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Two 46 XY siblings with familial incomplete male pseudohermaphroditism, Type 2, inherited as an apparent autosomal recessive trait, were investigated. The phenotype was distinctive in that male wolffian-duct structures (epididymis, vas deferens and seminal vesicles) were present whereas tissues derived from the urogenital sinus and from the anlage of the external genitalia were female in character. Studies of estrogen and androgen dynamics revealed normal male blood testosterone and estrogen levels, production rates and interconversions. The normal blood luteinizing hormone level and normal estrogen production rate suggest that androgen resistance in this syndrome is different from that in other androgen-resistant states. The demonstration of markedly deficient dihydrotestosterone formation in slices of perineal skin, epididymis and phallus, considered with the fact that dihydrotestosterone is the fetal hormone responsible for male differentiation of the external genitalia, is compatible with the...

From 1960 to 1970 8 patients with metastatic choriocarcinoma of the testis were treated at the Naval Hospital in Long Beach California. The men ranged in age from 22 to 45 years. 6 patients had testicular enlargement 1 had hemoptysis and 1 had an abdominal mass. All patients were managed with chemotherapy using actinomycin D plus an aklylating agent (teytoxan or chlorambucil); 4 patients also received methotrexate. 3 patients underwent adjunctive radiotherapy to symptomatic masses. There were 4 patients who achieved regression of tumor 3 had no response and 1 has survived for 3 years. The average survival of patients who had tumor regression (6.5 months) was not significantly different from those who failed to respond (4 months). No objective response could be attributed to radiotherapy. The course of the surviving patients is summarized. The patient was initially managed with 25 mg diethylstilbestrol daily and 100 mg depo-provera every 2 weeks. A course of 25 mg oral methotrexate was given daily for 5 days with no objective response. The patient was then treated daily with 0.75 mg actinomycin D intravenously 300 mg cytoxan intravenously and 15 mg methotrexate orally in 5-day courses every 2 weeks. This regimen was well tolerated resulting only in alopecia and mild nausea. Marked regression in pulmonary metastases occurred 4 months after the initiation of this therapy. Subsequently maintenance chemotherapy was given in 5-day courses at monthly intervals. Depo-provera and diethylstilbestrol were discontinued after about a year because of impotence. Currently the patient is managed with 3-day courses of chemotherapy at monthly intervals.

We reviewed the records of 68 consecutive patients with localized or locally advanced prostate carcinoma treated with definitive radiation from 1959 through 1970. In patients followed over 5 years, the lymphatics within the true pelvis received at least 5000 rads in 5 to 6 1/2 weeks, and the primary received 6000 to 7500 rads in 7 to 11 weeks. There were 64% 5-year and 38% 10-year actuarial survivals, and clinical local control in 91% of the 5- to 12-year survivors (21/23). Additionally, negative prostate biopsies were obtained in 76% of the patients sampled more than 1-year after treatment (16/21). This report offers further evidence that carcinoma of the prostate, even if inoperable, is curable with radiation, but we could not demonstrate an improvement in 5-year survival, 10-year survival, or disease-free rate with pelvic nodal treatment.

The exact mechanisms involved in the feedback regulation of follicle stimulating hormone (FSH) in the male are uncertain. Although large doses of testosterone can suppress serum FSH levels, this effect may represent either a direct androgenic influence or an indirect one mediated by the peripheral conversion of testosterone to estrogen. In this study, the effect of an antiandrogen, cyproterone, on serum FSH levels was tested to further clarify whether androgens can directly influence the feedback regulation of FSH. Additionally, the ability of cyproterone to provide a luteinizing hormone (LH) reserve test in men is studied. In immature male rats, cyproterone 2 mg/d produced no effect on ventral prostate weight (VPW) but 10 mg/d suppressed VPW to 50% of control weight. Serum LH concentrations were increased by both doses of cyproterone, 22% by 2 mg and 40% by 10 mg; serum FSH was unchanged. In adult rats, cyproterone failed to decrease VPW but did increase serum LH 25% by 50 mg/d and 50% by 100 mg/d; again serum FSH was unchanged. In castrated adult rats, treatment with testosterone propionate 400 ng/d increased VPW and decreased serum LH and FSH concentrations; simultaneous treatment of these rats with cyproterone 30 mg/d decreased VPW by 41% and increased both serum LH and FSH (45 and 34%). In three adult men treated with cyproterone (100, 200 and 400 mg/d) for 8-14 days, serum LH remained within the normal range. It is concluded: 1) cyproterone, in very large doses, increases serum LH but not FSH levels in male rats; 2) the suppression of FSH produced by treatment of castrate rats with testosterone can be partially reversed by an antiandrogen, indicating that androgens may have at least a partial role in the feedback control of FSH in the male; 3) because very large doses of cyproterone were necessary to stimulate LH levels in the rat and pharmacologic amounts failed to produce changes in the human, it is unlikely that cyproterone will provide an effective LH reserve test in the male. {Endocrinology 90: 1655, 1972) C 1 is a potent antiandrogen which inhibits exogenous and endogenous androgenic effect at target tissues (1). The mechanism proposed for this inhibition is twofold: inhibition of the formation of a specific 5ct-dihydrotestosterone protein complex in target cells (2) and interference with the biogenesis of Cio steroids from C21 precursors (3). Cyproterone, unlike its acetylated derivative (cyproterone acetate) which is highly progestational, is neither progestational nor antiestrogenic (1,4). We felt that cyproterone, a pure antiandrogen, would be useful in investigations of the feedback control of gonadotropins in the male. Although it is generally agreed that testosterone is the major feedback regulator of LH secretion in the male, the exact mechanism for the control of FSH release is uncertain. Several studies have demonstrated that selective loss of spermatogenesis results in increased serum conReceived December 10, 1971. 1 Trivial names used: cyproterone (free alcohol) = l,2oc-methylene-6-chloro-V-pregnadiene-17ocol-3,20-dione; cyproterone acetate = l,2cc-methylene-6-chloro-V 4 • °-pregnadiene-17 oc -ol-3,20-dione-17 oc -acetate. centrations of FSH, suggesting that spermatogenesis is involved in the feedback regulation of FSH (5-7). However, it has shown that despite complete inhibition of spermatogenesis, serum FSH does not increase to levels as high as those seen in castrate animals (5, 8), indicating that in addition, testosterone or a testosterone metabolite may influence FSH regulation. If castrate rats are treated with sufficiently large doses of testosterone, both serum LH and FSH concentrations fall to intact levels (9,10). This effect of testosterone may represent either a direct androgenic influence or an indirect one mediated by the peripheral conversion of testosterone to estrogen. In this study, the effect of an antiandrogen on serum FSH levels was studied to clarify whether androgens can directly influence the feedback regulation of FSH. Studies were first performed to test the ability of cyproterone to increase serum concentrations of radioimmunoassayable LH and FSH in intact male rats. Both weanling and adult rats were used for these studies in order to evaluate whether the presence of mature spermatogenic tissue would influence the effect of cyproterone

Recent data indicate that the hypothalamus is capable of aromatizing androgens to estrogens; it has been suggested that this aromatization is required for hormonal activity at the hypothalamic level. In this study dihydrotestosterone and testosterone were administered over a broad dose range to castrate male rats. Dihydrotestosterone, an A-ring reduced steroid which is not convertible to estrogen, was demonstrated to be more potent than testosterone in suppressing serum LH levels while equipotent to testosterone in suppressing FSH. We conclude that conversion of androgens to estrogens is not required for inhibition of the hypothalamic-pituitary axis.

Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay in a group of elderly men following castration and oestrogen therapy. Prior to orchiectomy, mean serum concentrations of LH and FSH were within the normal range. Two days following castration, serum LH concentrations increased in all eight patients; higher levels of LH were subsequently measured in all but one patient after periods of time ranging from 49 to 210 days. Serum FSH levels, measured in three patients following castration, increased in a pattern parallel to LH changes. Ethinyl oestradiol (EOe) in doses ranging from 5 to 300 μg/day was administered to ten men who had been castrated 3 to 72 months earlier. Oestrogen treatment suppressed both LH and FSH in a parellel manner in nine of ten patients. LH was first suppressed to intact levels in one of eight patients treated with 20 μg/day of EOe, in two of six patients treated with 50 μg/day, and in one patient by 80 μg/day. FSH was not suppressed to precastration levels until 50 μg/day of EOe was administered; this dose suppressed three of six patients. Higher doses of EOe (150–300 μg/day) suppressed both LH and FSH to levels below the sensitivity of the assay. These data fail to demonstrate any differential effect of oestrogen on LH and FSH release.

Testicular tumors were studied by quinacrine hydrochloride fluorescence. All of them showed the presence of a Y chromosome. More tumors should be studied, paticularly testicular teratomas, to determine their origin.

In the immature castrate rat, the antiandrogens cyproterone (C) (30 or 150 mg⁄ kg) and cyproterone acetate (CA) (10 or 50 mg⁄kg) inhibited the growth of the ventral prostate and seminal vesicles that was induced by dehydroepiandrosterone (DHA), androstenedione (A), or testosterone (T) injected at various doses for 7 days. When the lowest doses of androgen were used (DHA 0.4 mg, A 0.02 mg, and T 0.015 mg), C and CA were often able to maintain the weights of target organs at castrate levels. CA was about 3 times more potent than C in antiandrogenic activity. CA also significantly inhibited the increase in prostatic weight that occurred after 14 days of administration of ACTH (20 U⁄day), prolactin (1 mg⁄day) plus ACTH (5 mg⁄day), or prolactin (1 mg⁄day) plus DHA (0.2 mg⁄day). It is concluded that C and CA can inhibit the known extratesticular stimuli to prostatic growth in the rat. These stimuli may all be mediated by an androgendependent cellular response. (Endocrinology 87: 624, 1970)

Renal toxicity of methylglucamine diatrizoate (Renografin-76) and sodium acetrizoate (Urokon-70) was tested in rats with experimentally induced acute tubular necrosis and hydronephrosis. Aortography performed with Renografin-76 (2.5, 7.5, and 12.5 mg/kg) produced no renal failure or mortality; yet, following aortography with Urokon-70 (2.5 ml/kg) , renal failure occurred in 60% with acute tubular necrosis and in 100% with hydronephrosis. The mortality rate in these two groups was 20 and 40%, respectively. Thus, intra-aortic injection of Renografin-76 in proportional doses far exceeding those used clinically caused no detectable renal toxicity, while known toxicity of sodium acetrizoate was confirmed.

The effects of cryptorchism on testis weight and histology, ventral prostate weight (VPW), and serum LH and FSH were assessed in rats 49 days of age. Rats 49 days of age have elevated FSH levels which fall to adult range when mature testis weight is achieved. Bilateral crytorchism producted: 1. histological changes in the testes by 3 days and a final reduction of testis weight of 75%; 2. a reduction of VPW of 40%; and 3. elevations of both serum LH and FSH by 4 days; serum FSH did not increase to castrate levels. It is concluded: 1. because serum FSH levels correlate with testicular maturation, some product of the germinal epithelium may selectively regulate FSH secretion; 2. because cryptorchism destroys the germinal epithelium but dose not elevate FSH to the castrate range, spermatogenic activity is not the sole regulator of FSH; and 3. because cryptorchism damages both the gametogenic and androgenic functions of the testes, it will not provide a model for studies of selective FSH regulation.

The poor prognosis associated with carcinoma in diverticula of the bladder is well documented. This case report demonstrates the rapid development of carcinoma in a diverticulum of the bladder within a four-month- period of observation, and suggests that early surgical excision is indicated.