Biomedical subjects

W J Bremner

Publications and source records attributed to W J Bremner.

At least 55 records · Page 3Linked to original sources

PubMed1995

Dose effects of the gonadotropin-releasing hormone antagonist, Nal-Glu, combined with testosterone enanthate on gonadotropin levels in normal men.

OBJECTIVE: To test the hypothesis that over a 4-week treatment period, Nal-Glu GnRH antagonist ([AcD2Nal1, D4ClPhe2, D3Pal3, Arg5, DGlu6 [AA], DAla10] GnRH) at a dose of 200 micrograms/kg per day SC would suppress levels of immunologically active and biologically active LH and FSH more completely than a dose of 100 micrograms/kg per day. DESIGN: Placebo controlled clinical study. SETTING: A university community. SUBJECTS: Thirty normal male volunteers. INTERVENTIONS: We administered Nal-Glu at doses of 0, 100, and 200 micrograms/kg body weight per day in combination with T enanthate, 50 mg IM weekly, to separate groups of men (9 or 10 men per group) for 4 weeks. RESULTS: Serum levels of immunologically active and biologically active gonadotropins were suppressed similarly in both groups of men who received Nal-Glu; this suppression was significantly greater than in the men who received placebo + T. Local side effects were more severe in the Nal-Glu 200 micrograms/kg per day group. CONCLUSIONS: Administration of Nal-Glu in combination with T suppresses gonadotropins more completely than does T alone, but at doses > 100 micrograms/kg, gonadotropins are not suppressed additionally with larger doses of Nal-Glu. Subjects experienced greater local discomfort and side effects with the higher dosage. These findings suggest that dosages of Nal-Glu of > 100 micrograms/kg per day may have no advantage over the 100-micrograms/kg dose in a male contraceptive regimen.

Adult↗

PubMed1995

Testosterone enanthate at a dose of 200 mg/week decreases HDL-cholesterol levels in healthy men.

The concept that androgen alone can provide an effective male contraceptive has been tested in a multicentre, multiphase trial by the World Health Organization. Results from this trial showed that an ester of testosterone, testosterone enanthate (TE), administered at a dose of 200 mg/week, has a very high contraceptive efficacy, and suggested that, at least in some populations, androgen alone might provide a viable option for the control of male fertility. It has been claimed that testosterone represents one of the gender-related risk factors for coronary artery disease (CAD) in men. Epidemiological and interventional studies have failed to establish a convincing relationship between testosterone and high density lipoprotein cholesterol (HDL-C). Therefore, there is concern about possible negative effects on lipoprotein asset of an androgen-alone male contraceptive. In this study we analysed the effects of long-term (12 months) administration of TE (200 mg/week) in normal healthy men. Blood samples (six men > 10 h fast = Group 1; 30 men > 4 h fast = Group 2) were drawn from 36 men, monthly before the beginning of the injections (control), every 3 months throughout the study period (treatment), and 1 month after stopping TE injections (recovery). Total cholesterol (chol), triglycerides, HDL-C and LDL-C levels were measured in these samples. Biochemical parameters were also monitored. TE administration induced a significant decrease (15-20%) in HDL-C levels that was of comparable magnitude in men from both groups (fasting and non-fasting) and occurred regardless of basal HDL-C levels. No statistically significant effect on other lipoproteins was detected. Considering all men together, HDL-C levels were decreased in 78% of the men by month 3, 83% by month 6, 94% by month 9 and 97% by month 12 of treatment. In all men the HDL-C decrease was reversible within 1 month of stopping TE administration. It is concluded that: (1) injection of 200 mg TE/week causes a 15-20% decrease in HDL-C in normal men with no effect on other lipoproteins, (2) the suppressive effect of TE is maintained throughout the 1-year-injection period, and a direct relationship between the duration of TE administration and the proportion of men showing decreased HDL-C levels, was observed. (3) The HDL-C decrease was reversible within 1 month of stopping TE administration. These data will be important in designing further studies on male contraception, and in interpreting the relationship between testosterone levels, HDL-C levels and potential cardiovascular risk.

Adult↗

PubMed1994

Short-term fasting in normal women: absence of effects on gonadotrophin secretion and the menstrual cycle.

OBJECTIVE: In men and male monkeys, a short-term fast has been reported to have a major effect on the reproductive axis. In this study we investigated the effects of a short-term fast (72 hours) on female reproductive hormone secretion and menstrual function. DESIGN: The study consisted of an admission day (control), three successive fasting days (fast 1, 2 and 3) and a refeeding day (post fast). PATIENTS: Eight normal cycling women, ages 21-35, within 10% of ideal body weight, were fasted for 72 hours during the follicular phase of their menstrual cycle. MEASUREMENTS: On the admission day, the last day of the fast and the day of refeeding, blood samples were collected at 10-minute intervals from 0800 to 2000 h for determination of the LH pulse pattern. Daily determinations of immuno LH, FSH, oestradiol (E) and progesterone (P) were performed throughout the menstrual cycle in which the fast occurred. RESULTS: Throughout the fasting days, the consistently low serum levels of glucose and insulin confirmed that all the subjects were fasting. However, in spite of profound metabolic changes and a significant loss of weight, the short-term fast did not have discernible effects upon the reproductive hormones studied. Basal mean LH concentrations did not show any significant variation throughout the study period. The mean +/- SEM number of LH pulses was 13.4 +/- 1.5/12 h on the control day, 12.4 +/- 1.2/12 h (NS) on the third day of fasting and 11.0 +/- 1.5/12 h (NS) the day of refeeding. Each woman maintained a physiological pattern of LH, FSH, E and P throughout the menstrual cycle including the LH surge; ultrasound evidence of normal growth of a dominant follicle; and cycle length consistent with previous cycles. CONCLUSIONS: Our results indicate that in spite of profound metabolic changes, a 72-hour fast during the follicular phase does not affect the menstrual cycle of normal cycling women. It appears that the female reproductive axis during this phase of the cycle is more resistant to an acute caloric deprivation than that of men or male monkeys.

Adult↗

PubMed1994

Follistatin decreases activin-stimulated FSH secretion with no effect on GnRH-stimulated FSH secretion in prepubertal male monkeys.

Follistatin is an activin-binding glycoprotein that decreases FSH secretion in vitro and in vivo in rats. The mechanism by which follistatin acts is unclear, but it has been suggested that it may bind endogenous activin and neutralize its effects. In this study, we wished to test the ability of follistatin to suppress FSH secretion in vivo in primates whose FSH secretion has been stimulated by activin or by GnRH. Six prepubertal male monkeys were injected intravenously with human recombinant follistatin at the dose of 90 micrograms/kg or 180 micrograms/kg plus activin (90 micrograms/kg) or GnRH (10 micrograms/kg). Frequent blood samples were drawn for 12 hours following each injection. Bio FSH and LH levels were measured in those samples. GnRH and activin each stimulated FSH bioactivity. Both doses of follistatin significantly inhibited the activin-induced increase in FSH (p < 0.05). The GnRH-induced increase in FSH was not affected by follistatin. LH levels were not affected by follistatin in any of the studies. These data suggest that follistatin can suppress the activin-induced increase in FSH in primates and is consistent with the hypothesis that follistatin can block the physiological effects of endogenous activin in primates. This effect is likely to be due to the binding of follistatin to activin either in the peripheral circulation or at the pituitary level.

Activins↗

PubMed1994

Immunohistochemical localization of androgen receptors in the rat testis: evidence for stage-dependent expression and regulation by androgens.

Androgens are essential for the maintenance of normal spermatogenesis in the rat. We assessed the sites, developmental pattern, and hormonal control of androgen receptors (AR) in the rat testis. Adult male rats were studied after 1) no treatment; 2) ethane dimethane sulfonate (EDS), which eradicates Leydig cells and endogenous testosterone (T); 3) EDS plus T replacement beginning at the time of EDS administration; or 4) methoxyacetic acid, which leads to the loss of specific germ cell types. Testes were also obtained from normal immature rats (aged 5, 14, 16, 21, 28, 31, 35, 38, and 45 days). After microwave antigen retrieval, immunohistochemistry was performed using a rabbit polyclonal antibody (Novocastra) raised against a peptide unique to the N-terminal region of the AR and detection with biotinylated swine antirabbit immunoglobulin G, avidin-biotin complex/alkaline phosphatase, and nitroblue tetrazolium salt (NBT)/5 bromo-4-chloro-3-indolylphosphate (BCIP) substrate. In adults, nuclear immunostaining of Sertoli cells (SC) increased progressively in intensity from stages II through VII of the spermatogenic cycle, and then declined precipitously during stage VIII to become barely detectable in stages IX-XIII. Prominent AR immunostaining was also evident in peritubular myoid cells, arterioles, and interstitial cells; staining in these cells did not vary with the stage of the cycle of the adjacent tubules. EDS caused a severe loss of AR immunostaining in all cell types. Replacement of T in EDS-treated animals resulted in a pattern of AR immunostaining comparable to that in controls, although staining intensity was reduced. Methoxyacetic acid administration did not affect the pattern of AR staining. In immature rats, peritubular myoid cell immunostaining was prominent from day 5; SC staining was detectable on day 5, increased in intensity with age, and became stage dependent between days 21-35. The following conclusions were reached. 1) Immunohistochemically detectable AR expression in SC occurs predominantly in stages II-VII of the spermatogenic cycle, with highest levels at stage VII. 2) AR immunostaining is also prominent in peritubular myoid cells, arterioles, and Leydig cells (but not in germ cells), but is unrelated to the stage of adjacent tubules. 3) Endogenous T and/or its metabolites control the expression of AR in the testis. 4) AR immunostaining is detectable by day 5 of age and becomes stage specific in SC between days 21-35.

Acetates↗

PubMed1994

Effects of endogenous testosterone and estradiol on sexual behavior in normal young men.

The importance of androgens in establishing and maintaining sexual function in males of most species is well recognized. Estrogens also stimulate male sexual function in some species. In men, most studies of androgen effects on behavior have used hypogonadal men as an experimental model; much less is known about the role of endogenous testosterone (T) or estradiol (E2) in the regulation of behavior in healthy, eugonadal men. In a randomized, double-blind study, we used a GnRH antagonist, Nal-Glu, without T replacement, to induce acute, profound, reversible gonadal steroid deficiency in 9 normal men for 6 weeks (Nal-Glu alone). We also studied the effects of partial androgen replacement by administering Nal-Glu together with T enanthate, 50 mg im weekly, to 10 other men. A third group of 10 men received Nal-Glu plus T, 100 mg im weekly. We studied the role of endogenous E2 by administering Nal-Glu plus T, 100 mg im weekly, plus an aromatase inhibitor, testolactone (Teslac), 250 mg po qid, to 10 additional men (Nal - Glu + T + Teslac). Nine men received placebo injections and tablets. All subjects completed a behavioral questionnaire during the pretreatment period, at weeks 2, 4, and 6 of treatment, and at 3 weeks posttreatment. Men who received Nal-Glu alone became profoundly hypogonadal within 1 week after treatment began. Serum T levels did not change significantly in the controls and in the men who received full T replacement but decreased to approximately half the baseline level in men who received partial T replacement. E2 levels decreased profoundly in men who received Nal-Glu alone or Nal - Glu + T + Teslac and to a lesser degree in men who received partial T replacement. In men who received Nal-Glu alone, there were clinically and statistically significant decreases in the frequency of sexual desire, sexual fantasies, and intercourse at 4-6 weeks. These men also showed a strong trend (P = 0.55) towards decreased spontaneous erections after 4 and 6 weeks of treatment. A significant decrease in the frequency of masturbation was evident after 6 weeks. All measures returned to normal by posttreatment week 3. There was a trend toward increased aggression in the hypogonadal men, but this did not reach statistical significance. No changes in satisfaction or happiness with their partners were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1994

Physiological levels of estradiol stimulate plasma high density lipoprotein2 cholesterol levels in normal men.

Premenopausal women have a lower risk of coronary artery disease than men or postmenopausal women; estrogens are thought to contribute to this lower risk. Administration of exogenous estrogen to post-menopausal women increases plasma high density lipoprotein (HDL) cholesterol and may reduce mortality from coronary disease in users. Although many investigations have examined the roles of estrogen in the regulation of lipoproteins in women, little attention has been directed to estrogen regulation of lipids in men. We designed a paradigm to study the role of physiological levels of estradiol (E2) on plasma lipoproteins in healthy men. We used a GnRH antagonist, Nal-Glu, to suppress endogenous steroid hormones in healthy men. We then administered testosterone (T) enanthate (100 mg, im, weekly) to restore T levels to the baseline range, and we administered an aromatase inhibitor, testolactone (Teslac), to prevent the normal conversion of T to E2, thereby producing a selective estrogen deficiency state in normal young men. As controls, we administered Nal-Glu and T along with placebo Teslac to a separate group of men; a third group of men received all placebo medications. We found that in men who received Nal-Glu plus T plus Teslac, E2 levels were profoundly suppressed during treatment, whereas T levels remained in the baseline range. Plasma HDL cholesterol, particularly, the HDL2 fraction, decreased significantly in response to the low serum E2 level. Plasma apoprotein-AI levels also decreased significantly. Plasma LDL and triglyceride levels did not change. All hormone and lipoprotein parameters returned to baseline within 4 weeks after treatment ended. In men who received Nal-Glu plus T, plasma HDL and apoprotein-AI decreased, but these decreases did not achieve statistical significance. Only a small decrease in HDL2 cholesterol was seen in these men. There were no hormonal or lipid changes in the placebo group. We conclude that in men, physiological levels of E2 are important in maintaining plasma levels of HDL cholesterol, especially the HDL2 fraction. These observations suggest that estrogen, in the amount normally produced in men, may offer some degree of protection against cardiovascular disease in males, as they do in women.

Adult↗

PubMed1994

Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men.

In addition to their use as replacement therapy for hypogonadal males, androgens, particularly testosterone (T), are being explored as potential hormonal male contraceptive agents, alone or in combination with other compounds. Androgens have regulatory effects on a variety of physiological systems in addition to gonadotropin secretion and spermatogenesis. Therefore, as hormonal contraceptive regiments that alter serum T levels are explored, it is important to evaluate their effects on these aspects of normal male physiology. The effects of exogenous T on suppression of spermatogenesis in 19 healthy men were recently compared, using a T dosage of 200 mg im/week for 20 weeks. Before treatment, the men were evaluated during a 3-month pretreatment period, and after treatment, they were followed for 4-6 months or until their sperm counts normalized. Because of the lack of information regarding the effects of exogenous T on nonreproductive physiology, we examined the effects of high-dose T on plasma lipids, calcium metabolism, and sexual behavior in our subjects. Mean serum T and estradiol levels increased significantly during the treatment period. Plasma high-density lipoprotein (HDL) cholesterol levels decreased significantly within the first month and remained suppressed during the duration of T administration. At the end of the treatment period, mean plasma HDL cholesterol had decreased by 13 +/- 2% (P < 0.05); plasma levels of HDL2, HDL3, and apoprotein AI also decreased significantly; mean levels of low density lipoprotein cholesterol and triglycerides were unchanged. After 1 month of the recovery period, plasma HDL levels had returned to the baseline range. Serum calcium levels decreased slightly during treatment; this decrease was statistically significant. Urinary calcium excretion did not change. Mean levels of serum intact PTH increased by 84 +/- 17% (P < 0.05) during T administration; in contrast, 25-hydroxyvitamin D levels decreased by 16 +/- 4% (P < 0.05), and 1,25-dihydroxyvitamin D levels did not change significantly. All markers of calcium metabolism returned to baseline during the posttreatment period. Little change was found in self-reported sexual and aggressive behaviors during the study. There was a trend toward increased arousal and spontaneous erections during T administration, but this did not reach statistical significance. Frequency of sexual intercourse, masturbation, and kissing and fondling did not change, nor was the subjects' satisfaction in their relationships affected by T administration. Mean body weight increased by 4.0 +/- 0.5 kg. Approximately half the men noted mild acne. Body weight and acne symptoms returned to baseline during the recovery period.(ABSTRACT TRUNCATED AT 400 WORDS)

Acne Vulgaris↗

PubMed1994

Prospects for new hormonal male contraceptives.

Overpopulation is a paramount global crisis, as it underlies virtually all major worldwide problems, including poverty, malnutrition, and warfare. It is imperative that proliferation be curbed by expediting reductions in fertility. This article discusses the demand for and acceptability of male contraceptives and the process of spermatogenesis. Endocrine control of spermatogenesis, and potential sites for disruption of male fertility, including steroid combinations and GnRH agonists and antagonists are reviewed also. Risks and benefits of these approaches are considered.

Androgen Antagonists↗

PubMed1994

Decreased testosterone levels in men with rheumatoid arthritis: effect of low dose prednisone therapy.

OBJECTIVE: To determine whether men with rheumatoid arthritis (RA) have abnormal hypothalamic-pituitary-gonadal axis function and to measure the effects of low dose prednisone therapy in these patients. METHODS: We measured testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) in 36 men aged 38-75 (mean age +/- 1 sd = 62 +/- 10 years) who had longstanding active RA (mean disease duration = 17 +/- 12 years) and in 70 healthy elderly male controls, aged 53-83 (mean age 68 = +/- 6 years). We divided the group with RA into those taking no prednisone (n = 12) and those taking 5 to 10 mg/day of prednisone (n = 24) and analyzed these groups separately to determine whether low doses of prednisone affected testosterone levels. RESULTS: Compared to the healthy controls, patients with RA not taking prednisone had normal testosterone levels but significantly elevated levels of FSH and LH (p < 0.01 for both comparisons). In contrast, patients with RA taking prednisone had significantly lower testosterone levels (p < 0.05), but levels of FSH and LH were only slightly elevated compared to controls. Compared to patients not taking prednisone, patients taking prednisone had lower levels of testosterone, FSH, and LH. CONCLUSION: Male patients with RA who are not taking prednisone have significantly elevated levels of FSH and LH with normal testosterone levels, suggesting a state of compensated partial gonadal failure. Male patients with RA taking low doses of prednisone have lower testosterone and gonadotropin levels, suggesting that prednisone may suppress the hypothalmic-pituitary-testicular axis. Since testosterone affects immune function as well as bone and muscle metabolism, androgen deficiency in some men with RA may predispose these patients to more severe disease and to increased complications of steroid therapy such as myopathy and osteoporosis.

Adult↗

PubMed1994

Preservation of fertility despite subnormal gonadotropin and testosterone levels after cessation of pulsatile gonadotropin-releasing hormone therapy in a man with Kallmann's syndrome.

A man with IHH and anosmia presented in 1980. He was successfully treated with various hormonal regimens; four children were conceived with hCG or pulsatile GnRH therapy. The patient discontinued GnRH after the fourth child was conceived, and testosterone enanthate injections were prescribed. However, he took the injections only briefly and 15 months later he demonstrated continuing spermatogenesis despite low serum FSH and LH levels. His wife successfully became pregnant. This case adds to the recognized range of recovery in IHH, with fertility despite stopping hormonal therapy and despite low serum gonadotropin and T levels.

Adult↗

PubMed1993

Single-dose administration of the gonadotropin-releasing hormone antagonist, Nal-Lys (antide) to healthy men.

OBJECTIVE: To evaluate the ability the Nal-Lys GnRH antagonist ([N-Ac-Nal (2)1, 4ClDPhe2, D3Pal3, Lys (Nic)5, D-Lys(Nic)6, Lys (iPr)8, D-Ala10] to suppress gonadotropins and T in humans and to assess its duration of action and its local effects. DESIGN: Placebo-controlled clinical study. SETTING: A university community. SUBJECTS: Seven normal male volunteers. INTERVENTIONS: We administered single injections of Nal-Lys (0, 10, 25, and 50 micrograms/kg body weight). Blood samples were collected before and at frequent time intervals after injection. RESULTS: Nal-Lys caused only minor local effects. At the higher doses (25 and 50 micrograms/kg), serum LH and T levels were suppressed to 50% to 70% of baseline; serum FSH levels were suppressed to 70% to 80% of baseline, and levels of all three hormones returned to basal values within 24 hours after injection. CONCLUSIONS: In humans, Nal-Lys has similar potency and duration of action to other antagonists and produces fewer local side effects. However, the utility of Nal-Lys is limited by formulation difficulties; current efforts are directed at improving the formulation in order to explore the potential clinical uses of this peptide.

Adult↗

PubMed1993

Reduced inhibin and elevated gonadotropin levels in early pubertal boys with testicular defects.

In the prepubertal quiescent period, the control of gonadotropin secretion is assumed to be mediated by neuroendocrine inhibitory mechanisms, whereas little or no effect is thought to be mediated by the gonad. However, in pubertal-aged children with primary gonadal failure, gonadotropins increase to supranormal levels, suggesting that gonadal factors become more important in the control of gonadotropin secretion at that age. These gonadal factors have been poorly characterized so far. To clarify the relationship of inhibin and testosterone to the control of gonadotropin secretion during sexual maturation, we examined serum inhibin, testosterone, LH, and FSH concentrations in 10 boys with testicular defects and in nine healthy boys, in prepuberty and in early puberty. Serum was obtained at 15-min intervals for at least 6 h during the night. Prepubertal-aged boys with testicular defects had only slightly higher FSH levels than healthy boys, and their LH and inhibin levels were no different. In contrast, pubertal-aged boys with testicular defects had higher LH and FSH levels and lower inhibin levels than healthy boys. In prepubertal-aged boys, no correlation was found between individual mean inhibin level and mean FSH or LH level. In contrast, in pubertal-aged boys, an inverse nonlinear relationship between mean inhibin level and mean FSH and LH level was seen. The inverse value for inhibin correlated with FSH (r = 0.74, p < 0.01) and with LH (r = 0.81, p < 0.01). In conclusion, our results suggest that inhibin is a factor involved in the control of gonadotropin secretion in boys, at least in the pubertal period.

Adolescent↗

PubMed1993

Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens.

Efforts to develop a hormonal contraceptive regimen for men have focused on administration of testosterone (T), alone or together with other agents. Previous regimens have successfully induced azoospermia in only 50-70% of subjects, however. GnRH antagonists, alone or in combination with T, have been shown to induce azoospermia in a very high percentage of nonhuman primates. We tested the hypothesis that the addition of a GnRH antagonist to a high-dose T regimen would lead to a higher percentage of men developing azoospermia than would T alone. We administered the GnRH antagonist, Nal-Glu (100 micrograms/kg.day sc), plus T enanthate, 200 mg im weekly or placebo sc injections daily plus T enanthate, 200 mg im weekly, to separate groups of healthy men for 16-20 weeks. Seven of 10 men who received Nal-Glu plus T and 6 of 9 men who received T alone became azoospermic; gonadotropin levels were suppressed and T levels were increased similarly in both groups. There was a trend toward higher pretreatment gonadotropin levels and lower sperm counts in men who became azoospermic. Weight gain, development of acne, and increases in hematocrit and hemoglobin were similar in the two groups. In the majority of the men, sperm counts returned to the baseline levels within 4-5 months after treatment ended. We conclude that with the dosages of Nal-Glu and T we used in this study, the addition of GnRH antagonist to a high-dose T regimen does not increase the ability of T to suppress spermatogenesis in healthy men. Use of a higher dose of Nal-Glu, a lower dose of T, delaying the start of T replacement until several weeks after Nal-Glu injections are initiated, or prolonged hormonal administration might lead to a combination regimen that will suppress spermatogenesis more fully than does T alone.

Adult↗

PubMed1992

Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels.

OBJECTIVE: To investigate the role of physiologic levels of testosterone in the control of lipoproteins in healthy men. DESIGN: A double-blind, randomized study. SETTING: A university community. PARTICIPANTS: Fifteen healthy men, ages 20 to 36 years. INTERVENTION: We induced acute, reversible hypogonadism in five normal men by administering daily subcutaneous injections of the gonadotropin-releasing-hormone (GnRH) antagonist, Nal-Glu, for 6 weeks. Another group of five normal men received Nal-Glu plus weekly injections of testosterone enanthate, 100 mg/wk, thereby maintaining normal serum testosterone levels. Five additional men received placebo injections. MEASUREMENTS: Plasma lipids, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, apoprotein A1, and serum levels of gonadotropins, estradiol, and testosterone were measured before, during, and after treatment. RESULTS: At the end of the treatment period, HDL cholesterol levels in men receiving Nal-Glu increased by 26% (95% CI, 18% to 34%; P less than 0.05). Levels of HDL2, HDL3, and apoprotein A1 increased by 63% (CI, 16% to 110%), 17% (CI, 3% to 31%), and 17% (CI, 5% to 29%), respectively (P less than 0.05 for each parameter). Total cholesterol increased by 12% (CI, 2% to 22%). Low-density lipoprotein (LDL) cholesterol and triglyceride concentrations did not change. No statistically significant changes occurred in any lipid measurement in men receiving Nal-Glu plus androgen replacement or placebo (P greater than 0.05). CONCLUSIONS: Experimental hypogonadism induced by administration of a GnRH antagonist results in a statistically significant increase in HDL cholesterol, including HDL2 and HDL3. These effects are most likely due to decreased androgen levels because they are reversed by administration of antagonist together with testosterone. Our results imply that androgen levels in the normal adult male range have a suppressive effect on HDL cholesterol concentration and may contribute to the increased risk for coronary artery disease in men.

Adult↗

PubMed1992

Onset and characteristics of the midcycle surge in bioactive and immunoactive luteinizing hormone secretion in normal women: influence of physiological variations in periovulatory ovarian steroid hormone secretion.

Limited studies in nonhuman primates suggest that the midcycle LH surge is characterized by distinctly different patterns of bioactive (LH-BIO) and immunoactive (LH-RIA) LH secretion. To further examine the patterns of midcycle LH-BIO and LH-RIA secretion and explore the influence of physiological variations in steroid hormone feedback on LH surge dimensions we studied seven normal ovulatory women over the periovulatory interval. In each, blood samples were obtained every 3 h and transvaginal ultrasonography was performed every 12 h over a 5-7 day interval at midcycle. Serum levels of LH-RIA, FSH, estradiol (E2), progesterone (P4), and 17-hydroxyprogesterone were determined by RIA; LH-BIO was estimated using a mouse leydig cell bioassay. Hormone data were standardized to the time of surge onset in LH-RIA (time zero), defined as a 100% increase above a 6-point running mean baseline value; surge cessation was defined as a decline to below baseline concentration. Mean LH-RIA surge duration was 54.0 +/- 4.0 h. LH-BIO surge onset was simultaneous with that of LH-RIA and coincident with the peak in E2 levels (mean data). Mean P4 and 17-hydroxyprogesterone rose in a parallel, phasic manner, an abrupt increase in slope occurred between -6 h and +30 h but an acute rise in P4 was not consistently observed among individuals. The surge onset to follicle rupture interval (mean 37.6 +/- 4.2 h) positively correlated with peak LH-RIA (r = 0.76, P less than 0.05), surge amplitude (r = 0.74, P less than 0.05) and surge onset to peak interval (r = 0.87, P less than 0.02), but not surge duration. There were no significant relationships between E2 or P4 (mean, peak, integrated, slope) and surge amplitude or duration (LH-RIA, FSH), peak value, or surge onset to peak interval (LH-RIA, LH-BIO, FSH). These data suggest that in women, 1) onset of the midcycle surge in LH-RIA and LH-BIO is simultaneous, and 2) surge characteristics are not influenced by physiological variations in steroid hormone secretion that occur beyond the thresholds required for surge initiation.

Adult↗

PubMed1991

The induction of premature luteolysis in normal women--follicular phase luteinizing hormone secretion and corpus luteum function in the subsequent cycle.

Women with luteal phase deficiency have been shown to have an increased frequency of luteinizing hormone pulses in the early follicular phase of the menstrual cycle. Because progesterone is known to modulate luteinizing hormone secretion, it has been hypothesized that the decreased progesterone secretion in a previous luteal phase deficiency cycle could lead to the abnormal luteinizing hormone secretory pattern in the ensuing early follicular phase. With the possibility that the higher luteinizing hormone pulse frequency might lead to another deficient luteal phase, it becomes conceivable that luteal phase deficiency could be self-perpetuating. To test this hypothesis, luteal phase deficiency was induced in six normal women by decreasing luteinizing hormone support of the corpus luteum with a gonadotropin-releasing hormone antagonist Nal-Glu, administered twice daily beginning in the midluteal phase after a control cycle. During the antagonist-treated luteal phase, each subject met the predetermined criteria for induced luteal phase deficiency: a 33% or greater decrease in integrated progesterone from the control cycle and an integrated progesterone level less than 100 ng/ml per day. Luteinizing hormone secretion patterns were determined by frequent blood sampling performed every 10 minutes for 12 hours in the early follicular phase of the control cycle and the cycle after antagonist administration. Daily luteal progesterone levels were measured in the control, treatment, and posttreatment cycles. Each volunteer served as her own control. Standard parameters were compared between the control and posttreatment pulse studies in the early follicular phase: (1) luteinizing hormone pulse frequency was 9.5 +/- 1.0 vs 10.0 +/- 0.9 pulses/12 hours, control vs posttreatment, respectively, p = 0.5; (2) luteinizing hormone pulse amplitude was 11.0 +/- 1.3 vs 12.0 +/- 2.2 ng/ml, p = 0.6; and (3) luteinizing hormone mean level was 19.4 +/- 2.3 vs 22.2 +/- 3.3 ng/ml, p = 0.1. Corpus luteum function was also compared between the control and posttreatment cycles. Luteal phase length was 13.7 +/- 0.6 vs 12.7 +/- 0.6 days, p = 0.08. Integrated progesterone values were 136.9 +/- 12.9 vs 130.5 +/- 11.3 ng/ml per day, p = 0.5. Therefore no discernible abnormalities in early follicular luteinizing hormone secretions or corpus luteum secretion of progesterone occurred after an induced luteal phase deficiency cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1991

Circadian rhythm of serum immunoreactive inhibin in young and elderly men.

Serum testosterone (T) levels and inhibin levels decline with normal male aging. In addition, in young men, serum T levels demonstrate a circadian variation that is blunted or lost with normal aging. The purpose of this study was to determine whether serum immunoreactive inhibin levels also demonstrate a circadian variation in young men and if normal aging has an effect on the 24 hr serum inhibin pattern. Hourly blood samples were obtained for 24 hr from 7 young (age 25-35 yr) and 7 elderly (age 65-72 yr) healthy men. Serum inhibin and testosterone levels were measured by RIA. Similar to T, serum inhibin levels demonstrated a circadian pattern in young men. Elderly men also demonstrated a circadian rhythm in serum inhibin, with an average amplitude that was not significantly different from that found in young men, despite the fact that the average 24-hr inhibin level in the elderly men was significantly lower than in the young men. These results demonstrate that immunoreactive inhibin, like T, displays a circadian rhythm in the serum of adult men and the inhibin biorhythm is maintained in elderly men.

Adult↗