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S Bhasin

Publications and source records attributed to S Bhasin.

18 recordsLinked to original sources
PubMed1992

Developments in the control of testicular function.

Clinicians and clinical investigators have developed improved means for controlling testicular function in men. New and refined approaches for stimulation and inhibition of the hypothalamic-pituitary-testicular axis are now available. This chapter reviewed the most successful ways to inhibit the reproductive axis in men and its current application to the treatment of precocious puberty, metastatic prostate cancer, benign prostate hyperplasia and as prospective male contraceptives. Safe, effective and reversible medical approaches to male contraception are now approaching reality. Azoospermia and severe oligozoo/azoospermia can now be accomplished in the majority of men with combined GnRH antagonists and replacement doses of testosterone. Androgens and androgen-progestogen concentrations will induce azoospermia in over 90% of Asian men and azoospermia or severe oligospermia in Caucasian ethnic groups. Field trials are ongoing to determine whether testosterone administration will be more effective than condoms as contraceptives. True precocious puberty can now be managed more effectively than in the past by suppression of gonadotropin secretion with GnRH analogues. Precocious puberty due to other causes can be treated more effectively with inhibitors of steroidogenesis and blockers of androgen action. Metastatic prostate cancer, previously treatable with either castration or oestrogens, is now amenable to suppression of androgen secretion. GnRH analogues are given either alone or combined with blockers of androgen action. While significant palliative effects are observed with endocrine ablative therapy in most men with Stage C or D prostate cancer, modest increases in duration of survival may be seen. Benign prostate hyperplasia was previously approachable only with surgical intervention. Recent data have suggested that medical treatment with 5 alpha-reductase inhibitors and/or selective alpha-adrenergic blockers may offer non-surgical alternatives in some patients. More data are needed to determine the role of medical management of this common disorder.

5-alpha Reductase Inhibitors↗
PubMed1992

A biodegradable testosterone microcapsule formulation provides uniform eugonadal levels of testosterone for 10-11 weeks in hypogonadal men.

Limitations of presently available testosterone esters (enanthate and cypionate) include the fluctuating serum testosterone levels and the need for relatively frequent injections (every 10-21 days). These limitations of testosterone esters have prompted the development of more physiological and longer acting systems for androgen delivery. This paper reports pharmacokinetic and pharmacodynamic data with a second generation long-acting testosterone microcapsule formulation in hypogonadal men. This was a single dose, open label, nonrandomized study. Ten hypogonadal men with primary (n = 6) or secondary (n = 4) hypogonadism, otherwise in good health, received 630 mg microencapsulated testosterone in dextran solution (IM) on day 1. Serum total and free testosterone; LH; FSH; dihydrotesterone; estradiol; sex hormone-binding globulin; total cholesterol; high, low, and very low density lipoprotein cholesterol; triglycerides; and apoprotein-AII and -B were measured on multiple occasions during the 2-week control period and the 16-week treatment period. In addition, on days 0, 1, 28, 56, and 84, subjects were hospitalized for detailed hormone analyses over the 24-h period. Serum total and free testosterone levels rose quickly into the midnormal range and stayed uniformly in the eugonadal range for about 70-77 days, after which serum testosterone levels declined gradually into the hypogonadal range. Testosterone release from the microcapsule formulation over the first 10 weeks approximated zero order kinetics. Serum dihydrotestosterone levels rose into the normal range, and testosterone to dihydrotestosterone ratios remained in the physiological range. Serum estradiol levels rose and stayed in the midnormal male range. Serum sex hormone-binding globulin levels decreased significantly during treatment. Serum LH and FSH levels also significantly decreased in the six hypergonadotropic men. Total cholesterol low and very low density lipoprotein cholesterol and triglyceride levels did not change, but plasma high density lipoprotein cholesterol levels decreased significantly during treatment. These data indicate that testosterone microcapsule formulation provides uniform eugonadal levels of testosterone for about 10 weeks. The long duration and zero order kinetics make it an attractive alternative to existing methods of androgen replacement.

Adolescent↗
PubMed1992

Induction of azoospermia in normal men with combined Nal-Glu gonadotropin-releasing hormone antagonist and testosterone enanthate.

The effects of a combined GnRH antagonist and testosterone (T) replacement regimen on gonadotropins and spermatogenesis were examined to assess its potential as a male contraceptive regimen. The potent Nal-Glu GnRH antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5, D4-p-methoxybenzoyl-2-amino butyric acid6,D-Ala10]GnRH) was administered daily (7.5 mg, sc) to eight normal men for 16 weeks. T enanthate was given im starting at week 2 and every 2 weeks thereafter through week 14 of the treatment phase. Serum LH, FSH, T, and estradiol concentrations were measured frequently during the 5-week control period, the 16-week treatment phase, and the 14-week recovery phase. Semen analyses were performed every week during the control phase and every 2 weeks during the treatment and recovery phases. Seven of eight subjects became azoospermic by 6-10 weeks of treatment; the eighth subject, who failed to achieve azoospermia, suppressed his sperm count to 7 million/mL by week 14 (from a mean baseline of 42 million/mL) before treatment was prematurely terminated because of localized swelling at each of his injection sites. Sperm counts returned to baseline 10-14 weeks after the end of Nal-Glu administration. Seven of the eight subjects showed suppression of LH to the limit of assay detection (less than 0.2 U/L), whereas the eighth subject showed incomplete suppression. Serum bioactive and immunoreactive LH concentrations showed concordant responses. Mean serum FSH concentrations were also markedly suppressed. Serum T and estradiol concentrations declined dramatically during the first 2 weeks of Nal-Glu GnRH treatment, but returned to the normal physiological range after T enanthate replacement was initiated. Libido and sexual potency were maintained. No systemic side-effects, other than erythema and induration at injection sites, were observed. These data demonstrate that combined GnRH antagonist plus T treatment can predictably and reversibly induce azoospermia in most men and has potential as a male contraceptive regimen.

Adult↗
PubMed1992

Effect of improved assay sensitivity on luteinizing hormone pulse detection after gonadotropin-releasing hormone antagonist treatment in man.

When serum levels of a hormone are at or below the detection limit of the measurement system, accurate characterization and quantitation of pulsatile hormone secretion may be difficult. This point is well illustrated in this study, which used two immunoassays with markedly different assay sensitivities to quantitate pulsatile LH secretion in men in whom serum LH levels had been suppressed by the administration of a GnRH antagonist. Five normal men received 5 mg Nal-Glu, sc, daily for 21 days. Blood was drawn at 10-min intervals over 8 h on days 0 and 21. Samples were assayed in triplicate in both a conventional LH RIA with a sensitivity of 0.6-1.0 IU/L and a two-site-directed ultrasensitive immunofluorometric assay (IFMA) with assay sensitivity ranging from 0.05-0.125 IU/L. LH pulses were analyzed by Cluster analysis (C) and were corroborated by the Detect algorithm (D). Nal-Glu suppressed LH (C) pulse amplitude from 4.0 +/- 0.7 to 0.40 +/- 0.03 IU/L by LH RIA and from 7.8 +/- 2.1 to 0.21 +/- 0.04 IU/L by LH IFMA. An apparent reduction in LH pulse number was observed in the RIA data on day 21 by both pulse detection methods [4.2 +/- 0.4 vs 2.4 +/- 0.2/8 h on days 0 and 21 by C (P < 0.005); 5.8 +/- 0.8 vs. 2.8 +/- 0.7 by D (P < 0.05)]. However, the IFMA measurements in the same samples using the more sensitive LH IFMA showed no difference in pulse number between days 0 and 21. The RIA data correlated well with the IFMA data, with a concordance coefficient ranging from 0.66-0.9. In summary, the Nal-Glu GnRH antagonist markedly decreases LH pulse amplitude, but not pulse frequency. These observations are consistent with competitive inhibition of GnRH action at the pituitary site by the Nal-Glu antagonist; they indicate that assay characteristics can significantly affect quantitation of hormone pulse pattern and underscore the need for ultrasensitive LH assays for accurate assessment of LH pulse characteristics when LH levels are low or suppressed.

Adult↗
PubMed1991

Knowledge amongst adolescent girls about nutritive value of foods and diet during diseases, pregnancy and lactation.

Knowledge about nutritive value of food, diet during diseases and antenatal and postnatal period was assessed amongst 152 adolescent school girls. A total of 23.69 and 55.93% students had incorrect knowledge that pulses and non-vegetarian foods should be avoided during later half of the pregnancy. A total of 63.82, 66.45 and 71.72% of subjects had incorrect knowledge that almonds have more nutritive value than groundnuts, fruits are rich sources of calories and desi ghee has more nutritive value than vanaspathi, respectively. Majority (90.78%) had correct knowledge that obesity is caused due to excess intake of calories than required by an individual and low iron content and poor availability of iron from food is a major cause of anemia in mothers and children.

Adolescent↗
PubMed1991

Assessment of knowledge and skills about growth monitoring amongst multipurpose workers in an ICDS project.

Knowledge and skills amongst 34 multipurpose workers working in an ICDS project about growth monitoring was assessed using interview technique. All workers had correct knowledge about rationale of growth monitoring. A total of 73.5% and 94.1% had knowledge that flattened growth curve indicates no weight gain and descending growth indicates decrease in weight, respectively.

Body Weight↗
PubMed1991

Marked suppression of gonadotropins and testosterone by an antagonist analog of gonadotropin-releasing hormone in men.

To study the dose response characteristics of a gonadotropin-releasing hormone (GnRH) antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5,dGlu6 (AA), d-Ala10] GnRH; Nal-Glu), 1.5 or 5.0 mg of Nal-Glu were administered to two groups of five normal men by daily subcutaneous injection for 21 days. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were determined on multiple occasions before, during, and after the antagonist treatment. Five milligrams Nal-Glu markedly suppressed mean serum immunoreactive LH to a mean of 1.5 +/- 0.4 IU/L (+/- SEM), immunoreactive FSH to the limit of assay detection (1 IU/L), and lowered basal mean serum T to castrate range (less than 2 nmol/L). Serum bioactive LH levels also showed a marked decrease in the 5.0-mg group similar to that seen in immunoreactive LH levels. Amplitude of immunoreactive LH pulses was markedly reduced in the 5.0-mg group on day 21. A 1.5-mg dose of Nal-Glu transiently suppressed serum immunoreactive LH levels on day 1. There was a subsequent escape on the rest of the days sampled. Serum immunoreactive FSH levels were not significantly changed over the 21-day treatment period. Serum T levels were transiently suppressed only on day 1 paralleling immunoreactive LH suppression. No adverse systemic side effects occurred. Thus, the 5.0-mg dose of this GnRH antagonist provides a pharmacological means of markedly suppressing the hypothalamic-pituitary-gonadal axis and, therefore, has potential as a male contraceptive.

Analysis of Variance↗
PubMed1990

The role of luteinizing hormone in regulation of testicular inhibin alpha and beta-B subunit messenger RNAs in immature and adult animals.

In vivo and in vitro evidence indicates that FSH is a primary regulator of testicular inhibin production. However, recent reports suggest that LH may also promote inhibin secretion in vivo. To investigate whether LH regulates inhibin subunit messenger RNA (mRNA) expression as well, we examined the effects of hypophysectomy and LH replacement on the testicular content of inhibin alpha and beta-B subunit mRNAs in sexually immature and adult rats. Twenty- and 60-day-old intact and hypophysectomized rats received saline or 0.25, 2.5, 25.0, or 250 micrograms ovine LH/100 g body wt sc, twice daily for 7 days beginning on the day after hypophysectomy (n = 5/group in three separate experiments). The inhibin subunit mRNA content of each testis was measured for statistical analysis by dot-blot hybridization, and experimental results were confirmed by northern analysis of poly(A) RNA from each sample. In immature animals, the testicular content of both inhibin subunit mRNAs was decreased after hypophysectomy; inhibin alpha and beta-B mRNA levels were decreased to 6.9 +/- 0.9% and 31.7 +/- 2.7% of intact control values, respectively. In adult animals, hypophysectomy resulted in a more modest decrease in inhibin alpha subunit mRNA per testis (44.9 +/- 3.1% of controls) but had no effect on beta-B subunit mRNA. Replacement of LH to immature hypophysectomized animals did not alter levels of mRNA for either inhibin subunit. However, in adults LH restored testicular inhibin alpha subunit mRNA content in testes of hypophysectomized animals to levels seen in intact, saline-treated control animals. LH replacement also slightly but consistently decreased testicular beta-B subunit mRNA content compared to levels seen in hypophysectomized, saline-treated rats. These results indicate that although the response of inhibin subunit mRNAs to pituitary input decreases as a function of sexual maturation, LH may play an important role in regulation of inhibin subunit mRNA expression in adult but not immature testes. The mechanism(s) of LH action on testicular inhibin subunit gene expression is currently unknown, but may involve either direct actions of LH on Leydig cell inhibin subunit mRNAs or indirect actions of interstitial cell factors on Sertoli cell inhibin subunit gene expression.

Animals↗
PubMed1990

Testosterone regulates the secretion of thyrotrophin-releasing hormone (TRH) and TRH precursor in the rat hypothalamic-pituitary axis.

Orchidectomy has been reported to decrease concentrations of thyrotrophin (TSH) in the circulation of male rats without affecting serum levels of thyroid hormones. To understand the mechanism underlying this observation, we have measured the effect of gonadal status on the in-vitro release of TSH-releasing hormone (TRH) by male rat hypothalamic fragments. Because hormone release rates can be affected by changes in the post-translational processing of the hormonal precursors, we have also studied the corresponding changes in the concentrations of TRH and TRH-Gly, a TRH precursor peptide in hypothalamus and pituitary, by radioimmunoassay. We observed a significant decline in the in-vitro release of TRH from incubated hypothalami 1 week after castration, which was quantitatively reversed by testosterone replacement. Concentrations of TRH and TRH-Gly in the posterior pituitary, on the other hand, which derive from neurones of hypothalamic origin, increased significantly with castration and were returned to the normal range by testosterone replacement. We conclude that the primary effect of testosterone is the stimulation of hypothalamic TRH release, resulting in the depletion of TRH and TRH precursors from TRH-containing neurones which project into the median eminence and posterior pituitary.

Animals↗
PubMed1990

Knowledge and attitude amongst well-to-do adolescent school girls towards breast feeding.

A study was conducted to determine the knowledge and attitude about breastfeeding amongst adolescent school girls (n = 74) studying in an urban public school in Delhi. A pretested semi-structured questionnaire was administered. The majority of respondents had correct knowledge about the age of initiation of breast feeding (76%), introduction of semi-solid foods (61%), feeding of colostrum (58%) and superiority of breast milk over commercial preparations of milk (81%). Most believed wrongly that consumption of dry fruits (89%) and high intake of milk and pure ghee (78%) would increase breast milk secretion. The percentages of girls wrongly believing that breast feeding should be discontinued if mother was suffering from tuberculosis, malaria and diarrhea were 96, 85 and 81 respectively. There is need for including adolescent girls in continuing education activities about maternal and child health.

Adolescent↗
PubMed1989

Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study.

Although there have been anecdotal reports of cardiac toxicity associated with fluorouracil (5-FU) therapy, this phenomenon has not been studied in a systematic fashion. We prospectively performed continuous ambulatory ECG monitoring on 25 patients undergoing 5-FU infusion for treatment of solid tumors in order to assess the incidence of ischemic ST changes. Patients were monitored for 23 +/- 4 hours before 5-FU infusion, and 98 +/- 9 hours during 5-FU infusion. Anginal episodes were rare: only one patient had angina (during 5-FU infusion). However, asymptomatic ST changes (greater than or equal to 1 mm ST deviation) were common: six of 25 patients (24%) had ST changes before 5-FU infusion v 17 (68%) during 5-FU infusion (P less than .002). The incidence of ischemic episodes per patient per hour was 0.05 +/- 0.02 prior to 5-FU infusion v 0.13 +/- 0.03 during 5-FU infusion (P less than .001); the duration of ECG changes was 0.6 +/- 0.3 minutes per patient per hour before 5-FU v 1.9 +/- 0.5 minutes per patient per hour during 5-FU (P less than .01). ECG changes were more common among patients with known coronary artery disease. There were two cases of sudden death, both of which occurred at the end of the chemotherapy course. We conclude that 5-FU infusion is associated with a significant increase in silent ST segment deviation suggestive of ischemia, particularly among patients with coronary artery disease. The mechanism and clinical significance of these ECG changes remain to be determined.

Adult↗
PubMed1989

Regulation of testicular inhibin subunit messenger ribonucleic acid levels in vivo: effects of hypophysectomy and selective follicle-stimulating hormone replacement.

To examine the pretranslational regulation of inhibin subunits in the rat testis by FSH, we studied the effects of hypophysectomy with or without selective FSH replacement on testicular inhibin subunit mRNA levels in immature and adult animals. In the first experiment (Exp I), sexually immature (20-23 days old) intact and hypophysectomized male rats were killed 1, 3, and 7 days after surgery, and the testicular content of inhibin subunit mRNAs was determined by filter hybridization. A second group of immature, intact, or hypophysectomized rats was treated with saline or FSH for 7 days as follows: I) intact, saline; II) hypophysectomized, saline; III) hypophysectomized, FSH [0.05 microgram/100 g BW, sc, twice daily (BID)]; IV) hypophysectomized, FSH (0.50 microgram/100 g BW, sc, BID); V) hypophysectomized, FSH (5.0 micrograms/100 g BW, sc, BID); and VI) hypophysectomized, FSH (50.0 micrograms/100 g BW, sc, BID). In the second experiment (Exp II), adult (60 days old) intact or hypophysectomized animals were treated with saline, FSH, and/or testosterone for 7 days as follows: I) intact, saline; II) hypophysectomized; saline; III) hypophysectomized, 22-mm testosterone implant; IV) hypophysectomized, FSH (50.0 micrograms/100 g BW, sc, BID; and V) hypophysectomized, 22-mm testosterone implant plus FSH (50.0 micrograms/100 g BW, sc, BID. The effects of FSH and testosterone on testicular inhibin subunit mRNA levels were measured by filter hybridization. In Exp I, the level of inhibin alpha-subunit mRNA per testis was significantly lower in hypophysectomized rats than in intact controls at all time points after surgery. Replacement of FSH to hypophysectomized immature rats led to a dose-dependent increase in alpha-subunit mRNA per testis. However, hypophysectomy and FSH replacement had no significant effect on beta-B-subunit mRNA. In adult rats (Exp II), hypophysectomy significantly lowered and FSH replacement increased testicular inhibin alpha-subunit mRNA levels. Replacement of testosterone to adult animals, either alone or in combination with FSH, had no effect on expression of inhibin alpha-subunit mRNA. beta-B mRNA levels in adult testis were not significantly altered by any of the treatments. beta-A-Subunit mRNA levels were below the detection threshold of filter hybridization in both Exp I and II. Collectively, these data demonstrate that FSH regulates alpha- but not beta-B-subunit mRNA in the testis of both immature and adult rats in vivo. Differential regulation of inhibin subunits may provide a mechanism for creation and regulation of functional diversity of inhibin-related peptides in the testis.

Animals↗
PubMed1988

Differential regulation of rat luteinizing hormone alpha- and beta-subunits during the stimulatory and down-regulatory phases of gonadotropin-releasing hormone action.

Chronic treatment with agonist analogs of GnRH or long term continuous administration of GnRH results in down-regulation of pituitary LH secretion. We investigated the changes in the LH subunits during the stimulatory and down-regulatory phases of GnRH action in rat pituitary cell monolayer culture. The rat pituitary cells in culture, pretreated with medium alone or GnRH agonist for 48 h, were incubated with graded doses of GnRH for 4 h, and LH, LH alpha, and LH beta concentrations in the media and cell pellets were measured by specific and sensitive RIAs. Cells pretreated with medium alone responded to GnRH with a dose-dependent increase in LH, LH alpha, and LH beta immunoreactivity in the medium. However, rat LH, LH alpha, and LH beta concentrations in the cell pellets showed a dose-dependent decrease with GnRH treatment. Pretreatment with GnRH agonist led to a marked decrease in the LH response of cells to graded doses of GnRH. During this down-regulatory phase, the concentrations of LH beta in the medium remained undetectable even though LH alpha immunoreactivity remained persistently and disproportionately elevated. These data suggest that the alpha- and beta-subunits of rat LH are both coordinately and differentially regulated. During the stimulatory phase of GnRH action, both subunits rise concordantly, but during the down-regulatory phase the secretion of the two subunits becomes unbalanced. The changes in the beta-subunit closely parallel the changes in the concentrations of LH dimer, pointing to the key role of beta-subunit in regulation of LH secretion.

Animals↗
PubMedDate not supplied

Testosterone dose-dependency of sexual and nonsexual behaviors in the gonadotropin-releasing hormone antagonist-treated male rat.

The testosterone dose-dependency of several mating and nonmating behaviors was examined in the male rat, chemically castrated with a GnRH antagonist analog. Graded doses of testosterone enanthate (TE) were given to male rats to reinstate behaviors abolished by GnRH antagonist treatment. GnRH antagonist treatment alone markedly lowered serum LH, FSH and T concentrations and ventral prostate and testis weights. Open field behaviors were not significantly affected by GnRH antagonist treatment or castration. Scent-marking behavior was markedly suppressed by both castration and GnRH antagonist and restored by the lowest dose of TE (0.05 mg). All measures of male sexual behavior were impaired by GnRH antagonist treatment and castration and restored by the lowest dose of TE (0.05 mg). The doses of TE required to restore normal ventral prostate weights and testis weights were higher than those required to maintain scent marking and mating behaviors. No direct behavioral effects of the GnRH antagonist, other than those that can be explained by GnRH antagonist-induced suppression of testosterone were observed. The finding that sexual and nonsexual behaviors in the male rat have different testosterone requirements from those maintaining spermatogenesis and fertility may have significant implications for contraception.

Animals↗