Urinary FSH Excretion Research Articles

Consecutive Urinary Gonadotropin and Ovarian Hormone Excretory Patterns during LH-RH Analog Treatment in Female Patients with Central Precocious Puberty

To study the initial stimulative and subsequent suppressive effects of Luteinizing hormone releasing hormone analog (LHRH-a) therapy on the hypothalamic-pituitary-ovarian axis, serial urinary excretion of gonadotropin and ovarian steroids were investigated in 23 female patients with central precocious puberty. Among them, seven were treated with intranasal administration of buserelin (G1), seven with daily subcutaneous injection of buserelin (G2) and nine with subcutaneous injection of super-long-acting LHRH-a every 28 days (G3). After the initial therapy in G1, the levels of urinary gonadotropin excretion increased greatly with a high level persisting for a longer period. Responding to these increases, the levels of urinary total estrogen excretion increased to an excessively high maximum level. After the initial injection in G3, the levels of urinary gonadotropin and total estrogen excretion were augmented at the same time for a shorter period with a lesser excretion of urinary total estrogen. Ovarian cysts developed after urinary total estrogen attained a maximum and tended to grow depending on the duration and degree of high urinary total estrogen excretion.The size of ovarian cysts was greater in G1 than in G3. During therapy in all groups, the mean urinary gonadotropins were significantly suppressed compared with pretreatment. The mean urinary total estrogen excretory level during treatment in G1 was not significantly suppressed compared with before treatment, but on the other hand, with significant suppression in G3. During therapy, urinary FSH excretion increased within 24 hours of every injection of super-long-acting LHRH-a with a slight rise in LH only in all patients in G3 studied. Studies in many more patients are required because the number of subjects was limited in this study.

A Dose Finding Study of a Super Long-Acting Luteinizing Hormone-Releasing Hormone Analog (Leuprolide Acetate Depot, TAP-144-SR) in the Treatment of Central Precocious Puberty.

The effect of leuprolide acetate (D-Leu6-[des-Gly10-NH2]-LH-RH ethylamide acetate) for depot suspension (TAP-144-SR), a synthetic analog of luteinizing hormone-releasing hormone, was examined in three doses in 36 patients (34 girls, 2 boys) with central precocious puberty. TAP-144-SR was injected subcutaneously every four weeks for twelve weeks, and clinical symptoms and plasma and urinary levels of various hormones were followed every four weeks. Eleven girls given 10 micrograms/kg showed a significant decrease in peak plasma LH and FSH responses to LH-RH test, but basal plasma LH and FSH did not change significantly. In 13 patients (11 girls and 2 boys) given 30 micrograms/kg and 12 girls given 90 micrograms/kg, both basal and peak LH and FSH were significantly suppressed. Urinary excretion of LH decreased significantly in all groups except in the 10 micrograms/kg group. Urinary excretion of FSH did not change significantly in the 10 and 30 micrograms/kg groups, but it decreased significantly in the 90 micrograms/kg group. In girls, plasma and urinary estradiol also fell greatly, but the difference was insignificant except in the 90 micrograms/kg group. Regression of sexual characteristics was observed in almost half of the patients at the 12th week of the treatment. Side effects were minimal. A dose of more than 30 micrograms/kg of TAP-144-SR is effective in suppressing gonadotropins and causing improvement of clinical symptoms, and appears to be useful in treating children with central precocious puberty.

Quantitation of Urinary Gonadotropins in Normal Children

A simple and improved method for the quantification of urinary LH and FSH was developed. Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Urinary LH and FSH concentrated by ammonium sulfate were coeluted with an iodinated LH and FSH tracer. Gel chromatography of the urine revealed that the majority of immunoreactive LH and FSH were eluted coincident with 125I-LH and 125I-FSH. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Age-dependent changes in urinary LH excretion were significant in normal boys and girls 6-17 y of age. Urinary FSH excretion in these children did not change in an age-dependent fashion.

Follicle-stimulating hormone is required for quantitatively normal inhibin secretion in men.

Inhibin is a glycoprotein hormone produced by the testis and ovary which is postulated to be an important regulator of pituitary FSH secretion. Animal data indicate that inhibin is produced by the Sertoli cells of the testis under the influence of FSH. To determine the role of FSH withdrawal and replacement in the control of inhibin secretion in man, we measured serum inhibin concentrations in men in whom isolated FSH deficiency had been produced by chronic hCG administration; this was followed by FSH replacement. After a 3-month control period, four normal men received hCG for 7 months, resulting in suppression of serum FSH to undetectable levels and urinary FSH excretion to prepubertal levels. Their mean serum inhibin levels fell to 70% of control values during hCG administration [362 +/- 60 (+/- SE) vs. 518 +/- 56 U/L; P less than 0.01]. While continuing hCG, testosterone enanthate was administered for a further 6 months. Serum FSH and inhibin levels remained suppressed to a similar degree. Testosterone administration then was ceased, and hCG continued for a further 2-4 months. Then, while continuing hCG administration, FSH was replaced as either highly purified human FSH (n = 2) or human menopausal gonadotropin (n = 2) for a period of 4-10 months. Serum FSH levels increased to the mid- and upper normal male ranges, respectively. FSH replacement restored serum inhibin levels to 522 +/- 56 U/L (P = NS vs. control). In summary, prolonged selective FSH deficiency induced by chronic hCG administration suppressed inhibin secretion. Replacement of FSH activity restored inhibin secretion to control values. We conclude that 1) FSH is not absolutely required for inhibin secretion in men; and 2) the maintenance of quantitatively normal inhibin secretion requires the combined action of both gonadotropins.

Reproductive function during fasting in men.

To investigate reproductive function during fasting, six men 20-74% over ideal body weight completed an 18-day study consisting of a 3-day control period, a 10-day total fast, and a 5-day refeeding period. All men lost at least 4.1% of total weight and demonstrated ketonemia and ketonuria. The FSH response to LRH (0.2 microgram/min for 4 h) stimulation was significantly lower (P less than 0.05) during fasting and remained so during refeeding. Serum FSH concentrations were significantly lower (P less than 0.05) during the fast in five of six patients compared to those during the control period, whereas serum LH concentrations were unchanged. The effects of fasting on endogenous LH and FSH pulsations were studied by obtaining serum at 20-min intervals for 6 h on days 2, 11, and 16. Neither the amplitude nor the frequency of LH and FSH pulsations changed significantly during fasting or refeeding. Serum testosterone concentrations were significantly lower (P less than 0.025) by fasting day 9 compared to control values. The 24-h urinary excretion of both LH and FSH increased significantly (P less than 0.05) by fasting day 6 and reached a maximum by fasting day 8. Urinary LH excretion did not return to normal after 3 days of refeeding, whereas urinary FSH excretion returned to baseline by the first day of refeeding. We conclude that during short term fasting in obese men: 1) serum FSH concentrations decrease, 2) the pituitary responsiveness of FSH and LRH is blunted, 3) serum testosterone decreases, and 4) the urinary excretion of both LH and FSH increase.

Endocrinological studies in undescended testes.

A cross-sectional study was carried out on 168 boys aged 2.5-16.8 years with unilateral or bilateral testicular maldescent. Urinary excretion of testosterone, delta4-androstenedione, LH and FSH was investigated. The results were related to chronological age, bone age and sexual maturation stage. Urinary testosterone excretion was elevated in unilateral and bilateral cases of undescended testis under 9 years of age. The pubertal increase of testosterone excretion seemed to be moderately delayed in the patients. In pubertal stage V the testosterone excretion was normal. The mean testosterone/androstenedione relationship was normal in all age groups up to 14.9 years and increased in patients above this age. After HCG stimulation, the testosterone excretion increased at all ages studied whereas the androstenedione excretion increased only in bilateral cases under 11 years of age. Urinary LH excretion was diminished in bilateral cases aged 6.0-7.9 years and elevated in unilateral cases in pubertal stage V. Urinary FSH excretion was normal below 8 years of age, moderately elevated in bilateral cases aged 8.0-11.9 years and increased in unilateral cases in pubertal stage V. Patients with bilateral anorchia in pubertal stage I, had normal basal testosterone and androstenedione excretion while the LH and FSH levels were increased. The findings in this study indicated that disturbances in the pituitary-gonadal function of cryptorchids might be operative from early childhood and throughout pubertal years.

STUDIES ON SUSTAINED CONTRACEPTIVE EFFECTS WITH SUBCUTANEOUS POLYDIMETHYLSILOXANE IMPLANTS

ABSTRACT Ovarian function was assessed in 10 healthy young women, before and after the insertion of 3 or 4 polydimethylsiloxane capsules filled with 20 mg of megestrol acetate. Each capsule released in vitro, approximately 20 μg/24 h of the hormone. Daily determination of the urinary excretion of FSH, LH, fractionated oestrogens and pregnanediol were performed in all subjects during one control cycle, the first and the third cycle after the insertion of the capsules. Out of 10, 8 control cycles were ovulatory according to all the parameters investigated. This compares with 15 ovulatory cycles out of a total of 20, examined after the insertion of the capsules. During treatment no changes were observed in the FSH excretion pattern; the mid-cycle LH peak was present in all ovulatory cycles, although it was usually much less evident under the action of megestrol acetate. The excretion of oestradiol was significantly increased in all subjects (P < 0.05) during the first cycle following implantation. Oestrone and oestriol excretion was also generally higher in patients bearing PDS capsules; however, this difference was not statistically significant. Pregnanediol levels were not affected by the treatment in all cycles considered to be ovulatory on the basis of all the parameters. The menstrual bleeding pattern did not change in the majority of cases. One patient had, during treatment with 3 capsules, two profuse break-through bleedings whereas another one became amenorrhoic two months after the insertion of 4 implants. It is concluded that megestrol acetate sustained release preparations do not inhibit ovulation under the experimental conditions used.

Suppressed Follicle Stimulating Hormone in Men with Chorionic Gonadotropin Secreting Testicular Tumors

ABSTRACT Follicle stimulating hormone was measured in the plasma and urine prior to and after treatment in 7 men with testicular tumors secreting chorionic gonadotropin (CG). Plasma FSH was 2.5 ± 0.3 mIU/ml (se) when CG levels were elevated and 10.9 ± 2.1 mIU/ml following treatment when CG levels were normal. Urinary FSH was 0.08 ± 0.01 IU/24 hours when CG levels were elevated and 7.9 ± 1.2 IU/24 hours when CG had returned to normal. Comparable Comparable FSH concentrations in normal men determined in our laboratory are: plasma, 10.2 ± 0.8 mIU/ml, and urine, 5.5 ± 0.5 IU/24 hours. When CG was elevated, the urinary FSH excretion was lower than in any patient group heretofore described. The decreased FSH levels may be due to suppression by increased endogenous estrogen production or to hypothalamic feedback by CG.

Pituitary functions as judged by urinary excretion of FSH and LH in normal married young women cyclically treated with 0.5 mg megesterol acetate.

Using specific biological assay procedures FSH and LH excretion was measured in 2 normally menstruating young subjects before during and after administration of megesterol acetate from Days 5 to 25 of the cycle. Urinary excretion of total estrogen was also estimated. The laboratory data and the results of the preliminary clinical trial regarding the reproductive performance of the subjects are discussed.(FULL TEXT)

Effect of mestranol and chlormadinone acetate on urinary excretion of FSH and LH

Urinary excretion of FSH and LH was studied in normal ovulating women during 27 control cycles and during 37 cycles when various doses of mestranol and/or chlormadinone acetate were given singly, sequentially, or in combination. During the first cycle of treatment, the major effect of mestranol was a suppression of FSH excretion, with the effect diminishing as dosage levels were decreased from 100 to 80 to 60 μg per day. The effect on LH was definite but less consistent. Commencement of therapy on cycle day 1 was more suppressive than commencement on day 5. Repeated cyclic administration of mestranol suppressed both FSH and LH excretion. However, sporadic detectable levels of LH were seen occasionally even after 12 cycles of treatment. A dose of 10 μg mestranol per day had a stimulatory rather than a suppressive action on the excretion of both FSH and LH. Chlormadinone acetate at 2 mg. per day affected both FSH and LH excretion in rather unpredictable fashion. Simultaneous administration of chlormadinone acetate and mestranol appeared to have an additive effect.

URINARY FSH AND LH EXCRETION DURING THE NORMAL MENSTRUAL CYCLE

The urinary excretion of FSH and LH, as assayed by the ovarian weight augmentation and ovarian ascorbic acid depletion methods and compared with NIHFSH and LH ovine pituitary standards, was measured throughout 11 menstrual cycles in 5 normal female subjects. Daily vaginal smears were taken as an index of estrogen activity, and basal body temperatures were taken as an index of progesterone effect. There was a consistent pattern of FSH and LH excretion in all cycles studied. The excretion of FSH was highest during the menses and reached a low point at mid-cycle. Significant urinary LH activity was present only at mid-cycle. The greatest effect of estrogen on the vaginal smear occurred around mid-cycle and all subjects showed a rise in basal body temperature after the peak excretion of LH activity. The ratio of urinary FSH to LH activity varied significantly during the cycle.

URINARY FSH AND LH EXCRETION DURING THE NORMAL MENSTRUAL CYCLE.

The urinary excretion of FSH and LH, as assayed by the ovarian weight augmentation and ovarian ascorbic acid depletion methods and compared with NIHFSH and LH ovine pituitary standards, was measured throughout 11 menstrual cycles in 5 normal female subjects. Daily vaginal smears were taken as an index of estrogen activity, and basal body temperatures were taken as an index of progesterone effect. There was a consistent pattern of FSH and LH excretion in all cycles studied. The excretion of FSH was highest during the menses and reached a low point at mid-cycle. Significant urinary LH activity was present only at mid-cycle. The greatest effect of estrogen on the vaginal smear occurred around mid-cycle and all subjects showed a rise in basal body temperature after the peak excretion of LH activity. The ratio of urinary FSH to LH activity varied significantly during the cycle.

Gonadal dysgenesis with androgenic manifestations in the tall eunuchoid female.

Gordan et al. (1) recently reported a syndrome characterized by primary amenorrhea, lack of development of primary and secondary sexual characteristics, clitoridal hypertrophy, hirsutism, delayed skeletalmaturation, and short stature with webbing of the neck. Except for the hirsutism and the hypertrophy of the clitoris, the clinical picture resembled that of Turner's syndrome (2). Lack of sexual development withdecreased stature and high urinary fsh excretion due to primary ovarianagenesis has been described by Albright et al. (3), Varney et al. (4), andWilkina and Fleischmann (5). However, Albright et al. (3) also reported 2 patients with primary ovarian insufficiency who were not short in stature and whose urinary excretion of fsh was within normal limits.