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319. Spironolactone interference with androgen production in hirsute females
377
Abstracts
control group of 16 normal males belonging to the same age group and the same geographical area were T = 582 i_ and TB = 92.99 i 158 ng”,,. FSH = 15.09 k 8.74 mIU/ml. I.l4”,,, Student’s t test between groups showed no significant difference between the control group and any of the other groups studied (p < ,001). These results show that vasectomy in man does not cause detectable abnormality in testosteroneand FSH secretion and testosterone binding globulin synthesis even up to 5 years after operation. However, since a large variation was observed in the parameters studied among the individuals within each group. this investigation should be extended to study the concentration of these hormones in the ~amc individuals before and after vasectomy. * VRR is a student at the Patna Medical College, Patna. Bihar. India.
319. Spironolactone interference with androgen production in hirsute females RICCIARDI. 1.. DEL RIO, G. and IMPARATO, E.. Clinica Ostetrica e ginecologica delYUniversita di Pavia, Italia and II Cattedra di Anatomia Comparata dell’Universita di Napoli. Italia Spironolactonc (Aldactone) was given continuously in a dose of 200 mg/day p.0. to 5 hirsute females. The following hormonal studies were carried out prior to. and after 6 to 8 weeks of treatment (always in exactly the same phase of the menstrual cycle. whether spontaneous or progesteroneinduced), determination of plasma progesterone (P). 17hydroxyprogesterone (170HP), testosterone (T), androstenedione (A), dehydroepiandrosterone (DHA) and of urine testosterone and epitestosterone glucuronide (TG and EG). pregnanediol (Diol) and pregnanetriol (Triol), determination of the metabolic clearance rate (MCR) and production rate (PR) of T and A. Comparison of pre and post treatment shows: No significant variation of plasma P or urine Dial; a significant (P < 0.05) increase of plasma 170HP and of urine Trio1 in 4 out of 5 oatients; a significant (P < 0.05) decrease of plasma T and A and of urine TG and EG in 3 out of 5 patients; a significant decrease @ < 0.05) of plasma and urine DHA in 4 out of 5 patients; a significant (P < 0.01) decrease of PR or T and A, with slight or no variation of MCR. in 3 patients: The fall in PR for both steroids thus reflects the fall in plasma concentration. In view of the hormonal changes brought about by Spironolactone, the hypothesis is put forth that inhibition of desmolases is the basic mechanism involved. 320. Divergent dehydroepiandrosterone and dehydroepiandrosterone sulfate metabolism in obesity HALMY, L. and FEHER, T., First Department of Medicine, Otto Korvin Hospital, and First Department of Medicine, Semmelweis University Medical School, Budapest, Hungary and [7a3H]dehydroepi[4- “Cl Dehydroepiandrosterone androsterone sulfate were injected to obese female subjects, and the dynamic metabolism of the hormone pair was studied. Estimation of the rates of secretion, production and interconversion. determination of the metabolic clearance and the percentage appearance of metabolites in urine revealed sharp differences in metabolism of the two hormones, The secretion rate and volumes of distribution was greater. the irreversible metabolism of unconjugated dehydroepiandrosterone into urinary metabolites was less than
normal in obese subjects. In contrast. the secretion rate and production rate of dehydroepiandrosterone sulfate was normal, the volumes of distribution decreased and the metabolicclearancegreater than normal in obesity. Analysis of percentage appearance of urinary metabolites bearing [3H] isotope showed an accelerated metabolism of dehydroepiandrosterone sulfate into androsterone glucuronoside. A preponderance of dehydroepiandrosterone production and hindered interconversion to the sulfate suggested an uptake of dehydroepiandrosterone by a tissue of the outer compartment, and this may be the adipose tissue in obese female subjects studied. 321
Serum progesterone and uterine response following gonadotropin stimulation in normal and hyperthyroid rats DUBIN, N. H.. Department of Obstetrics and Gynaecology, University of Maryland. Baltimore, Maryland
The gonadotropin stimulated immature female rat served as a model to explore mechanisms of reproductive failure associated with hyperthyroidism. Rats received 30 i.u. PMS to stimulate ovulation and luteinization. In one group, hyperthyroidism was induced by injecting triiodothyronine (T,-Sng/day) beginning on day of PMS stimulation. In control rats. serum progesterone (SP) was elevated from 0,5ng/ml toapeakof226 ng/ml 10 daysafter PMS. By day 16, SP decreased to 28.6 ng/ml. SP was unaffected but uterine weight was 34”,, less (I, < ,001) in hyperthyroid rats compared to controls 8-14 days following PMS. Histologically. the myometrium but not the endometrium appeared less developedinuterifrom hyperthyroid versus normal rats. Pretreating rats with T, prior to PMS resulted in uterine ballooning 4 days after PMS while rats receiving PMS alone showed no ballooning. There was no difference in SP between these groups. The uterine response following PMS stimulation is modified by T, induced hyperthyroidism by a mechanism other than SP levels. (Supported by The Lalor Foundation). 322. Plasma hormone levels and adrenal responses in patients with prostatic disease undergoing anti-androgen therapy HARPER, M. E., COWLEY, T., BROWNSEY, B.. BOYNS. A. R. and PEELING, W. B., Tenovus Institute for Cancer Research, The Heath. Cardiff. Wales Although a large proportion of patients with prostatic cancer respond to antiandrogen therapy, many subsequently relapse. possibly due to a secondary production of adrenal androgens. Such patients have now been monitored regularly throughout their treatment with oestrogen. and plasma testosterone. androstenedione, cortisol, prolactin, LH and FSH measured. The role of the adrenal was studied using ACTH stimulation and dexamethasone depression tests. Comparison of results from controls, patients with benign prostatic hyperplasia and those with malignant disease, both untreated and treated, indicated that only in the oestrogen treated malignant group did ACTH increase plasma testosterone concentration. Dexamethasone similarly decreased testosterone levels. Oestrogen therapy significantly increased the prolactin levels in the plasma of these patients, and investigations in vitro suggest both a trophic effect of prolactin on the adrenal and an effect on testosterone uptake by the prostate in culture. In relation to this, the endocrine changes and clinical effects of CB154 (Sandoz Ltd.) treatment, a drug inhibiting prolactin release. have now been assessed.
Abstracts
control group of 16 normal males belonging to the same age group and the same geographical area were T = 582 i_ and TB = 92.99 i 158 ng”,,. FSH = 15.09 k 8.74 mIU/ml. I.l4”,,, Student’s t test between groups showed no significant difference between the control group and any of the other groups studied (p < ,001). These results show that vasectomy in man does not cause detectable abnormality in testosteroneand FSH secretion and testosterone binding globulin synthesis even up to 5 years after operation. However, since a large variation was observed in the parameters studied among the individuals within each group. this investigation should be extended to study the concentration of these hormones in the ~amc individuals before and after vasectomy. * VRR is a student at the Patna Medical College, Patna. Bihar. India.
319. Spironolactone interference with androgen production in hirsute females RICCIARDI. 1.. DEL RIO, G. and IMPARATO, E.. Clinica Ostetrica e ginecologica delYUniversita di Pavia, Italia and II Cattedra di Anatomia Comparata dell’Universita di Napoli. Italia Spironolactonc (Aldactone) was given continuously in a dose of 200 mg/day p.0. to 5 hirsute females. The following hormonal studies were carried out prior to. and after 6 to 8 weeks of treatment (always in exactly the same phase of the menstrual cycle. whether spontaneous or progesteroneinduced), determination of plasma progesterone (P). 17hydroxyprogesterone (170HP), testosterone (T), androstenedione (A), dehydroepiandrosterone (DHA) and of urine testosterone and epitestosterone glucuronide (TG and EG). pregnanediol (Diol) and pregnanetriol (Triol), determination of the metabolic clearance rate (MCR) and production rate (PR) of T and A. Comparison of pre and post treatment shows: No significant variation of plasma P or urine Dial; a significant (P < 0.05) increase of plasma 170HP and of urine Trio1 in 4 out of 5 oatients; a significant (P < 0.05) decrease of plasma T and A and of urine TG and EG in 3 out of 5 patients; a significant decrease @ < 0.05) of plasma and urine DHA in 4 out of 5 patients; a significant (P < 0.01) decrease of PR or T and A, with slight or no variation of MCR. in 3 patients: The fall in PR for both steroids thus reflects the fall in plasma concentration. In view of the hormonal changes brought about by Spironolactone, the hypothesis is put forth that inhibition of desmolases is the basic mechanism involved. 320. Divergent dehydroepiandrosterone and dehydroepiandrosterone sulfate metabolism in obesity HALMY, L. and FEHER, T., First Department of Medicine, Otto Korvin Hospital, and First Department of Medicine, Semmelweis University Medical School, Budapest, Hungary and [7a3H]dehydroepi[4- “Cl Dehydroepiandrosterone androsterone sulfate were injected to obese female subjects, and the dynamic metabolism of the hormone pair was studied. Estimation of the rates of secretion, production and interconversion. determination of the metabolic clearance and the percentage appearance of metabolites in urine revealed sharp differences in metabolism of the two hormones, The secretion rate and volumes of distribution was greater. the irreversible metabolism of unconjugated dehydroepiandrosterone into urinary metabolites was less than
normal in obese subjects. In contrast. the secretion rate and production rate of dehydroepiandrosterone sulfate was normal, the volumes of distribution decreased and the metabolicclearancegreater than normal in obesity. Analysis of percentage appearance of urinary metabolites bearing [3H] isotope showed an accelerated metabolism of dehydroepiandrosterone sulfate into androsterone glucuronoside. A preponderance of dehydroepiandrosterone production and hindered interconversion to the sulfate suggested an uptake of dehydroepiandrosterone by a tissue of the outer compartment, and this may be the adipose tissue in obese female subjects studied. 321
Serum progesterone and uterine response following gonadotropin stimulation in normal and hyperthyroid rats DUBIN, N. H.. Department of Obstetrics and Gynaecology, University of Maryland. Baltimore, Maryland
The gonadotropin stimulated immature female rat served as a model to explore mechanisms of reproductive failure associated with hyperthyroidism. Rats received 30 i.u. PMS to stimulate ovulation and luteinization. In one group, hyperthyroidism was induced by injecting triiodothyronine (T,-Sng/day) beginning on day of PMS stimulation. In control rats. serum progesterone (SP) was elevated from 0,5ng/ml toapeakof226 ng/ml 10 daysafter PMS. By day 16, SP decreased to 28.6 ng/ml. SP was unaffected but uterine weight was 34”,, less (I, < ,001) in hyperthyroid rats compared to controls 8-14 days following PMS. Histologically. the myometrium but not the endometrium appeared less developedinuterifrom hyperthyroid versus normal rats. Pretreating rats with T, prior to PMS resulted in uterine ballooning 4 days after PMS while rats receiving PMS alone showed no ballooning. There was no difference in SP between these groups. The uterine response following PMS stimulation is modified by T, induced hyperthyroidism by a mechanism other than SP levels. (Supported by The Lalor Foundation). 322. Plasma hormone levels and adrenal responses in patients with prostatic disease undergoing anti-androgen therapy HARPER, M. E., COWLEY, T., BROWNSEY, B.. BOYNS. A. R. and PEELING, W. B., Tenovus Institute for Cancer Research, The Heath. Cardiff. Wales Although a large proportion of patients with prostatic cancer respond to antiandrogen therapy, many subsequently relapse. possibly due to a secondary production of adrenal androgens. Such patients have now been monitored regularly throughout their treatment with oestrogen. and plasma testosterone. androstenedione, cortisol, prolactin, LH and FSH measured. The role of the adrenal was studied using ACTH stimulation and dexamethasone depression tests. Comparison of results from controls, patients with benign prostatic hyperplasia and those with malignant disease, both untreated and treated, indicated that only in the oestrogen treated malignant group did ACTH increase plasma testosterone concentration. Dexamethasone similarly decreased testosterone levels. Oestrogen therapy significantly increased the prolactin levels in the plasma of these patients, and investigations in vitro suggest both a trophic effect of prolactin on the adrenal and an effect on testosterone uptake by the prostate in culture. In relation to this, the endocrine changes and clinical effects of CB154 (Sandoz Ltd.) treatment, a drug inhibiting prolactin release. have now been assessed.