of 50 μg, is slightly less effective as a contraceptive than conventional combinations of oestrogen and progestagen (Foss, Svendsen, Fotherby & Richards, 1968) and 22% of cycles are shorter than 23 days in the women on this regimen, but the incidence of side effects is much lower (Foss, 1968). With the elimination of the
The effect of clomiphene citrate on excretion values for fsh, lh, testosterone and epitestosterone has been investigated in four patients with Klinefelter's syndrome.
During the pretreatment period, levels of fsh and lh were above the normal range for male subjects, while readings of testosterone and epitestosterone were generally low.
Clomiphene produced a significant increase in fsh output in one subject and in lh excretion in another. In the remaining patients, pituitary gonadotrophic function was not affected by the administration of the compound. The effect of clomiphene on excretion values for C-19 steroids was inconsistent.
The study did not provide definite evidence regarding the site of of action of clomiphene in patients with Klinefelter's syndrome.
The effect of clomiphene on the sperm count and hormone excretion is described in a patient with Klinefelter's syndrome, having a 47 XXY karyotype, and in whom a testicular biopsy showed small areas of spermatogenesis.
Clomiphene stimulated the production of morphologically normal motile spermatozoa in the absence of any marked effect on hormone output.
Possible explanations for these findings are discussed.