FSH Excretion Research Articles

Profound reduction of ovarian estrogen by aromatase inhibition in obese women

It was hypothesized that aromatase inhibitor (AI)-induced interruption of estradiol negative feedback would modulate the reproductive hormone profile of obese women. Regularly cycling women aged 18-40 years with a BMI of 18-25 kg/m(2) (normal weight, n = 10) or >30 kg/m(2) (obese; n = 12) were given AI daily for 7 days. Urinary hormone profiles were compared between groups. Fourteen eumenorrheic, normal weight women not receiving AI stimulation served as historical controls. Urinary metabolites for LH, FSH, estradiol (E1c), and progesterone (Pdg) were measured and normalized to a 28-day cycle. Serum estrone and estradiol were measured in the late follicular phase. Whole-cycle LH, FSH, and luteal Pdg excretion did not differ between obese (BMI = 37.1 + 7 kg/m(2) ) and normal weight women treated with AIs, although LH was greater in stimulated compared with unstimulated normal weight women. Whole cycle mean E1c was lower in AI-stimulated obese and normal weight participants compared with nonstimulated normal weight controls, but obese women treated with AI excreted far less E1c (467.7 ± 217.4 μg/mg Cr) than AI-treated normal weight women (911.4 ± 361.8 μg/mg Cr; P = 0.02). Follicular phase serum estrone and estradiol were also lower in AI-treated obese women versus AI-treated normal weight women (61.7 ± 22.8 and 18.3 ± 3.7 pg/ml versus 99.1 ± 30.5 and 37.7 ± 5.9 pg/ml, respectively; P = 0.034 and 0.005). Normal gonadotropin output and luteal function occur at the expense of reduced E1c excretion in AI-treated women, and this discrepancy is particularly evident in obese women.

The effect of alpha-difluromethylornithine and tartaric acid on sperm count, seminal gamma GT, FSH, LH, testosterone and steroid excretion in patients with chronic prostatitis.

The inactivation of ornithine decarboxylase, a polyamine biosynthetic enzyme, by alpha-difluoromethylornithine (alpha-DFMO) was studied in patients with chronic non-suppurative prostatitis. Partial clinical response and remission of gross hematospermia were observed after 18 g/day alpha-DFMO, when administered orally for 1 month. The determination of gamma-glutamyltransferase, LH, Testosterone in semen and also of sperm motility and vitality appeared distinctly changed in alpha-DFMO treated patients, indicating a significant effect on the activity of the prostate. -- A 16% decrease of hematocrit and hemoglobin in 2 out of 10 patients was reversible 2 months after stopping the therapy. The placebo, which was identified mainly as tartaric acid after termination of the study showed similar clinical response and change of seminal parameters. The modulation of sperm count, seminal gamma GT, LH and testosterone was correlated to the known inhibition of prostatic acid phosphatase by tartaric acid in vitro.

Pseudohypogonadism: defective masculinization in a subject with normal FSH, ICSH and testosterone secretion.

A 19-year old male is presented with clinical signs of hypoandrogenism but normal excretion of FSH, ICSH and testosterone. In addition, the Clomiphene stimulation test had revealed a normal hormonal reserve. Cariotypes taken from blood and skin ruled out mosaicism as a possible cause. These findings and the absence of response to exogenous testosterone suggested peripheral resistance to androgen. The name "pseudo-hypogonadism" is again suggested for this rare condition in which defective masculinization is at variance with the hormonal studies which are normal.

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes. Cross-sectional study. In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined. Basal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibull lambda analysis. There was no difference between approximate entropy ratios or Weibull gamma analyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution. In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone functional changes.

Onset of Ovulation after Menarche in Girls: A Longitudinal Study

Hypothalamic-pituitary axis maturity has been believed to be the rate-limiting step in the development of ovulatory menstrual cycles. We hypothesized that, given current nutritional conditions, hypothalamic-pituitary axis maturation would be relatively rapid in menarcheal girls. Daily urine and menstrual records were collected for 2 yr each from 10 girls aged 11-13 yr at study entry. Urinary excretion of LH, FSH, estradiol (E1c), and progesterone (Pdg) metabolites was measured using established ELISAs. An objective algorithm detected rises of LH, FSH, E1c, and Pdg consistent with follicular maturation and/or ovulation. Nine of 10 girls enrolled into the study experienced the onset of menarche prior to or during the 2-yr collection period. LH and FSH surges, as well as small amplitude Pdg increments, were observed prior to menarche. Regular, ovulatory-appearing cycles with LH surges and gradually increasing and more sustained Pdg rises were observed over time after menarche, although duration of Pdg elevations remained shorter than in adult women (8.9 +/- 1.0 vs. 12.1 +/- 0.8 d, P = 0.043). E1c levels leading to LH/FSH surges were lower in perimenarcheal girls than adult controls, and bleeding episodes did not uniformly correlate with hormone patterns. Progressive increases in FSH and Pdg, but not LH or E1c, were observed in association with menarche. Mature hormone patterns are established within several months of and even prior to menarche in normal-weight perimenarcheal girls. Factors determining menstrual bleeding in perimenarcheal girls may not be solely dependent on reproductive hormones or the neuroendocrine axis.

Pituitary-Gonadal Function in Adolescent Males Born Appropriate or Small for Gestational Age with or without Intrauterine Growth Restriction

Being born small for gestational age (SGA) is suggested to influence female pituitary-gonadal axis, but only a few studies have focused on male pituitary-gonadal function. Our objective was to evaluate the influence of fetal growth rate on male reproductive function. We conducted a follow-up study of a prospective study with data on third trimester fetal growth velocity and birth weight. The study was conducted at Copenhagen University Hospital. Fifty-two healthy adolescent males participated. They were divided into those born appropriate for gestational age (AGA) and SGA, with or without intrauterine growth restriction. Pubertal stage, testicular size, and reproductive hormones were determined. Overnight 20-min LH and FSH profiles and overnight urine LH and FSH were determined in an additional study (n=30). No significant differences were found in testosterone levels (19.2 vs. 18.9 nmol/liter), inhibin B levels (186.5 vs. 188.0 pg/ml), or LH/testosterone ratio (0.15 vs. 0.18) between AGA and SGA, respectively. No significant differences in overnight secretory patterns of gonadotropins or testicular size and morphology were determined by ultrasonography between AGA and SGA. Fetal growth velocity did not influence any of the reproductive hormone levels. Overnight urinary LH and FSH excretion correlated statistically significantly with overnight LH (r=0.50; P=0.02) and FSH (r=0.44; P=0.04) secretion, respectively. Poor third trimester growth and/or low birth weight had no effect on subsequent male reproductive hormones. Contrasting a previous study, we found no difference in testosterone or inhibin B levels between SGA and AGA, suggesting that testicular function was not impaired in adolescent males born after compromised fetal growth.

Modulation of estrous cycle and LH, FSH and melatonin levels by pinealectomy and sham-pinealectomy in female rats

1. 1. The pineal has been shown to have a role in controlling reproduction of polyestrus mammals (like humans and laboratory rodents). It influences the age of sexual maturation; the timing of the ovulatpry cycle; and gonadal steroidogenesis. 2. 2. Here the authors report the early and late effects of pinealectomy (Px) and sham-pinealectomy (SPx) on the estrous cycle periodicity, plasma LH, FSH and urinary 6-sulphatoxymelatonin (6-SMT) excretion in female rats. 3. 3. Female Wistar rats (3–4 months of age) were maintained on 12/12 L/D cycle. Orbital venous plexus blood and urine samples were collected from the same rat during the estrus phase before surgery, 4–7 and 55–60 days post surgery. 4. 4. Daily vaginal smears were taken to monitor the estrous cycle and they showed a time dependent increase in the estrus stage duration in Px rats (estrus stage: 1 day in control; 3–4 days after 45 days Px). 5. 5. The decrease of gonadotropins at early post Px was due to surgical stress. 6. 6. 6-SMT levels were significantly lower at 4–7 days post SPx, but at 55–60d post surgery these levels returned to control values, which indicate pineal gland integrity. The reduction in urinary 6-SMT may be attributed to a possible high level of plasma corticosterone occurring after surgical manipulations. 7. 7. 6-SMT levels in Px rats were extremely lower at 4–7 and 55–60 days post surgery, but not null, confirming the surgical removal of the pineal gland and indicating the synthesis of melatonin in sites other than the pineal gland.

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.

Characterization of reproductive hormonal dynamics in the perimenopause.

Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.

Exercise Induces Two Types of Human Luteal Dysfunction

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.

Exercise Induces Two Types of Human Luteal Dysfunction: Confirmation by Urinary Free Progesterone*

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.

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.

The approach of menopause: A New Zealand study

Once weekly observations of the excretion of FSH, LH, oestrogens and pregnanediol have been used to monitor the changes which occur as New Zealand women approach and pass through the menopause. There were 3 patterns of hormone excretion. (1) Premenopausal women (aged 40-51 yr) had regular menstrual cyclicity with hormone patterns similar to those seen in the ovulatory cycles of fertile young women. (2) Women in the menopausal transition (40-55 yr) had irregular menstrual cyclicity with erratic hormone fluctuations. There were ovulatory cycles, postmenopausal episodes in which amenorrhoea was associated with high gonadotrophin levels and low urinary oestrogens, and times when the excretion of both gonadotrophins and oestrogens soared. Ovarian activity did not cease at the menopause, and postmenopausal women in the 6 months following final menstruation (44-55 yr) had hormone patterns which were indistinguishable from those observed in the long anovulatory cycles of the menopausal transition. (3) Older women (57-67 yr) had senescent ovaries with the unvarying high gonadotrophin and low oestrogen levels which are a consequence of ovarian failure.

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.

Melatonin: data consistent with a role in controlling ovarian function.

FSH and LH excretion were correlated with melatonin excretion in consecutive daily urines obtained from a normal adult female (27 days), a normal 11-year-old girl (28 days), and an 8-year-old girl with idiopathic sexual precocity (30 days). Additionally pregnanediol-3-glucuronide (PG) excretion was determined in the urines of the adult female. Gonadotropin and PG excretion patterns of the adult female were those associated with a normal menstrual cycle. Excretion of melatonin, mean +/- SD, (11.3 +/- 2.7 vs 4.7 +/- 1.4 ng/h, p less than 0.005) was greater and PG (38.3 +/- 81 vs 124.2 +/- 46.7 ug/h, p less than 0.005) was less during the first 13 days as compared to the subsequent 14 days. Gonadotropin and melatonin excretions correlated positively (first 13 days FSH, r = 0.828; rs = 0.815 and LH, r = 0.816; rs = 0.905, p less than 0.005 and subsequent 14 days FSH, r = 0.607; rs = 0.685, p less than 0.025 and LH, r = 0.490, p less than 0.05; rs = 0.638, p less than 0.025). Excretion of PG and melatonin did not correlate during the first 13 days. However, during the subsequent 14 days they correlated negatively (r = -0.679, p less than 0.005; rs = -0.620, p less than 0.025). During the 28-day period the gonadotropin and melatonin excretion patterns of the 11-year-old girl showed random fluctuations and correlated positively (FSH, r = 0.669; rs = 0.631 and LH, r = 0.690; rs = 0.695, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Relevance of urinary gonadotrophins.

The assay of urinary LH and FSH in first morning void urine can be used for the differential diagnosis between anorchism and bilateral cryptorchidism with impalpable testes. Furthermore, levels of urinary LH and FSH excretion and their response to intranasal stimulation with LH-RH prove helpful in the follow-up of patients under hormonal treatment, i.e. prolonged stimulation in hypogonadotrophic hypogonadism or suppression by an LH-RH analogue, for instance in precocious puberty. By increasing the sensitivity of the assay, the value of urinary gonadotrophins for the differential diagnosis and survey of hormonal treatment in very young children can be examined, and investigations of this kind are currently taking place. The method used obviously cannot assess the bioactivity of the excreted hormone, nor can it depict the pulsatility of gonadotrophin secretion.

Effects of severe dietary restriction on male reproductive hormones.

The reproductive hormone response to severe caloric restriction (600 Cal day-1) was studied in six men 33-67% over ideal body weight who completed a 32-day protocol consisting of three periods in the following order: control (4 days), maintenance protein and energy; diet A (14 days), 50 g lean beef protein plus 50 g casein; and diet B (14 days), 50 g lean beef protein plus 50 g carbohydrate. Weight loss (8.7-12.5 kg) was associated with a decrease in mean blood glucose [4.52 +/- 0.60 (+/- SEM), 3.49 +/- 0.29, and 3.80 +/- 0.30 mM] and an increase in beta-hydroxybutyrate (less than 0.10, 2.09 +/- 0.44, and 1.06 +/- 0.34 mM), as determined on the final morning of each period. On the same days, mean serum FSH and LH responses to LHRH infusion of 0.2 micrograms min-1 for 4 h (expressed as milliinternational units per ml area under the concentration-time curve) were: FSH, 1558 +/- 359, 1336 +/- 545, and 1337 +/- 321 (P = NS); and LH, 1730 +/- 545, 1612 +/- 481, and 1782 +/- 556 (P = NS), respectively. Basal serum FSH, LH, free testosterone (T), and total T changed, while 24-h urinary LH and FSH excretion increased on diet A only. Unlike 10 days of total fasting, during which the same amount of weight was lost, basal serum FSH and LHRH-stimulated serum FSH responses were both significantly diminished by 25%, and serum T was diminished by 19% (1), these same parameters were little changed by either low energy diet. The increased urinary excretion of FSH and LH during diet A suggests that greater ketosis increases renal gonadotropin clearance.

Return of Gonadal Function in Men With Prolactin-Secreting Pituitary Tumors

Gonadal function was evaluated in 10 men [33 +/- 17 (SD) yr] with pituitary tumors and hyperprolactinemia (47-2550 ng/ml) using nocturnal penile tumescence (NPT), semen analysis, urinary LH and FSH excretion, and diurnal variation of serum testosterone and PRL. Results were compared to 16 normal subjects (33 +/- 13 yr). NPT was decreased in tumor patients as demonstrated by reduced maximum circumference change (P less than 0.01) and total tumescence time (P less than 0.05). Semen analysis was examined in 5 patients able to produce specimens. All seminal parameters were significantly abnormal as demonstrated by oligospermia, asthenospermia, teratospermia , and elevated fructose. Urinary LH [570 +/- 72 (SE) vs. 838 +/- 22 mIU/h; P less than 0.01] and serum testosterone (235 +/- 60 vs. 625 +/- 63 ng/dl; P less than 0.01) were decreased in 9 tumor patients, all of whom had serum PRL levels above 50 ng/ml. Diurnal variation of serum PRL was absent in hyperprolactinemic patients whereas all had normal circadian changes in serum testosterone, although at a lower set point. Eight patients were followed for 6-13 months after reduction of serum PRL by surgery and/or drug therapy. Serum PRL reached normal levels in six men after 6 months of treatment. Selected individuals had an increase in serum LH after 2 months of treatment. Significant rises in serum testosterone occurred as early as 3 months and normal levels were found in six patients after 6-8 months of treatment. Only two subjects, however, demonstrated a normal semen analysis. These data suggest that men with serum PRL levels above 50 ng/ml maintain a normal diurnal pattern of serum testosterone at a lower set point, and demonstrate hypogonadism with reduced urinary LH excretion and NPT. In addition, routine seminal parameters are clearly abnormal and are both delayed and incomplete in their recovery.

Return of gonadal function in men with prolactin-secreting pituitary tumors.

Gonadal function was evaluated in 10 men [33 +/- 17 (SD) yr] with pituitary tumors and hyperprolactinemia (47-2550 ng/ml) using nocturnal penile tumescence (NPT), semen analysis, urinary LH and FSH excretion, and diurnal variation of serum testosterone and PRL. Results were compared to 16 normal subjects (33 +/- 13 yr). NPT was decreased in tumor patients as demonstrated by reduced maximum circumference change (P less than 0.01) and total tumescence time (P less than 0.05). Semen analysis was examined in 5 patients able to produce specimens. All seminal parameters were significantly abnormal as demonstrated by oligospermia, asthenospermia, teratospermia , and elevated fructose. Urinary LH [570 +/- 72 (SE) vs. 838 +/- 22 mIU/h; P less than 0.01] and serum testosterone (235 +/- 60 vs. 625 +/- 63 ng/dl; P less than 0.01) were decreased in 9 tumor patients, all of whom had serum PRL levels above 50 ng/ml. Diurnal variation of serum PRL was absent in hyperprolactinemic patients whereas all had normal circadian changes in serum testosterone, although at a lower set point. Eight patients were followed for 6-13 months after reduction of serum PRL by surgery and/or drug therapy. Serum PRL reached normal levels in six men after 6 months of treatment. Selected individuals had an increase in serum LH after 2 months of treatment. Significant rises in serum testosterone occurred as early as 3 months and normal levels were found in six patients after 6-8 months of treatment. Only two subjects, however, demonstrated a normal semen analysis. These data suggest that men with serum PRL levels above 50 ng/ml maintain a normal diurnal pattern of serum testosterone at a lower set point, and demonstrate hypogonadism with reduced urinary LH excretion and NPT. In addition, routine seminal parameters are clearly abnormal and are both delayed and incomplete in their recovery.