Biomedical subjects

W J Bremner

Publications and source records attributed to W J Bremner.

At least 91 records · Page 5Linked to original sources

PubMed1989

Luteal phase deficiency: characterization of reproductive hormones over the menstrual cycle.

The recurrent deficiency of progesterone (P) secretion by the corpus luteum has been associated with infertility and habitual abortion and given the clinical diagnosis of luteal phase deficiency (LPD). There is evidence that both follicular and luteal phase abnormalities can result in LPD cycles. In this study we have examined reproductive hormone levels and preovulatory follicular size in women with LPD (n = 10). For the purposes of this study, LPD was determined by an endometrial biopsy in the studied cycle that was more than 2 days out of phase. These biopsies were performed in women with infertility or habitual abortion who exhibited an out of phase biopsy in a prior cycle. The control group consisted of 28 normal women. Daily serum levels of the following hormones were determined in each subject: LH and FSH [immuno- and bioactive (LH-immuno and LH-bio)], P, estradiol (E2), and inhibin. The LPD women exhibited significant decreases in integrated luteal phase levels of inhibin [10,615 +/- 898 vs. 13,560 +/- 662 (U/L).days; P less than 0.02] and E2 [5,015 +/- 275 vs. 6,435 +/- 393 (pmol/L).days (1366 vs. 1753 (pg/mL).days); P less than 0.05] in addition to the expected decrease in P [280 +/- 23 vs. 420 +/- 23 (nmol/L).days (88 vs. 132 (ng/mL).days); P less than 0.01]. On days 6-11 after the LH surge (day 0), there was a significant (P less than 0.05) decrease in mean LH-bio levels in LPD compared with those in normal women (146 +/- 26 vs. 212 +/- 24 micrograms/L). The midcycle LH surge was deficient in LPD when both LH-immuno [482 +/- 30 vs. 672 +/- 43 (micrograms/L).days; P less than 0.01] and LH-bio [1711 +/- 179 vs. 2248 +/- 226 (micrograms/L).days; P less than 0.05] levels were compared with normal values. When comparing the follicular phase in LPD with that in normal women, similar follicle size, peak and integrated E2 levels, and mean LH and FSH (immuno and bio) levels were found. The only follicular phase abnormality noted in this study was decreased mean levels of serum inhibin in the early and midfollicular phases (221 +/- 19 vs. 308 +/- 25 U/L; P less than 0.01). In this group of women with LPD, low levels of inhibin in the follicular phase were consistent with the concept of a defect in function of the preovulatory follicle, possibly as a result of previously described defects in gonadotropin secretion in this condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Habitual↗

PubMed1989

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Abortion, Habitual↗

PubMed1988

Age-related alterations in the circadian rhythms of pulsatile luteinizing hormone and testosterone secretion in healthy men.

The effect of advancing age on the chronobiology of testosterone (T) and luteinizing hormone (LH) secretion in healthy men was investigated. Twenty young (average age 30.4 yrs) and 14 elderly (average age 70.4 yrs) men underwent 10 min blood sampling for 25 hrs to evaluate the circadian periodicity of LH, LH pulse frequency, and T. Using cosinor regression analysis, young men were found to have a significant (p less than .05) circadian variation in LH pulse frequency, with slowing of LH pulses during the night (maximum slowing at 2230 hr). There was also a tendency for LH pulse amplitude to increase at night (p = .06) in young men. However, no significant circadian pattern in LH pulse frequency or amplitude was detected in the elderly men. Mean LH by radioimmunoassay (RIA) and bioassay did not vary over the 24-hr period in either age group. Both young and elderly men had significant circadian rhythms in serum T, although the rhythm in elderly men was considerably blunted and was shifted in time compared to the young. These data provide evidence for age-related changes in the circadian rhythms of LH pulse frequency and T secretion and suggest that the LHRH pulse generator loses its circadian rhythmicity with normal aging in men.

Adult↗

PubMed1988

Modulation of luteinizing hormone pulse amplitude by the frequency of luteinizing hormone-releasing hormone stimulation and by testosterone in castrated, hypothalamic-lesioned male rats.

The frequency of spontaneous luteinizing hormone (LH) pulses is thought to be a direct result of the frequency of luteinizing hormone-releasing hormone (LHRH) pulses from the hypothalamus. By contrast, the amplitude of spontaneous LH pulses may be controlled by several factors other than the amplitude of LHRH pulses. We tested two hypotheses: 1) that LH pulse amplitude is determined in part by the frequency of LHRH pulses of constant magnitude, and 2) that testosterone (T) exerts a direct feedback effect on the pituitary gland to regulate LH pulse amplitude. Gonadal feedback was eliminated by castrating adult male rats (n = 20). Endogenous LHRH secretion was eliminated by lesioning the medial basal hypothalamus. Serum LH levels (0.19 +/- 0.04 ng/ml RP-2, mean +/- SEM) and T levels (0.15 +/- 0.02 ng/ml), measured several weeks after hypothalamic lesioning, confirmed the hypogonadotropic hypogonadal state of the animals. During a 8-h period, unanesthetized, unrestrained animals were injected with 40-ng pulses of LHRH via catheters into the jugular vein, and blood samples for LH measurement were drawn at 10-min intervals. The LHRH pulse interval was 20 min during the first 4 h in all animals. The pulse interval was doubled to 40 min in half of the animals (n = 10) during the next 4 hours; in the other 10 animals, the pulse interval was maintained constant at 20 min throughout the study. Within both of these groups, one-half of the animals (n = 5) were infused with T to achieve a physiological level of T in serum (2.46 +/- 0.36 ng/ml at 4 h), while the other half received vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Testosterone modulates the differential release of luteinizing hormone and follicle-stimulating hormone that occurs in response to changing gonadotropin-releasing hormone pulse frequency in the male monkey, Macaca fascicularis.

Selective elevations of plasma follicle-stimulating hormone (FSH) levels are characteristic of some physiological conditions, such as the early stages of human puberty, and in some disorders of testicular function, such as idiopathic oligospermia. We tested the hypotheses that a slow gonadotropin-releasing hormone (GnRH) pulse frequency favors a selective elevation of plasma FSH and that this is influenced by the circulating steroidal milieu. We administered exogenous GnRH at frequencies of once every 90 min (q 90 min) and once every 240 min (q 240 min) to castrated prepubertal male monkeys who had received either empty (sham) or testosterone (T)-filled Silastic capsules at the time of castration. At the end of each experimental frequency period, mean plasma levels of luteinizing hormone (LH) and FSH were measured. Plasma T levels were also measured. Animals with T implants had plasma levels of this hormone that were in the adult range (approximately equal to 8 ng/ml), whereas those with sham implants had plasma T levels in the prepubertal range (less than or equal to 4 ng/ml). In animals with sham implants, mean plasma FSH levels were markedly elevated at the slower GnRH pulse frequency (39.5 +/- 3.6 ng/ml following GnRH q 240 min compared with 23.7 +/- 2.8 ng/ml following GnRH q 90 min). This selective FSH elevation was not apparent in animals with T implants. Mean plasma LH levels were similar (approximately equal to 8 micrograms/ml) at the two GnRH pulse frequencies, in both T-treated and sham-implanted animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Relative roles of follicle-stimulating hormone and luteinizing hormone in the control of inhibin secretion in normal men.

The glycoprotein hormone inhibin is produced by the Sertoli cells of the testis under the influence of follicle-stimulating hormone (FSH) and is postulated in turn to inhibit FSH secretion. Luteinizing hormone (LH) is not recognized to have an important role in the control of inhibin secretion in any species. To determine the relative roles of FSH and LH in the control of inhibin secretion in man, we examined the effects of selective FSH and LH replacement on serum inhibin levels in normal men whose endogenous gonadotropins were suppressed by testosterone (T). After a 3-mo control period, nine men received 200 mg T enanthate i.m. weekly for 3-9 mo. During T treatment, serum LH and FSH levels were markedly suppressed and serum inhibin levels fell to 40% of control values. While continuing T, 3-5 mo of treatment with purified hFSH (n = 4) or hLH (n = 4) increased the respective serum gonadotropin level into the upper normal range and significantly increased inhibin levels back to 64 and 55% of control values, respectively. Supraphysiological LH replacement with high doses of human chorionic gonadotropin (n = 3) returned serum inhibin levels to 63% of control values. In no case did inhibin levels return fully to control levels. In conclusion, serum inhibin levels fell during gonadotropin suppression and were partially and approximately equally restored by either FSH or LH treatment. FSH presumably acts directly on the Sertoli cell to increase inhibin secretion whereas LH may act via increases in intratesticular T levels and/or other factor(s).

Adult↗

PubMed1988

Decreased serum inhibin levels in normal elderly men: evidence for a decline in Sertoli cell function with aging.

Compared to young men, normal elderly men have decreased sperm production despite elevated serum gonadotropin levels. To determine whether the seminiferous tubule defect in elderly men includes decreased Sertoli cell function, we measured serum immunoreactive inhibin concentrations in young and elderly men before and after clomiphene citrate (CC) administration. Thirty-eight healthy men, 19 young (aged 22-35 yr) and 19 elderly (aged 65-85 yr), were studied before CC administration. The mean baseline serum inhibin level was significantly lower (P less than 0.001) in the elderly men than in the young men [416 +/- 22 (+/- SE) vs. 588 +/- 30 U/L], while serum immunoreactive FSH and LH levels were higher in the older men, and bioactive FSH levels were similar in the two age groups. Eleven young men and 13 elderly men were studied after 1 week of CC administration. The mean serum inhibin level increased by 71%, from 566 +/- 36 to 970 +/- 82 U/L, in the young men, but it increased by only 24%, from 421 +/- 26 to 520 +/- 38 U/L, in the elderly men. Serum immunoreactive LH and bioactive and immunoreactive FSH concentrations increased to similar levels in both groups after CC administration. We conclude that the seminiferous tubule defect of elderly men includes decreased Sertoli cell function.

Adult↗

PubMed1988

Statistical evaluation of coincident prolactin and luteinizing hormone pulses during the normal menstrual cycle.

The purpose of this work was 2-fold. First, we sought to develop statistical criteria by which it could be established that the coincident occurrence of pulses of two different hormones exceeds that which would occur by chance alone, thereby suggesting that secretion of the two hormones is either coupled or controlled from a single source generator. Using computer simulations of uncoupled pulse generators operating at different frequencies, we were able to derive the appropriate statistical criteria and to apply them to achieve our second objective, to determine whether the occasional coincidence of plasma LH and serum PRL pulses that occurs throughout the menstrual cycle in normal women exceeds that which would happen by chance. The results of the computer simulations indicated that pulses emanating from two completely independent oscillators will occur coincidently at a predictable rate, despite the fact that the generator sources are not coupled; moreover, the rate of coincidence is increased when the pulse frequency of one of the source generators is increased. Using this knowledge and the statistical criteria we derived, we analyzed the coincidence of LH and PRL pulses in five normal women during their early follicular, late follicular, and midluteal phases and in another five women during their late luteal phase. We found that the number of PRL pulses that occurred coincidently with LH pulses consistently exceeded that which would be predicted if the two pulse generators were operating completely independently of one another; however, only during the late follicular and late luteal phases was the coincidence level between LH and PRL pulses sufficiently high in a sufficient number of women to conclude that there was coupling between the pulse sources. These studies suggest, first, that stringent and rigorous statistical criteria must be applied to the analysis of spontaneously coincident secretory phenomena before it can be deduced that two pulse generators are indeed coupled, and second, that the pulse generators governing the secretion of PRL and LH are probably coupled, at least during certain phases of the menstrual cycle.

Adult↗

PubMed1988

Stimulation of serum inhibin concentrations by gonadotropin-releasing hormone in men with idiopathic hypogonadotropic hypogonadism.

Inhibin is a gonadal hormone thought to be important in FSH regulation. We investigated the effects of the hypogonadotropic state and subsequent GnRH-induced increases in gonadotropin levels on inhibin secretion. Serum levels of inhibin, LH, FSH, and testosterone (T) as well as sperm concentrations were measured in 5 men with idiopathic hypogonadotropic hypogonadism (IHH) before (baseline) and during 8 weeks of GnRH therapy (5 micrograms, sc, every 2 h). Baseline and peak inhibin levels were compared to those in a group of 19 normal men. Before GnRH administration, the mean serum inhibin level was significantly lower in the IHH men than in the normal men [166 +/- 56 (+/- SE) vs. 588 +/- 30 U/L; P less than 0.001]. Serum inhibin levels rose after 1 week of GnRH therapy (P less than 0.05) and remained higher than the baseline level thereafter. The mean peak inhibin level during GnRH administration was lower than the mean value in normal men (485 +/- 166 vs. 588 +/- 30 U/L; P less than 0.05). Serum LH and FSH levels rose promptly to the midnormal range or slightly above it. Serum T levels did not significantly increase until 4-5 weeks of GnRH administration and remained in the low normal range. All IHH men were azoospermic throughout the study. These data are consistent with the hypothesis that inhibin is produced by the testis under gonadotropin control. They also suggest the possibility of defective Sertoli and Leydig cell function in men with IHH, since the men's serum inhibin and T levels did not rise to the same extent as did their normalized serum gonadotropin levels during GnRH administration.

Adult↗

PubMed1988

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.

Adult↗

PubMed1988

High serum cortisol levels in exercise-associated amenorrhea.

OBJECTIVE: To determine whether basal cortisol levels are elevated in exercise-associated amenorrhea. DESIGN: Survey, with hormone levels measured weekly for 1 month and patients followed clinically for 6 months. SETTING: Volunteers were recruited through media advertisements and fliers. PARTICIPANTS: Ninety-two women were enrolled; 71 (77%) completed the study. Subjects were grouped by menstrual and activity histories reported by a self-administered questionnaire. After 6 months, final groups were assigned: amenorrheic athletes, 19; eumenorrheic athletes, 35; a transition group of amenorrheic athletes who had resumed menses after entering the study, 7; and normal cyclic nonathletes, 10. INTERVENTIONS: Four weekly resting blood samples (0800 to 1000 hours) were obtained and measured for cortisol, estradiol, progesterone, and prolactin levels. Lumbar bone mineral density was measured by dual-photon densitometry. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SE) cortisol levels were higher in amenorrheic athletes (585 +/- 33 nmol/L) than in eumenorrheic athletes (411 +/- 14 nmol/L), transition athletes (378 +/- 33 nmol/L), or nonathletic women (397 +/- 30 nmol/L) (P less than 0.01). Of nine women with abnormally high cortisol levels (greater than 579 nmol/L), eight were amenorrheic athletes, and one was a eumenorrheic athlete. Bone mineral density was lower in amenorrheic athletes than in the other three groups (P less than 0.01). CONCLUSIONS: Increased glucocorticoid levels may be an etiologic factor in exercise-associated amenorrhea. High cortisol levels could also contribute to decreased bone density. The failure of amenorrheic athletes with hypercortisolemia to regain menses within 6 months suggests that they are at risk for a prolonged acyclic state.

Adult↗

PubMed1988

The corpus luteum: determinants of progesterone secretion in the normal menstrual cycle.

Fourteen normal volunteers were studied during one menstrual cycle. Follicular development, the luteinizing hormone (LH) surge, and the relationship between LH and progesterone secretion in the luteal phase were studied to determine the factors that control corpus luteum function. Follicular development was assessed by measuring follicle size and daily estradiol (E2) levels; the LH surge was quantified by determining the area under the curve. Although there was a significant positive correlation between mean follicle diameter and E2, these same parameters did not correlate with postovulatory progesterone secretion; nor did the LH surge correlate with progesterone secretion. A decrease in LH pulse frequency occurred in moving from the follicular to the luteal phase. There was a trend toward an increase in the late luteal LH pulse frequency compared with the midluteal phase, but this was not significant. Progesterone was secreted in an intermittent (pulsatile) fashion in the midluteal and late luteal phases. The general decrease in progesterone in the latter days of the menstrual cycle appears to be due to a decrease in the progesterone pulse amplitude. A significant correlation between LH and progesterone was present when the data were "smoothed"; however, there was not a significant synchrony for LH and progesterone pulses for most of the subjects when the initial data were analyzed by objective criteria. Progesterone secretion in the luteal phase is quite complex and leads to highly variable serum levels of progesterone when samples are obtained at random from normal women.

Adult↗

PubMed1987

Treatment of stage D2 prostatic carcinoma with combined gonadal and adrenal suppression in a 60-year-old man.

A 60-year-old man with stage D2 prostatic carcinoma received treatment with a new luteinizing hormone-releasing hormone superagonist. After a seven-month remission; relapse of the disease occurred and an adrenal-suppressing dose of dexamethasone was added. The resulting combined gonadal and adrenal suppression led to another remission that lasted five months. This case supports other observations of the importance of adrenal androgen production in the pathobiology of prostatic carcinoma.

Adenocarcinoma↗

PubMed1987

Endocrinology of the hypothalamic-pituitary-testicular axis with particular reference to the hormonal control of spermatogenesis.

The normal physiology of the hypothalamic-pituitary-testicular axis in man is reviewed. According to current concepts, LH plays an important role in the initiation and maintenance of spermatogenesis by stimulating Leydig cell production of high concentrations of T within the testes. FSH is thought to be important in spermatid maturation (spermiogenesis) during the initiation of spermatogenesis by stimulation of Sertoli cells. Studies of selective gonadotrophin replacement in experimentally-induced hypogonadotrophic hypogonadal men demonstrate that qualitatively normal sperm production can be achieved by replacement of either LH or FSH alone, but both LH and FSH are necessary to maintain quantitatively normal spermatogenesis. Studies of gonadotrophin replacement in spontaneously-occurring hypogonadotrophic men suggest that the requirement for FSH activity to stimulate sperm production is greatest during the initiation of sperm production at the time of puberty. The initiation of spermatogenesis in postpubertal men with acquired hypogonadotrophic hypogonadism and the maintenance of spermatogenesis after its initiation can often be achieved with LH activity alone.

Chorionic Gonadotropin↗

PubMed1987

Differential control of luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone pulse frequency in man.

To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low [28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively], and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response.

Adult↗

PubMed1987

Serum bioactive and immunoreactive follicle-stimulating hormone levels and the response to clomiphene in healthy young and elderly men.

Testicular function declines with normal aging, while serum immunoreactive LH and FSH levels increase. Since there are reports of an age-related decrease in the ratio of bioactivity to immunoreactivity (B/I ratio) for LH, we used a newly available bioassay for FSH to assess age-associated changes in the bioactivity and B/I ratio of FSH in man. Thirty-nine healthy men (23 young and 16 elderly) had single blood samples drawn. In addition, a subset of these men (12 young and 13 elderly) underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Hourly blood samples from the 24-h sampling were pooled, and these, along with the single samples, were assayed for FSH by an in vitro bioassay system, using estrogen production by immature rat granulosa cells as the end point, and by RIA. Baseline single sample mean FSH, as measured by bioassay, was similar in young and elderly men [386 +/- 98 (+/- SEM) and 342 +/- 77 ng/mL, respectively]. Baseline mean FSH, measured by RIA, was significantly higher (P less than 0.001) in elderly men (234 +/- 31 ng/mL) than in young men (122 +/- 12 ng/mL). The baseline FSH B/I ratio based on single sampling was significantly lower (P less than 0.01) in elderly men (1.4 +/- 0.2) than in young men (2.7 +/- 0.3). In the men given CC and sampled for 24 h, mean bioactive FSH levels increased significantly in both the young (1180 +/- 282 ng/mL) and the elderly (992 +/- 227 ng/mL; P less than 0.01 for both values compared to baseline). Mean FSH by RIA also increased to similar levels in these young (217 +/- 34 ng/mL) and elderly (258 +/- 45 ng/mL) men. The FSH B/I ratio was 4.8 +/- 0.8 in young and 4.7 +/- 1.1 in elderly men after CC administration. We conclude that serum bioactive FSH levels are similar in elderly and young men, suggesting that the age-related decline in testicular function in man cannot be explained by a chronic deficiency in FSH stimulation; elderly men have a lower serum FSH B/I ratio than young men, which may reflect changes in the circulating form of FSH with aging; and administration of CC to young and elderly men increases both bioactive and immunoreactive serum FSH, implying preserved hypothalamic-pituitary responsiveness in the elderly.

Adult↗

PubMed1987

Corpus luteum insufficiency induced by a rapid gonadotropin-releasing hormone-induced gonadotropin secretion pattern in the follicular phase.

The pulse frequency of LH and FSH (and by inference, GnRH) is a major determinant of the relative baseline plasma levels of LH and FSH. Luteal phase deficiency has been reported to be associated with increased gonadotropin pulse frequency and inadequate preovulatory follicular development. In this study we induced in normal women a supraphysiological gonadotropin pulse frequency in the follicular phase to determine its effect on follicular development and corpus luteum function. Specifically, we tested the hypothesis that a supraphysiological GnRH pulse frequency would result in deficient luteal phase production of progesterone. The subjects were six normal ovulatory women (age range, 23-35 yr). They were initially studied during a control cycle (cycle 1). Then, 25 ng/kg GnRH was administered iv every 30 min from the early follicular phase of the next cycle (cycle 2) until ovulation occurred. GnRH administration resulted in increased follicular phase plasma LH and FSH levels and LH to FSH ratios, multiple preovulatory follicles (mean, 2.8) with increased mean integrated estradiol [1302 (pg/mL)day (cycle 1) vs. 2550 (pg/mL)day (cycle 2); P less than 0.05; 4780 vs. 9360 (pmol/L)day, Systeme International units], spontaneous ovulation, decreased luteal phase plasma immunoreactive and bioactive LH levels, decreased luteal phase length [13.5 days (cycle 1) vs. 8.8 days (cycle 2); P less than 0.05], and decreased mean integrated progesterone secretion [152 (ng/mL)day (cycle 1) vs. 66 (ng/mL)day (cycle 2); P less than 0.01; 482 vs. 209 (nmol/L)day, Systeme International units]. We conclude that high frequency LH and FSH secretion during the follicular phase can induce inadequate progesterone secretion during the subsequent luteal phase, and we infer that the pathophysiological basis for this induced luteal phase deficiency is decreased LH support of corpus luteum function.

Adult↗

PubMed1987

The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate.

Serum testosterone (T) levels in men decline with age while serum LH levels, as measured by RIA, increase. To assess if the decline in serum T levels in healthy aging men is paralleled by an age-related decline in the bioavailable non-sex hormone-binding globulin (SHBG)-bound fraction of T and to determine whether there are age-related changes in LH secretion or LH control of T production, we studied 29 young (aged 22-35 yr) and 26 elderly (aged 65-84 yr) healthy men. All men had single random blood samples drawn, and 14 men in each age group underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Both mean 24-h serum total T levels and non-SHBG-bound T were reduced in elderly men compared to those in young men (P less than 0.05), while estradiol and SHBG levels were similar in the 2 age groups. Serum FSH determined by RIA and LH by RIA and bioassay were higher in the elderly men compared to those in young men (P less than 0.05), but the ratios of LH bioactivity to immunoreactivity and the LH pulse frequency and amplitude were similar. After CC administration, mean serum total T and non-SHBG-bound levels in young men increased by 100% and 304%, respectively, while in older men these values increased by only 32% and 8%, respectively. However, CC-stimulated LH pulse characteristics and serum levels of estradiol, SHBG, FSH, and bioactive and immunoreactive LH were similar in the 2 groups. Thus, both at baseline and after CC stimulation, elderly men had significantly lower serum total T and non-SHBG-bound (bioavailable) T levels than did young men, despite similar or increased levels of bioactive LH and similar bioactive to immunoreactive LH ratios and LH pulse characteristics. These results suggest that major age-related changes in the hypothalamic-pituitary-testicular axis occur at the level of the testes and are manifested by decreased responsiveness to bioactive LH. Administration of CC to young and elderly men resulted in similar changes in LH pulse characteristics and LH bioactivity and immunoreactivity, suggesting preserved hypothalamic-pituitary responsiveness in the elderly.

Adult↗