Gonadotropin Excretion Research Articles

Two cases of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) associated with hGH deficiency and marginal impairment of other hypothalamic‐pituitary functions

Plasma hGH response to provocative tests (insulin-induced hypoglycaemia and arginine infusion) appears normal in Turner's syndrome. Two cases are reported of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) with unusual absence of plasms hGH response to provocative tests (arginine infusion, insulin-induced hypoglycaemia). Study of other pituitary functions supports the view that a hypothalamic-pituitary impairment is present in these cases. In fact, in these cases we observed low values of gonadotrophin excretion and limited responses of plasma ACTH and plasma corticosteroids to provocative tests (insulin-induced hypoglycaemia, metopyrone). Moreover, markedly abnormal plasma TSH response to TRF was observed in Case 2. The results are discussed with reference to the significance of this rare association.

THE EFFECTS OF LARGE DOSES OF THE ANABOLIC STEROID, METHANDROSTENOLONE, ON AN ATHLETE

Doses of the anabolic steroid, methandrostenolone, nearly ten times greater than those used therapeutically, have resulted in a marked depression of levels of testosterone in urine and blood, and in some depression of gonadotrophin excretion by a male athlete. The administration of the drug has been checked and its metabolism studied from the pattern of urinary metabolites.

A new method simplifying collection of serial specimens for gonadotropin determinations.

Patterns of gonadotropin levels have been compared in specimens of serum, 24-h urine collections, and first morning urine voidings collected throughout a menstrual cycle from 8 sexually mature, young women. Quantities of gonadotropins in first morning voidings were found to provide a reliable estimate of 24-h excretion of these hormones and demonstrate the same patterns of change as do serum and 24-h urine specimens. Thus first morning voidings satisfactorily overcome logistical problems inherent is serial serum and 24-h urine sampling for studying gonadotropin excretion patterns.

Gonadotropin excretion in response to audiostimulation of human subjects

The effects of intermittent periodic sound stimuli on LH excretion and TGA by normal subjects and by two patients with low gonadotropin output were studied.

THE RELATIONSHIP BETWEEN MENOPAUSAL VASOMOTOR SYMPTOMS AND GONADOTROPHIN EXCRETION IN URINE AFTER OOPHORECTOMY

Summary The prevalence of menopausal vasomotor symptoms was assessed in 190 women seen for the first time at various intervals after oophorectomy. Urinary gonadotrophin excretion was measured and the vasomotor symptoms were assessed in 119 patients who were seen again at least one year after being given prescriptions for two tablets daily of either 20 μg. of mestranol or placebo. The prevalence of symptoms decreased with the elapse of time after oophorectomy and showed a significant inverse correlation with urinary gonadotrophin excretion. Mestranol therapy caused a significant reduction in both the prevalence of symptoms and urinary gonadotrophin excretion. Therapeutic failures were usually the result of inadequate medication. It is suggested that menopausal vasomotor symptoms and gonadotrophin excess both reflect hypothalamic-pituitary dysfunction and are not otherwise causally related.

Diagnosis and therapy of anorchism.

Clinical and hormonal findings and the results of therapy in 10 cases of anorchism are presented. Anorchism might be suspected on the basis of the following symptoms: lack of testicles and puberty, increased excretion of gonadotropins and decreased excretion of 11-deoxy-17-ketosteroids. The final diagnosis can only be established by laparotomy which would prove the absence of the testicles. If therapy was started before puberty or at the usual age of puberty, normal body proportions and full masculinization could be achieved; if, however, therapy was started at a later age, only full masculinization could be achieved.

PREMATURE OVARIAN FAILURE

Twenty-six patients with premature ovarian failure (last menstrual period before the age of 30 years) were evaluated clinically and endocrinologically and, in addition, ovarian biopsies were obtained in 15 out of the 26 patients. Only 1 of the patients revealed a family history of early menopause. The typical menstrual pattern indicated a normal age at menarche with regular periods for various length of time followed either by amenorrhoea abruptly or by a period of oligomenorrhoea before the onset of amenorrhoea. All patients showed normal or slightly underdeveloped secondary sexual characteristics, and it should be noted that 2 patients had been pregnant previously.It was characteristic of all patients that the excretion of total gonadotropins was constantly increased and that the excretion of total oestrogens was low, whereas both the adrenal and thyroid function were normal. All patients were X-chromatin positive.In 13 out of the 15 patients, in whom ovarian biopsies were obtained, the histological exa...

LH-RH test in 100 patients with ovarian insufficiency.

ABSTRACT The effect of synthetic LH-RH was studied in 100 patients with various types of ovarian insufficiency by following up the FSH- and LH-levels in plasma. LH-RH was administered in doses of 12.5, 25 and 100 μg as a rapid intravenous injection. The patients were classified according to the endocrine state of the pituitary as evidenced by the urinary gonadotrophin levels. A clear correlation between the functional state of the pituitary and its responsiveness to exogenous LH-RH was demonstrated. Most of the patients with undetectable low urinary gonadotrophin levels failed to respond. The majority of patients with gonadotrophin excretion in the normal range and those with elevated levels reacted with a dose dependent increase in circulating LH. The amount of liberated FSH however was related to the injected dose only in patients with high gonadotrophic excretion. The present study indicates that synthetic LH-RH provides a useful tool in the evaluation of the pitutiary function particularly in patients with low and with undetectable gonadotrophin excretion. The data presented in this paper also demonstrate that the functional state of the pituitary is clearly reflected by the urinary gonadotrophin levels.

Endocrinological aspects of male infertility.

Abstract. In order to clarify to what extent a hormonal disturbance may cause infertility in men, a study was made of 98 infertile men aged 23–52 years. Their spermatogenesis was defective. Urinary excretion of total gonadotropins, LH, estrogens, 17‐ketogenic steroids, 17‐ketosteroids and fractionated 17‐ketosteroids was determined. The patient material was divided into 4 groups according to the excretion of total gonadotropins and estrogens in the urine. The groups were compared with a control group of 50 healthy males (aged 16–47 years) of proven fertility.Group I had an elevated excretion of total gonadotropins and estrogens in the urine. No treatment was possible in this group. In group II, the excretion of total gonadotropins was <40 MU/litre, the excretion of LH was slightly elevated and the excretion of estrogens in the urine was higher than in the control group. A faulty testicular response to normal gonadotropin stimulation or an imbalance in the FSH/LH ratio might explain the increased estrogen excretion in the urine. In group III, the excretion of total gonadotropins and estrogens in the urine was normal and the excretion of 17‐ketogenic steroids was slightly diminished.In group IV, there was a decreased excretion of steroids in the urine, which may support the diagnosis of pituitary hypofunction. This group is the only one in which treatment with gonadotropins might prove successful. The excretion of DHA was low in groups I and IV, probably depending on the condition of the germinal epithelium.The conclusion is reached that the cause of infertility in males may occasionally be a hormonal disturbance depending on hypothalamus‐pituitary hypofunction. Only men who have a low excretion of gonadotropins and steroids in the urine may have a chance of becoming fertile after treatment with gonadotropic or releasing hormones.

SUPPRESSION OF URINARY AND PLASMA FOLLICLE STIMULATING HORMONE BY EXOGENOUS ESTROGENS IN PREPUBERTAL AND PUBERTAL CHILDREN

Clomiphene citrate, an anti-estrogen with mild estrogenic properties, inhibits rather than stimulates gonadotropin excretion in prepubertal and early pubertal children. These and other data suggest that the sensitivity of the hypothalamic-pituitary gonadostat decreases at the onset of puberty. To test this hypothesis further, the daily excretion of urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was determined in 19 children (5 short normals and 14 with isolated human growth hormone (HGH) deficiency) who were given ethinyl estradiol (EE) 1.4-14.7 mug/m(2) per day (2-10 mug/day) for 4 to 7 days. In addition, plasma and urinary gonadotropins and plasma estrogens were serially determined in two prepubertal females(with isolated HGH deficiency) given two injections (24 h apart) of estradiol benzoate, 10 mug/kg. FSH and LH concentrations in plasma and kaolin-acetone urinary concentrates and plasma 17beta-estradiol (E(2)) and estrone (E(1)) were measured by radioimmunoassays. 2-3 mug/m(2) per day of EE significantly suppressed urinary FSH (and LH when detected in the control period) in two out of six prepubertal children, while all doses >5 mug/m(2) per day suppressed urinary gonadotropins to undetectable levels in eight prepubertal subjects. In early to midpubertal subjects. 2-10 mug/m(2) per day of EE produced a slight suppression of urinary FSH, but failed to suppress to undetectable levels. Two subjects in late puberty (stage 4) did not suppress their urinary FSH while on 7 and 8.3 mug/m(2) per day. In both subjects treated with estradiol benzoate, plasma FSH promptly decreased after the first injection. Urinary FSH was suppressed to <0.1 IU/day on day 2 and urinary and plasma gonadotropins remained suppressed for the duration of the study (3 days). Plasma E(2) and E(1) rose from prepubertal values to peak concentrations of 150 to 250 pg/ml (E(2)), and 50 and 100 pg/ml (E(1)) at approximately 36 h. We conclude that the hypothalamic-pituitary-gonadal axis is operative in the prepubertal child and that the sensitivity of the hypothalamic-pituitary center(s) which control the secretion of FSH and LH decreases at the onset of puberty in man.

Urinary gonadotrophins following castration of men.

ABSTRACT The excretion of total hypophyseal gonadotrophins (HG), follicle stimulating hormone (FSH) and luteinizing hormone (LH) was studied in 13 castrated men aged 23 to 56 years, mean 38.8 years. All the men were castrated for legal reasons. The time from castration to the investigation varied from 4 weeks to 24 years. Four of the subjects were studied from the time before surgery until 4 weeks after castration. The mean excretion of HG, FSH and LH was statistically significantly higher than that of normal men of the same age i. e. by 8, 9 and 3 times higher respectively. The FSH/LH ratio was in the mean 2.8. Following orchiectomy FSH rose more rapidly and to a higher level than LH. The maximal level of FSH was reached within 1–2 weeks after castration in contrast to LH which did not consistently reach the maximal level within 4 weeks. This difference in FSH and LH levels after castration supports the concept that FSH and LH are regulated independently in man.

Fetal androgen and human chorionic gonadotropin excretion in relation to genetic sex

nancies involving the distal portion of the isthmus or those of the ampulla, it appears to be a relatively easy procedure. It is probable that ex:ensive coagulation of the tube without excision would result in the eventual resorption of the ectopic: gestation. This would avoid the possibility of bleeding secondary to excision. Laparoscopic excision would be contraindicated in those patients where preservation of tubal function is necessary. In such cases, linear salpingostomy would be the procedure of choice. In patients with numerous adhesions from previous pelvic infection, tubal excision would be foolhardy. Obvious advantages of this procedure are its decreased operative morbidity, absence of a surgical scar, shorter hospital stay, and substantially lower cost to the patient.

QUANTIFICATION OF HUMAN SEMINIFEROUS EPITHELIUM

Fortyfour infertile 46,XY men with severe deficiencies of the spermiogram were investigated by quantitative analyses of the seminiferous epithelium, employing the Sertoli cell number as a basis for reference. The following five groups of germ cells were recorded separately: 1) Spermatogonia, 2) preleptotene + leptotene spermatocytes, 3) zygotene + pachytene spermatocytes, 4) Sa + Sb spermatids and 5) Sc + Sd spermatids. The results were compared with previous results from similar studies in controls. Four of the patients had normal or only slightly impaired spermatogenesis, while the rest showed substantial abnormalities. In 21 cases an isolated reduction in the number of late or both early and late spermatids was found. In six other patients also the number of spermatogonia and/or spermatocytes was reduced. The remaining 13 cases showed heterogeneous pictures, composed of Sertoli cell‐only tubules, tubules with germ cells and partly or totally obliterated tubules. Males with different types of testicular lesions often showed the same degree of oligospermia. Although several of the patients showed abnormal features that may interfere with fertility, it was not possible to correlate failure of the testicle to descend, varicocele, abnormal hair distribution or abnormal excretion of 17‐ketosteroid fractions to any characteristic trait in the seminiferous epithelium. The urinary excretion of total gonadotrophins was within normal limits in all but two of the cases. Only six of the patients had small sized testes.

Effects of antibodies to luteinizing hormone-releasing hormone in the male rabbit and on the rat oestrous cycle.

3 male and 2 female rabbits were immunized with synthetic luteinizing hormone - releasing hormone (LH-RH) conjugated to bovine serum albumin. 4 weeks later at autopsy marked involution of the seminiferous tubules was seen in the males. Spermatogenesis was unobserved. The female animals were kept alive as a source of antibody; thus no information on their gonads was available. By testing serum from the immunized animals for its capacity to bind radioiodinated LH-RH it was determined that the rats had produced antibody. The antibody had inactivated endogenous LH-RH and consequently reduced pituitary gonadotrophin excretion. Experiments in which the antisera from these animals was injected intravenously into normal adult females indicated that LH-RH is necessary for the events leading to the proestrus state before the second day of diestrus. Rats injected with antiserum before 1430 hours on the day of proestrus had no ovulation and showed uterine distension the clearest evidence at writing of the article that LH-RH is necessary for the hormonal stimulus leading to ovulation.

Detailed hormonal studies during and after pregnancy in a previously hypophysectomized patient.

ABSTRACT This is a report on detailed hormonal studies before, during, and after pregnancy in a hypophysectomized patient who conceived after treatment with human gonadotrophins. On the basis of the results the following conclusions were drawn: In a patient who, judging by numerous investigations, no longer had any production of pituitary gonadotrophic hormones, it was possible by treatment with human gonadotrophic hormones to induce ovulation, without further stimulation to attain conception and preserve the conceptus, to carry through a normal pregnancy, ending at term in vaginal delivery of a normal infant. In this patient, whose pituitary corticotrophin production had totally ceased or had been negligible before the pregnancy, the endocrine state appeared to be completely normalized during pregnancy; thus: on unchanged corticosteroid medication the mean plasma corticoid concentration as well as the urinary excretion of corticoid metabolites, 17-ketogenic steroids, and 17-ketosteroids were considerably higher during than after the pregnancy, the urinary excretion of pregnanediol, oestriol and chorionic gonadotrophin was normal during the pregnancy. Moreover, the results of metyrapone tests before, during and after the pregnancy, ACTH stimulation test after delivery, and measurements of diurnal fluctuations in the concentration of plasma cortisol during the pregnancy are reported. The increased steroid production during pregnancy may be partially explained as a consequence of the activity in the foeto-placental unit which, however, can hardly have been quantitatively decisive. It must be presumed, therefore, that as a result of the pregnancy ACTH or an ACTH-like factor has been secreted, stimulating the maternal adrenal. It is assumed that the corticotrophin has been produced in the placenta and that it has passed to the maternal circulation.

Suppression of urinary and plasma follicle-stimulating hormone by exogenous estrogens in prepubertal and pubertal children.

Clomiphene citrate, an "anti-estrogen" with mild estrogenic properties, inhibits rather than stimulates gonadotropin excretion in prepubertal and early pubertal children. These and other data suggest that the sensitivity of the hypothalamic-pituitary "gonadostat" decreases at the onset of puberty. To test this hypothesis further, the daily excretion of urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was determined in 19 children (5 "short normals" and 14 with isolated human growth hormone (HGH) deficiency) who were given ethinyl estradiol (EE) 1.4-14.7 mug/m(2) per day (2-10 mug/day) for 4 to 7 days. In addition, plasma and urinary gonadotropins and plasma estrogens were serially determined in two prepubertal females(with isolated HGH deficiency) given two injections (24 h apart) of estradiol benzoate, 10 mug/kg. FSH and LH concentrations in plasma and kaolin-acetone urinary concentrates and plasma 17beta-estradiol (E(2)) and estrone (E(1)) were measured by radioimmunoassays. 2-3 mug/m(2) per day of EE significantly suppressed urinary FSH (and LH when detected in the control period) in two out of six prepubertal children, while all doses >5 mug/m(2) per day suppressed urinary gonadotropins to undetectable levels in eight prepubertal subjects. In early to midpubertal subjects. 2-10 mug/m(2) per day of EE produced a slight suppression of urinary FSH, but failed to suppress to undetectable levels. Two subjects in late puberty (stage 4) did not suppress their urinary FSH while on 7 and 8.3 mug/m(2) per day. In both subjects treated with estradiol benzoate, plasma FSH promptly decreased after the first injection. Urinary FSH was suppressed to <0.1 IU/day on day 2 and urinary and plasma gonadotropins remained suppressed for the duration of the study (3 days). Plasma E(2) and E(1) rose from prepubertal values to peak concentrations of 150 to 250 pg/ml (E(2)), and 50 and 100 pg/ml (E(1)) at approximately 36 h. We conclude that the hypothalamic-pituitary-gonadal axis is operative in the prepubertal child and that the sensitivity of the hypothalamic-pituitary center(s) which control the secretion of FSH and LH decreases at the onset of puberty in man.

Pituitary gonadotrophins and 17-ketosteroids in patients with the XYY syndrome.

ABSTRACT The urinary excretion of pituitary gonadotrophins and 17-ketosteroids was studied in nine males with karyotype 47,XYY and the serum testosterone in five such patients. We found a comparatively low urinary excretion of pituitary gonadotrophins as well as of dehydroepiandrosterone. The conclusion of the study combined with previous results is, however, that there are no indications of any pronounced abnormality in the urinary excretion of pituitary gonadotrophins or 17-ketosteroids and normal concentrations of serum testosterone in males with the XYY syndrome, in spite of the abnormality of the testis found in a high proportion of such patients.

Premature Ovarian Failure

Abstract. Twenty‐six patients with premature ovarian failure (last menstrual period before the age of 30 years) were evaluated clinically and endocrinologically and, in addition, ovarian biopsies were obtained in 15 out of the 26 patients. Only 1 of the patients revealed a family history of early menopause. The typical menstrual pattern indicated a normal age at menarche with regular periods for various length of time followed either by amenorrhoea abruptly or by a period of oligomenorrhoea before the onset of amenorrhoea. All patients showed normal or slightly underdeveloped secondary sexual characteristics, and it should be noted that 2 patients had been pregnant previously.It was characteristic of all patients that the excretion of total gonadotropins was constantly increased and that the excretion of total oestrogens was low, whereas both the adrenal and thyroid function were normal. All patients were X‐chromatin positive.In 13 out of the 15 patients, in whom ovarian biopsies were obtained, the histological examination revealed a normal stroma without or with very few primordial and atretic follicles, a picture very similar to that characteristic of the postmenopausal ovary. In the last 2 patients, however, the histological examination showed a quite different picture, viz. a normal stroma with numerous primordial and primary follicles and even a few growing follicles. In spite of these morphologically normal follicles, it was not possible to stimulate the follicular development and to induce ovulation even with very high doses of human gonadotrophins. It is, therefore, concluded that the presence of a few growing follicles in the ovaries does not seem to exclude the diagnosis of premature ovarian failure.Only 14 out of the 26 patients had the typical symptoms of the climacteric, and even in these cases the nuisance was only of a mild to moderate degree. It is generally agreed that all patients with symptoms should receive substitution therapy, but the essential risk of ischaemic heart disease and osteoporosis, together with the unquestionable psychological effect of having regular menstrual bleeding, have led us to the conclusion that this therapy is indicated in all cases of premature ovarian failure. Cyclical treatment either with a sequential preparation or with oestrogens alone is the treatment of choice.

Disorders of growth hormone and corticotropin regulation in patients with empty sella.

✓ Endocrine functions in seven cases of primary empty sella were studied. No clinical features of endocrine disturbances were apparent. Urinary excretion of gonadotropins, and thyroid and adrenal functions were normal. Plasma human growth hormone (HGH) concentration was also normal but did not increase after insulin-induced hypoglycemia in four patients, after arginine in one, and after a glucose load in six. Urinary excretion of 17-hydroxycorticosteroids (17-OHCS) increased normally in all patients after metyrapone administration, while plasma 17-OHCS did not increase in three subjects after insulin-induced hypoglycemia or in one after lysine-vasopressin. Two patients showed exaggerated responses to lysine-vasopressin. These results indicate an impairment of the hypothalamic HGH and corticotropin regulation in patients with empty sella. Since in chromophobe adenomas comparable changes were seen, the differential diagnosis between empty sella and chromophobe adenoma is impossible on the basis of endocrinological data alone. The only reliable diagnostic method is accurate radiological study including air contrast tomoencephalography.

New Observations on the Excretion of Chorionic Gonadotrophin During Pregnancy in the Rhesus Monkey (Macaca mulatta)

Small amounts of chorionic gonadotrophin (CG) were excreted throughout pregnancy by a rhesus monkey. Peak excretion of monkey chorionic gonadotrophin (MCG) occurred 25-28 days after the first day of mating. Urines collected post partum did not contain a measurable amount of gonadotrophin. The concentration of MCG in the placenta per g wet weight of tissue was equivalent to 6.3 1U human chorionic gonadotrophin (HCG).