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Biomedical subjects

J M Kaufman

Publications and source records attributed to J M Kaufman.

At least 91 records · Page 5Linked to original sources
PubMed1994

Opioidergic modulation of in vitro pulsatile gonadotropin-releasing hormone release from the isolated medial basal hypothalamus of the male guinea pig.

Endogenous opiates exert a tonic restraint on LH release, which is centrally mediated through inhibition of hypothalamic GnRH secretion. The aim of the present study was, using an in vitro superfusion approach, to perform a detailed study of the effects of opioid receptor activation and blockade on the dimensions of pulsatile GnRH release from the isolated medial basal hypothalamus of the adult male guinea pig. The mu-receptor antagonist naloxone at 10(-3) M (n = 12), 10(-6) M (n = 12), and 10(-9) M (n = 12), the opioid agonist morphine sulfate at the same concentrations (n = 14 for each concentration), or morphine and naloxone together at 10(-3) M (n = 14), was added to the medium alternately either during the first or the second of two consecutive 3-h observation periods. Five-minute fractions (750 microliters) were collected for measurement of GnRH by RIA. Morphine suppressed total GnRH output from the medial basal hypothalami (P < or = 0.01 at 10(-3) M and 10(-6) M; P = NS at 10(-9) M), with mean pulse frequency, mean amplitude of all pulses, and mean sum of pulse amplitudes being significantly inhibited at all morphine concentrations, whether pulse analysis (Ultra pulse analysis algorithm) was performed at a two-coefficient of variation (2CV; P < or = 0.05, P < or = 0.01, and P < or = 0.01, respectively) or a 3CV (P < or = 0.05, P < or = 0.05, and P < or = 0.01, respectively) threshold. A different set of experiments (n = 14), with exposure to 10(-3) M morphine during the second of three consecutive 3-h observation periods, indicated that after morphine withdrawal a gradual recovery of GnRH output and pulse frequency to pretreatment values occurred, whereas pulse amplitude remained significantly suppressed during the posttreatment observation period. The inhibitory actions of 10(-3) M morphine were effectively prevented by the presence of 10(-3) M naloxone. Total GnRH output (P < or = 0.05), mean pulse frequency (P < or = 0.05), mean amplitude of all pulses (P < or = 0.05), and mean of the sum of pulse amplitudes (P < or = 0.01) were increased during opioid blockade with 10(-3) M and 10(-9) M naloxone (either 2CV or 3CV threshold for pulse analysis). A similar trend for 10(-6) M naloxone was only apparent after the exclusion of two outliers with unusually high basal GnRH release.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Pathogenesis of the decreased androgen levels in obese men.

In obese men, sex hormone-binding globulin levels (SHBG) as well as total plasma testosterone (T) levels are decreased. Data concerning the levels of nonprotein-bound testosterone (FT) are discordant, with some researchers reporting normal levels, and other reporting decreased levels. The latter imply an impairment of the feedback regulation mechanism of FT levels. We investigated whether an eventual decrease in FT levels and, hence, functional impairment of the gonadostat might occur only at a more severe degree of obesity than that required for a decrease in SHBG and total T levels. We, therefore, determined androgen and precursor levels in three groups of male subjects: nonobese controls [body mass index (BMI), G (kg)/L2 (m) < 26; n = 70]; moderately (BMI, 30-35; n = 18), and severely (BMI, > 40; n = 22) obese men, respectively. In a subgroup of these controls, moderately and severely obese subjects, respectively, we studied LH levels as well as LH pulsatility. Moreover, as a decrease in FT levels might affect the metabolic pattern of the androgens and, more specifically, 5 alpha-reductase activity, we determined the plasma levels of the major 5 alpha-reduced metabolites, androstanediol glucuronide and androsterone glucuronide (AG), as well as the urinary excretion of the major 5 alpha (androsterone glucuronide) and the major 5 beta (etiocholanolone glucuronide) metabolite of the androgens. In moderately obese men, T levels were decreased, which was the consequence of the decreased SHBG-binding capacity. FT levels, however, were normal as were LH levels and both pulse amplitude and frequency of LH pulses, suggesting a normal hypothalamic control of LH secretion. In severely obese men (BMI, > 40), total T, FT, and LH levels as well as LH pulse amplitude were decreased, indicating a functional impairment of the gonadostat. Even in massively obese subjects with decreased FT levels, androgen metabolism and 5 alpha-reductase activity appeared to be normal, as suggested by similar androstanediol glucuronide and AG levels, determined by RIA or calculated from the conversion rates of precursors obtained in nonobese subjects. This was confirmed by the similar AG/eticholanolone glucuronide ratios in obese and nonobese men.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

Adult↗
PubMed1994

Total amounts of circulating human chorionic gonadotrophin alpha and beta subunits can be assessed throughout human pregnancy using immunoradiometric assays calibrated with the unaltered and thermally dissociated heterodimer.

The aim of the present study was to determine the variations in the balance between total (free plus combined) circulating alpha and beta subunits of human chorionic gonadotrophin (hCG) throughout human pregnancy. The equivalence between the International Units (IU) of hCG (IRP 75/537) and those assigned to the alpha (IRP 75/569) and beta (IRP 75/551) free subunits was experimentally determined by using intact and thermally dissociated hCG. Heat exposure (2 min at 100 degrees C) of hCG preparations resulted in a complete dissociation of hCG into free, soluble and intact alpha and beta subunits. The hCG and alpha and beta subunit contents of unaltered and heated hCG preparations were assessed by specific immunoradiometric assays. The amount of immunoreactive subunits dissociated by heat from hCG could then be evaluated on a molar basis. Circulating hCG and its free alpha and beta subunits were immunoassayed in 836 blood samples collected from healthy pregnant women at different gestational ages. After conversion of hCG and its subunits into a common IU system, the gestational profiles of the total amounts (free plus combined) of alpha- and beta hCG subunits increased together and peaked at 9-10 weeks of gestation. Thereafter, total alpha and beta subunits decreased and subsequently remained stable until term. The decline in total alpha hCG subunit was less marked than that of total beta hCG subunit. The alpha- to beta hCG ratio was equimolar until 10 weeks of gestation when it increased almost fourfold until term (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗
PubMed1994

Case management in a vertically integrated health care system.

A comprehensive case management system has been developed at Fallon Healthcare System, with overall aims of improving medical, social and financial outcomes for health plan members who need complex patient care management. A definition of case management is offered, goals of case management services are specified, criteria for appropriate referrals are outlined, and the process of implementing services is described. Formal evaluation of the program is being planned.

Age Factors↗
PubMed1993

Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension.

In a group of 36 untreated patients with mild-to-moderate essential hypertension (office systolic blood pressure [SBP] 160 +/- 3.4 mm Hg, office diastolic blood pressure [DBP], 102 +/- 1.5 mm Hg), 24-hour ambulatory blood pressure monitoring, and determination of left ventricular (LV) mass index according to the formula of Devereux were performed. After an overnight fast, blood samples were taken for the determination of serum aldosterone levels and plasma renin activity. Urinary catecholamine concentrations were assayed from 24-hour urine collections. Left ventricular mass index (143.7 +/- 8 g/m2) did not correlate significantly with either office SBP or office DBP. The correlation of LV mass index with mean 24-hour SBP (145 +/- 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour DBP (90 +/- 3 mm Hg) with r = 0.499 (p = 0.004). Urinary catecholamine levels did not correlate with LV mass index. In addition, LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050) and serum aldosterone levels (r = 0.559, p = 0.0009). There was a strongly significant correlation between LV mass index and serum aldosterone levels even after adjustment for mean 24-hour SBP (r = 0.496, p = 0.005) and DBP (r = 0.514, p = 0.004). These results demonstrate that ambulatory blood pressure determinations but not office blood pressure parameters correlate well with left ventricular hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of left ventricular mass as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Evaluation of erectile dysfunction by dynamic infusion cavernosometry and cavernosography (DICC). Multi-institutional study.

In a cooperative, private practice, multi-institutional impotence study, dynamic infusion cavernosometry and cavernosography (DICC) was performed on 743 patients to make an accurate diagnosis and/or identify candidates for penile revascularization. Maximum equilibrium intracorporeal pressure achieved following papaverine and phentolamine injection (Phase I) averaged 29.42 +/- 0.76 mm Hg, approximately one third of normal erection pressure. Corporeal pressure fall from 150 mm Hg over thirty seconds (cavernosometry) averaged 82.38 +/- 1.33 mm Hg (Phase II). The gradient between systolic and cavernosal artery pressure averaged 42.84 +/- 1.12 mm Hg on the right and 43.33 +/- 1.13 mm Hg on the left (Phase III). Cavernosography at 90 mm Hg erection pressure was performed in Phase IV. Of the 124 patients from one center who were reviewed in greater detail, pure cavernosal artery insufficiency (CAI) was found in 25 (20.2%), corporeal veno-occlusive dysfunction (CVOD) in 26 (21.0%), and 73 patients (58.9%) demonstrated combined CAI and CVOD. Diabetics (n = 69) achieved lower equilibrium intracorporeal pressures than nondiabetics, had similar CVOD, and worse CAI. Smokers (n = 365) and patients with Peyronie's disease (n = 32) had erectile dysfunction similar to those without these conditions. Patients impotent after trauma (n = 124) were younger, achieved higher intracorporeal pressures, and showed better corporeal veno-occlusive function than those without trauma. Complications of DICC were minimal and infrequent. After DICC, 169 patients underwent internal pudendal arteriography, 105 had arterial bypass surgery with or without penile venous ligation procedures, and 45 had venous surgery alone. Dynamic infusion cavernosometry and cavernosography is a useful erectile function study to evaluate impotence and can be performed easily in a private practice setting.

Blood Pressure↗
PubMed1993

Early experience with the first pre-connected 3-piece inflatable penile prosthesis: the Mentor Alpha-1.

The aim of this clinical investigation was to obtain preliminary treatment outcome data concerning the Mentor Alpha-1, the first 3-piece inflatable penile prosthesis with pre-connected tubing between the pump and the penile cylinders. The study was designed to be the first multi-institutional treatment outcome report for any clinically available penile prosthesis with data analysis to be independent of the participating surgeons. A total of 12 board-certified urologists of mixed surgical training backgrounds and practices implanted the Alpha-1 device in 112 consecutive patients. With a mean of 27 +/- 5 months of followup the surgical complication rate included a 4% mechanical malfunction, 2% infection rate and 9% reoperation rate. Patient experience with the implanted device was computed from information on 96 of the 112 patients who returned a questionnaire. Of the patients 82% stated that the device fulfilled expectations as a treatment for impotence and 83% had improved sexual intercourse by 8 weeks after implantation. Patient satisfaction was computed on a scale of 12 equally weighted interrelated variables. Of the patients 77% recorded 9 or more cumulative satisfaction points. Patient and physician questionnaire data were analyzed for their relation to the cumulative prosthesis satisfaction score. A significant difference in cumulative scores was found for physician reported long-term postoperative problems (mean satisfaction score 8.1 for patients with problems versus 10.2 for patients without problems, p = 0.018). The Alpha-1, with its feature of pre-connected tubing, is a reliable 3-piece inflatable penile prosthesis associated with a high level of patient satisfaction.

Data Collection↗
PubMed1993

Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males.

OBJECTIVE: In view of the fact that GH-deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH-deficient adult males. DESIGN: We performed a 6-month randomized, double-blind, placebo-controlled study, followed by 12-24 months of GH treatment in all patients. PATIENTS: Twenty adult males with GH deficiency of childhood onset were studied. MEASUREMENTS: We measured serum IGF-I, serum phosphate, biochemical indices of bone turnover (serum alkaline phosphatase activity, serum osteocalcin, serum carboxyterminal propeptide of type-I procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios) and bone mineral content, measured at the forearm and the lumbar spine by single and dual-photon absorptiometry respectively. RESULTS: After 3 and 6 months of GH administration, the serum levels of alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type-I procollagen, and the fasting urinary hydroxyproline/creatinine ratio were significantly increased compared to placebo-treated patients (P < 0.01 to P < 0.001). During the open study phase, the values for these indices of bone turnover remained elevated above pretreatment levels (P < 0.01 to P < 0.001 at 12 months), a downward trend becoming apparent after about one year of GH treatment. BMC values showed an initial decline after 3 months of GH treatment (most likely due to an expansion of the remodelling space), followed by a significant and progressive increase above pretreatment values, reaching 7.8% for total BMC at the lumbar spine (L2-L4) and 9.9% for total BMC at the forearm, after 30 months of GH administration. CONCLUSIONS: The data of our study show that administration of substitutive doses of growth hormone to GH-deficient adult males activates bone turnover for a period of at least one year and suggests that this may have a beneficial effect on bone mass in these patients.

Adult↗
PubMed1993

Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men.

To evaluate the effects of obesity on the hypothalamo-pituitary-testicular axis, we compared total and free (FT) testosterone (T), androstenedione, dehydroepiandrosterone and its sulfate, and 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide, and estradiol levels in a group of 35 obese [body mass index (BMI), > 30] men (aged 17-61 yr) to levels in a nonobese control group. We observed a highly significant negative correlation (P < 0.001) between plasma (F)T levels and BMI and a significant positive correlation (P < 0.01) between E2 levels and BMI. There were no differences between the obese and the nonobese men in levels of androstenedione, dehydroepiandrosterone sulfate, and 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide. Insulin levels were significantly higher in obese men and were significantly (P < 0.02) correlated with the waist hip girth ratio. To evaluate the role of the hypothalamo-pituitary complex in the decreased (F)T levels in obese men, diurnal (0800-2000 h) LH pulsatility was studied in eight obese middle-aged men and eight age-matched controls. The pulsatility of plasma cortisol levels was also studied. Whereas LH pulse frequency was similar in the obese and control subjects, mean diurnal LH levels, mean diurnal LH pulse amplitude, and the sum of all diurnal LH pulse amplitudes and secretory masses were significantly lower in the obese than in the controls. Moreover, there was a highly significant correlation between the sum of LH pulse amplitudes and plasma (F)T levels. This decrease in LH pulse amplitude is not an isolated phenomenon of hypothalamo-pituitary dysfunction in obese men, because the pulse amplitude of plasma cortisol levels was also decreased. The decreased LH pulse amplitude together with the normal respond of Leydig cells to hCG stimulation reported in the literature suggest by inference that the decreased FT levels in obese men are the consequence of a hypogonadotropism. The decreased LH pulse amplitude and the decreased amplitude of cortisol pulses, and hence probably of ACTH pulses, point toward a general alteration of hypothalamo-pituitary function in obese men.

Adolescent↗
PubMed1992

Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset.

In order to determine whether growth hormone (GH) deficiency of childhood onset affects the adult bone mineral status, we assessed bone mineral content (BMC) by photon absorptiometry in 30 full-grown GH-deficient men (8 with isolated GH deficiency and 22 with multiple pituitary deficiencies; 28 previously treated with GH) and in 30 male controls matched for age (within 4 yr) and height (within 10 cm). Forearm BMC was measured by single photon absorptiometry just proximally of the distal one third of the nondominant forearm (PBMC-2 in arbitrary units and PBMC/bone width (BW) after normalization for bone width) and at a more distal site, close to the carpal joint (DBMC-2 and DBMC/BW). Lumbar BMC was measured by dual photon absorptiometry and reported as total BMC for L2-L4 (LBMC in g) and after normalization for projected area (LBMD in g/cm2). The patients had a significantly lower BMC, both at the forearm (P less than 0.0001) and at the lumbar spine (P less than 0.005): 35.7 +/- 1.0 vs. 50.0 +/- 1.6 and 36.9 +/- 1.2 vs. 52.8 +/- 1.9 (mean +/- SEM) for PBMC-2 and DBMC-2 in patients and controls, respectively; 1.36 +/- 0.03 vs. 1.70 +/- 0.04 and 1.07 +/- 0.03 vs. 1.35 +/- 0.04 for PBMC/BW and DBMC/BW; 34.00 +/- 1.08 vs. 42.02 +/- 1.27 g for LBMC and 0.886 +/- 0.016 vs. 0.976 +/- 0.018 g/cm2 for LBMD. Both the patients with isolated GH deficiency and the patients with multiple pituitary deficiencies were osteopenic when compared to their respective controls (P less than 0.01 to P less than 0.0001 for the patients with multiple deficiencies; statistical significance reached for PBMC-2, DBMC-2, and DBMC/BW only, P less than 0.05, in the small group of patients with isolated GH deficiency). For the patients (n = 19) who had at least three serial measurements over a period of 6 to 28 months, no decrease in BMC was detected. Our findings indicate that men with GH deficiency of childhood onset present with a low adult bone mass, despite prior GH substitution in most of these subjects. The observations of a more pronounced bone mineral deficit at the forearm (20-30% lower mean values, depending on the type of measurements) than at the lumbar spine (9-19%) and the findings of osteopenia in both the patients with isolated GH deficiency and multiple pituitary deficiencies, support the view that GH deficiency per se is responsible for part of the observed deficit.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Influence of the arterial blood pressure and nonhemodynamic factors on left ventricular hypertrophy in moderate essential hypertension.

In a group of 36 untreated patients with mild to moderate essential hypertension (office systolic and diastolic blood pressures (BPs) 160 +/- 3.4 and 102 +/- 1.5 mm Hg, respectively), a 24-hour ambulatory BP monitoring and determination of left ventricular (LV) mass index according to the formula of Devereux were performed. After an overnight fast, blood samples were taken for the determination of serum aldosterone, plasma renin activity and serum parathyroid hormone. Urinary catecholamines were sampled for 24 hours. LV mass index (143.7 +/- 8 g/m2) did not correlate significantly either with office systolic or diastolic BP. The correlation of LV mass index with mean 24-hour systolic BP (145 +/- 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour diastolic BP (90 +/- 3 mm Hg) with r = 0.500 (p = 0.004). Urinary catecholamines were not correlated with LV mass index. LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050), and aldosterone (r = 0.559, p = 0.001). There was a very significant correlation between LV mass index and parathyroid hormone (r = 0.719, p = 0.00001) even after adjustment for mean 24-hour systolic and diastolic BPs. These results clearly demonstrate that ambulatory BP determinants but not office BP parameters are well correlated with LV hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of LV mass as well. Besides the renin-angiotensin-aldosterone system, parathyroid hormone appears to play an important role in cardiac hypertrophy.

Adult↗
PubMed1991

Influence of nonhemodynamic factors on the microcirculation in moderate arterial essential hypertension.

This study is aimed at examining the role of non-hemodynamic factors on the impaired microcirculation in patients with moderate essential hypertension. In a series of 31 patients (mean age, 47.8 +/- 1.1 years) with newly diagnosed untreated moderate essential hypertension (mean systolic blood pressure 161.7 +/- 2.0 mm Hg, mean diastolic blood pressure 102.4 +/- 1.5 mm Hg), parameters of the capillaroscopic examination of the finger microcirculation (mean number of capillaries, NRCAP), length of the capillaries (LECAP, microns), diameter micron) of the efferent (EFDI) and afferent (AFDI) apillaries, and mean red blood cell velocity (RBCV, microns/sec), which was measured by the flying spot technique, were correlated with a number of hormones (sampled after an overnight fast) including: plasma renin activity, aldosterone, and parathyroid hormone (PTH). A significant correlation (P less than .05) could be obtained between several parameters of the microcirculation and PTH:PTH (23.8 +/- 1.4 pg/mL)-NRCAP (14.9 +/- 0.5): r = -0.440, P = .013; PTH-AFDI (4.0 +/- 0.5 microns): r = 0.442, P = .012; PTH-EFDI (2.8 +/- 0.5 microns): r = 0.416, P = .019; PTH-RBCV (711 +/- 69 microns/sec): r = -0.351, P = .05. Furthermore, 24-h urinary norepinephrine (U-NOR) and afferent and efferent diameter of the capillaries intercorrelated significantly: U-NOR (46.0 +/- 6.2 micrograms/24 h)-AFDI: r = 0.439, P = .034; U-NOR-EFDI; r = 0.462, P = .025. This study shows that in patients with moderate essential arterial hypertension nonhemodynamic factors have an influence at the level of the microcirculation.

Aldosterone↗
PubMed1991

Permeability of the blood-brain barrier for atenolol studied by positron emission tomography.

The permeability of the blood-brain barrier for atenolol, a hydrophilic beta-adrenergic blocking agent, has been assessed in dogs, by studying the distribution of [11C]atenolol in brain tissue with positron emission tomography. The passage of atenolol into the brain was very limited, but a measurable small net influx into the brain tissues did occur. Osmotic opening of the blood-brain barrier resulted in a marked increase of the atenolol concentrations in brain tissue. The approach described, with sequential non-invasive measurements in brain tissue, is applicable to pharmacokinetic studies of atenolol in man.

Animals↗
PubMed1991

Influence of age on the responsiveness of the gonadotrophs to luteinizing hormone-releasing hormone in males.

The mechanisms that most likely underly the attenuated response of plasma LH to antiopioids or antiestrogens and the reduced frequency of large amplitude LH pulses in elderly men are decreased LHRH release and/or decreased sensitivity of the gonadotrophs to LHRH. To test the latter hypothesis, the LH response, measured both as bioactivity (B) and immunoactivity (IR), to increasing doses of LHRH ranging from 0.625-5 micrograms, administered as an iv bolus, was evaluated in 10 young (20-45 yr old) and 10 elderly (64-78 yr old) monks. Both basal B- and IR-LH levels were significantly higher in elderly men. The maximal response to each dose was similar in young and elderly men when measured as IR-LH, but the B-LH response was higher in elderly men. The B/IR LH ratio increased with increasing LH levels. The mean half-life of plasma IR-LH in the elderly was significantly longer than that in the group of young men and significantly longer than the mean half-life of B-LH. It is concluded that the sensitivity of the gonadotrophs to LHRH is not decreased in elderly men. This suggests that the attenuated response of LH levels to antiopioids and antiestrogens, respectively, as well as the reduced number of spontaneous high amplitude LH pulses in elderly men may, instead, be the consequence of the release of a decreased mass of LHRH at each pulse.

Adult↗