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Biomedical subjects

F C Wu

Publications and source records attributed to F C Wu.

At least 55 records · Page 3Linked to original sources
PubMed1996

Male contraception.

With the powerful tools of molecular investigation, the last decade has witnessed the most remarkable scientific advance in our history, yet no new leads for male contraception have been forthcoming. All the likely methods of male contraception discussed above were derived from relatively 'old' physiological principles or serendipitous observations. The increasing gap between fundamental research (in the control of mammalian spermatogenesis) and the lack of clinical application are a testament to the low public funding priority afforded to male reproduction and the unwillingness of the pharmaceutical industry to invest in male reproductive research and development. Yet amidst such an unfavourable setting and with very limited support, it is heartening to note that the prospects of introducing a new systemic method for male contraception into the market by the end of this millenium has been greatly enhanced. Thus the results of recent studies have confirmed the contraceptive efficacy of sex steroid-induced oligozoospermia and unexpectedly revealed an ethnically distinct pattern of susceptibility to the hormonal suppression of spermatogenesis. Thus, Asian men are more responsive than are caucasian, and long-acting testosterone esters now being tested in that most densely populated part of the world may well hasten the large-scale application of this method. This is probably the most effective way to correct the misconceptions that men are unwilling or disinterested in sharing in family planning options with their partners. Together with the increased acceptance of novel non-surgical and reversible methods of vas deferens occlusion and the availability of improved non-latex condoms, the currently unfulfilled contraceptive needs of millions of men can be increasingly met in future years. The consequent increase in overall contraceptive prevalence could well make the telling difference between demographic catastrophe and maintaining good quality existence. Politicians, scientists and industrialists need to wake up to their responsibilities and the opportunities offered by this untapped resource and market potential.

Contraception↗
PubMed1996

Differentiation of normal male prepuberty and hypogonadotrophic hypogonadism using an ultrasensitive luteinizing hormone assay.

BACKGROUND AND OBJECTIVE: To assess how the Delfia time-resolved immunofluorometric assay can most conveniently and economically be used to differentiate normal prepuberty from complete idiopathic hypogonadotrophic hypogonadism (IHH, Kallmann's syndrome). SUBJECTS: 42 prepubertal boys aged 8.06-14.1 years and 11 adult male patients with IHH. DESIGN AND MEASUREMENTS: Blood samples were withdrawn at 20-min intervals for 8 h from 23.00 to 07.00. Samples from the 6 h commencing 1 h after sleep onset were analysed for LH by Delfia. RESULTS: Mean LH over this 6-hour period discriminated between IHH and normal prepuberty after the age of 12.5 years (no IHH subject > 0.31 U/l, no prepubertal subject < 0.33 U/l). The maximum hourly mean LH value for each subject gave a greater degree of mutual exclusivity (no IHH subject > 0.45 U/l, no prepubertal subject < 0.50 U/l). CONCLUSION: Kallmann's syndrome patients can be distinguished from prepubertal boys aged 12.5 years or over by blood sampling every 20 min for 6 h, commencing 1 h after sleep onset. The pooling of these samples into six 1-hour samples and subsequent Delfia assay will yield six 1-hour mean LH concentrations for each subject. The highest of these six concentrations will give a value with mutual exclusivity between the two groups.

Adolescent↗
PubMed1996

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate.

Hormonal suppression of spermatogenesis is currently being investigated as a method of reversible male contraception. However, administration of exogenous testosterone (T) induces azoospermia in only 40-70% of Caucasian men, whereas the remainder suppresses to severe oligozoospermia (< 5 x 10(5)/mL). The reason(s) for the heterogeneity in the spermatogenic response is not clear. We have prospectively investigated the possibilities that higher plasma concentrations of T and/or differences in the extent and rate of gonadotropin suppression could maintain a low level of spermatogenesis in subjects taking part in a clinical efficacy trial of hormonal male contraception. Thirty-three healthy adult men, aged 21-41 yr, were given 200 mg T enanthate (TE), im, weekly for up to 18 months. Azoospermia was achieved in 18 men (55%) after 20 weeks of treatment, at which time the remaining 15 (45%) stabilized at a mean sperm density of 2.0 +/- 0.8 (+/- SD) x 10(6)/mL. These 15 subjects remained oligozoospermic for the rest of the efficacy study. To compare the pharmacokinetics and pharmacodynamics of TE between the azoospermic and oligozoospermic responders, plasma samples were obtained immediately before and 1, 2, 4, and 7 days after the 1st and 16th TE injections. Further samples were taken after 2, 4, 8, and 12 weeks of treatment. Plasma concentrations of total, free, and non-sex hormone-binding globulin (non-SHBG)-bound T, estradiol, LH, and FSH were measured. Compared to baseline, preinjection levels of total T increased 2.5-fold, reaching a steady state around 12 weeks of treatment. Peak concentrations of total T increased by 5-fold, but free and non-SHBG-bound T levels were increased by 10-fold after 16 weeks. The plasma levels of estradiol showed similar changes as T. However, neither T (bound or free) nor estradiol was significantly different between azoospermic and oligozoospermic responders. Plasma SHBG was reduced to a similar degree in both groups of men after 16 weeks of TE treatment. Plasma concentrations of both LH and FSH decreased rapidly after the first TE injection; a significant decline in LH was detectable after 24 h. Mean levels of both gonadotropins decreased to less than 0.5 U/L by the end of 4 weeks and to below the limit of sensitivity of the assays (0.05 IU/L) by 12 weeks. There were no significant differences in plasma concentrations of LH or FSH or in the rates of suppression between azoospermic and oligozoospermic responders. We conclude that the polymorphism of spermatogenic suppression in response to exogenous T is unlikely to be due to differences in the pharmacokinetics or pharmacodynamics of TE or in the sensitivity of the hypothalamo-pituitary-testicular axis to sex steroid inhibition. Measurements of total plasma T considerably underestimate the increase in bioavailable T during the weekly TE regimen.

Adult↗
PubMed1996

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5 alpha-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone.

The administration of exogenous testosterone (T) to eugonadal men causes suppression of gonadotropin secretion and thus of spermatogenesis. This is currently being investigated as a possible method of hormonal male contraceptive, but complete suppression of spermatogenesis to azoospermia is induced in only 50-70% of Caucasian men; the remainder maintain a low rate of spermatogenesis. The basis for this polymorphism in response is unclear. The enzyme 5 alpha-reductase (5 alpha R) converts T to dihydrotestosterone (DHT) and is important in determining the magnitude of the androgen stimulus in some tissues. We investigated whether the maintenance of spermatogenesis in men remaining oligozoospermic while receiving suppressive doses of T is associated with evidence of increased 5 alpha R activity. Thirty-three normal men were given 200 mg T enanthate (TE), im, weekly in a clinical trial of hormonal male contraception. The MCR of T (MCRT) and the conversion ratio of T to DHT (CRT-DHT) were measured by infusion of [3H]T, plasma levels of DHT and androstanediol glucuronide (AdiolG) were measured by RIA, and 24-h urinary steroid metabolites were measured by capillary column gas chromatography. Sperm density decreased in all men; 18 achieved azoospermia by 20 weeks of treatment, and the remainder had a mean sperm density of 2.0 +/- 0.8 x 10(5)/mL at that time. This treatment caused increases in plasma T levels and MCRT, but with no differences between azoospermic and oligozoospermic responders. There were no differences in CRT-DHT plasma DHT, or AdiolG before treatment, but after 16 weeks, CRT-DHT had increased in the oligozoospermic responders, but not in the azoospermic responders. TE treatment increased plasma DHT and AdiolG levels in both groups, but the increases in both 5 alpha R metabolites were significantly greater in the oligozoospermic responders. Urinary excretion of etiocholanolone and androsterone was increased after 16 weeks of TE treatment, but did not differ between the two groups, andetiocholanolone/androsterone ratios did not differ greatly from unity. There was no change in urinary excretion of tetrahydrocortisol, allo-tetrahydrocortisol, or cortisone after 16 weeks of TE treatment in either group. These results suggest that after TE administration there is a selective increase in 5 alpha R activity in those men who remain oligozoospermic, but not in those becoming azoospermic. This difference in the androgenic milieu may underlie the incomplete suppression in the oligozoospermic responders, in whom a low rate of spermatogenesis is maintained despite the apparent absence of gonadotropins.

Adult↗
PubMed1996

Ontogeny of pulsatile gonadotropin releasing hormone secretion from midchildhood, through puberty, to adulthood in the human male: a study using deconvolution analysis and an ultrasensitive immunofluorometric assay.

The ontogeny of gonadotropin releasing hormone pulse generator activity underlying pubertal development in the human male is incompletely defined because of the limitations of assay sensitivity in measurements and the inaccuracies attendant upon the analyses of pulsatile secretion of circulating gonadotropins. Using an ultrasensitive immunofluorometric assay (DELFIA) to measure plasma LH and deconvolution analysis to depict LH secretory characteristics, we compared nocturnal (2000-0800 h) pulsatile LH secretion cross-sectionally in 16 boys in midchildhood (mean +/- SD age 6.6 +/- 0.3 yr), 8 prepubertal boys (12.0 +/- 0.3 yr), 8 early pubertal boys (14.3 +/- 0.4 yr), and in 8 young fertile adult men (32.6 +/- 1.6 yr) as an indirect in vivo assessment of hypothalamic GnRH pulse generator activity over the entire span of pubertal development in the human male. We confirmed that sleep-entrained GnRH/LH burst secretory activity was present in midchildhood. The first increase in sleep-entrained GnRH/LH secretion occurred some 2 yr before the clinical onset of puberty. From midchildhood to sexual maturity, LH production rate increased 39-fold. However, GnRH/LH pulse frequency showed only a relatively small (1.8-fold) increment from midchildhood to the clinical onset of puberty, with no subsequent changes to continuing development towards adulthood. Thus 91.7% of the increment in LH plasma concentration from childhood to sexual maturity could be accounted for by an amplification of a pre-existing ultradian rhythm of secretion with a steadily and markedly increasing mass of LH secreted per burst. The duration of secretory burst and apparent half-life of plasma LH disappearance remained constant from midchildhood, through puberty, to adulthood. The nyctohemeral rhythm-and sleep-associated LH/GnRH secretion was eventually lost in young adulthood. We conclude that the onset of puberty in man is heralded by the reawakening of a partially quiescent GnRH pulse generator. This predominantly involves an amplification of a pre-existing pattern of hypothalamic GnRH secretion leading to a major augmentation of the total quantity of LH molecules released per burst. The almost two-fold increment in GnRH pulse frequency contributed synergistically to the pubertal process, before the clinical onset of puberty, possibly by enhancing gonadotropic sensitivity to increase the mass of LH produced per burst. The relative constancy of GnRH pulse frequency in the gonad-intact hypothalamic-pituitary-testicular axis from pubertal onset to adulthood implies that testicular steroidal feedback plays a role in restraining the burst frequency of the GnRH pulse generator during pubertal development and adulthood.

Adolescent↗
PubMed1996

Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility.

OBJECTIVE: To evaluate the secondary impact of a prototype androgen contraceptive regimen on physical, metabolic and behavioral variables. DESIGN: Prospective, open, noncomparative contraceptive efficacy study. SETTING: International multicenter study comprising 10 centers in seven countries. SUBJECTS: Two hundred seventy-one healthy men, age 31.8 +/- 5.4 years (mean +/- SD), range 21 to 45 years. INTERVENTIONS: Weekly IM injections of 200 mg T enanthate. MAIN OUTCOME MEASURES: Adverse effects and discontinuations; biochemical and hematologic changes and interpopulation differences. RESULTS: Chinese subjects were shorter and lighter and their baseline hemoglobin, plasma lipid, and liver enzyme levels were lower than in non-Chinese subjects. The most common side effects were painful injections, acne, fatigue, and weight gain. Gynecomastia and prostate problems were detected in 24 and 9 men, respectively, though no men stopped injections for such reasons. Testosterone enanthate increased body weight, hemoglobin, and urea but decreased testicular volume and creatinine. Plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol were unchanged; high-density lipoprotein cholesterol decreased by 14% to 18% in non-Chinese but was unchanged in Chinese men. Liver transaminases were increased by 36% to 51% in Chinese but were unchanged in non-Chinese subjects. These T enanthate-induced effects were reversible within 6 months of stopping injections and were not related to the duration of T exposure. CONCLUSIONS: Testosterone enanthate administration in a contraceptive trial produced significant but reversible effects on skin, muscle, liver, lipid metabolism, and hemopoietic functions that varied between population groups. These effects reflect the relatively high peak levels and fluctuations of plasma T produced by the weekly T enanthate regimen rather than an inherent feature of hormonal male contraception. The results highlight the need for long-acting preparations of T with more stable delivery kinetics.

Adult↗
PubMed1996

In vitro translation of the full-length RNA transcript of figwort mosaic virus (Caulimovirus).

The circular DNA genome of FMV consists of seven tandemly arranged genes placed successively on a full-length RNA transcript that spans the entire circular viral genome. This transcript is a tentative mRNA for at least five of the six major conserved genes of this virus (genes I-V) that are positioned on this transcript. The sixth major gene (gene VI) is expressed as a separate monocistronic transcript. A long 5'-nontranslated leader (598 nucleotides), a small nonconserved gene (VII), and a short intergenic region (57 nucleotides) precede the five major conserved genes (I through V) on the full-length transcript. A reporter gene (CAT), as a separate cistron or fused in-frame, to viral cistrons in various downstream positions in cloned versions of the viral genome was used in a transcription vector to generate artificial full-length transcripts of FMV. When these mRNAs were translated in vitro (rabbit reticulocyte lysate system), the reporter gene was translated efficiently in all positions. Translation of internal native viral gene positioned on the full-length transcript of FMV was also determined (the gene VI product). These observations suggest that the full-length FMV transcript functions as a polycistronic mRNA in plants. Results are best explained on the basis of translational coupling/relay race model.

Animals↗
PubMed1995

Effect of testosterone enanthate on serum lipoproteins in man.

Sixty-three normal Caucasian men were administered intramuscular testosterone enanthate (TE) 200 mg i.m. weekly for 12 months as part of a male contraceptive trial. This dose of TE caused a 2.5-fold increase in trough serum testosterone concentrations. High density lipoprotein cholesterol (HDL-C) was significantly depressed from pretreatment concentration of 1.19 +/- 0.04 nmol/l to 1.03 +/- 0.04 mmol/l after 12 weeks of treatment, and remained suppressed for the duration of treatment (p < 0.001). There were no changes in serum concentration of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) or triglycerides (TG) during treatment, but the concentrations of TC and LDL-C were depressed at three months post-treatment. There was a sustained elevation in LDL-C:HDL-C ratio during TE treatment (p < 0.005), from 3.41 +/- 0.15 pretreatment to 3.88 +/- 0.19 after 12 weeks of TE treatment. Sex hormone binding globulin (SHBG), but not testosterone (T) or estradiol (E2), was significantly associated with HDL-C (r = 0.83, p = 0.001). Lipoprotein (a) (Lp(a)) was measured in a subgroup of 33 men: serum concentration fell from 187 +/- 45 mg/l pretreatment to 140 +/- 35 mg/l after 16 weeks of TE treatment (p < 0.01).

Adult↗
PubMed1995

A double blind, placebo controlled study of the effects of low dose testosterone undecanoate on the growth of small for age, prepubertal boys.

OBJECTIVE: To assess whether very low doses of testosterone can accelerate growth without an undue advance in bone age in prepubertal boys with constitutional delay of growth. SUBJECTS: 23 prepubertal boys aged 11-14 years with height at or below the third centile for chronological age. DESIGN: Randomised, double blind trial comparing oral testosterone undecanoate 20 mg once daily versus placebo for six months. The 18 months' observation period of each subject comprised a six month pretreatment period, followed by a six month treatment (testosterone undecanoate or placebo) period, and a six month period after termination of treatment. OUTCOME MEASURES: At intervals of six months standing and sitting height were measured. Bone age, pubertal stage, weight, and lean body mass were also determined. Growth hormone, luteinising hormone, and follicle stimulating hormone secretion and testosterone concentration were measured before, after, and six months after treatment. RESULTS: Boys taking testosterone undecanoate (n = 11) showed a significantly greater height velocity (mean (SEM) 5.84 (0.53) cm/year) and sitting height velocity (3.54 (0.57) cm/year) during treatment than the placebo treated boys (n = 12, height velocity = 3.38 (0.22) cm/year, sitting height velocity = 1.58 (0.19) cm/year. There were no significant differences between the groups regarding changes in growth hormone, gonadotrophins, testosterone, or dihydrotestosterone concentrations. Bone age was not advanced significantly more rapidly in either group. CONCLUSIONS: There is accelerated gain in height during six months of treatment with low dose testosterone undecanoate, without a significantly greater rise in bone age compared with controls. Testosterone undecanoate is a safe, well tolerated, and effective treatment in the management of constitutional delay of growth.

Adolescent↗
PubMed1995

Haemostatic effects of supraphysiological levels of testosterone in normal men.

The effects of exogenous testosterone on the haemostatic system were studied in a group of 32 healthy men undergoing a clinical trial of hormonal male contraception. The men received 200 mg testosterone oenanthate (TE) weekly i.m., and plasma samples were taken pretreatment, at defined time points up to 52 weeks of treatment, and 4 and 8 weeks after discontinuing TE. This dose of TE caused a 2-fold increase in trough plasma testosterone levels. TE caused a fall in plasma fibrinogen concentration after 16 weeks of treatment. This was sustained for the duration of TE treatment and recovered to pretreatment levels during the recovery phase. There was also a sustained fall in the level of C4b binding protein which showed a rebound to levels above pretreatment during recovery. Levels of antithrombin III and prothrombin fragment F1.2 rose initially during TE treatment, and levels of protein C, protein S (free) and plasminogen activator inhibitor fell, but the concentrations of these factors all returned to pretreatment levels during continued treatment. There was no change in the plasma concentrations of beta-thromboglobulin, tissue plasminogen activator, protein S (total), or D-dimer. There was a sustained increase in haemoglobin concentration and haematocrit, without any change in platelet count. The observed changes were consistent with mild activation of the haemostatic system during initial treatment with testosterone. After several months the raised activation markers had returned to pretreatment levels indicating that a new equilibrium had been established which did not appear to be prothrombotic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hypothalamic hamartoma with skeletal malformations, gelastic epilepsy and precocious puberty.

A child is described who has skeletal malformations, gelastic epilepsy, precocious puberty and a hypothalamic hamartoma. The skeletal abnormalities were detected at birth, she developed gelastic epilepsy at the age of 3 years 5 months and precocious puberty at 3 years 8 months. A hypothalamic hamartoma was found on MRI. The precocious puberty has been successfully medically managed, though her seizures are difficult to control. The combination of all four features has not been described previously.

Bone and Bones↗
PubMed1993

A modified technique of micro-arteriography utilizing dental X-ray equipment.

We report on the use of dental x-ray equipment for micro-arteriography in 18 rat arterial anastomoses. Our experience has shown that an exposure of 70 kV, at 7mA, for 0.17 seconds, gives excellent results. This is an easy and useful technique for evaluating the patency and stenosis of microvascular anastomoses.

Angiography↗
PubMed1993

Melatonin potentiates testosterone-induced suppression of luteinizing hormone secretion in normal men.

A total of 12 healthy adult men were recruited to investigate the effect of exogenous melatonin on the sensitivity of the hypothalamo-pituitary axis to sex steroid negative feedback. The experiment consisted of a double-blind, randomized cross-over trial during which all subjects received 100 mg oral melatonin or placebo at 1600 h for 14 days. Midway through each of the two treatments (day 8), 100 mg testosterone propionate i.m. (TP) was given at 0900 h. Blood samples for the measurement of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and melatonin were taken at 0900 h on days 1, 3, 5, and daily from days 8-14. An additional blood sample was taken 8 h after the administration of testosterone. The interval between the melatonin and placebo treatment periods was 2 months. The oral administration of melatonin caused a pharmacological increase in the blood plasma concentration of melatonin which was maximum at 2 h and still above normal at 24 h. The daily treatment thus resulted in persistently high circulating levels of melatonin for 14 days. This treatment had no significant effect on the secretion of LH, FSH, prolactin or testosterone based on the first week of each study (melatonin compared with placebo). The injection of TP caused a rapid 3 to 4-fold increase in the plasma concentrations of testosterone which was at a maximum at 8 h and had returned to baseline within 4 days, with a similar pattern in both the melatonin and placebo periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Homologous intra-uterine insemination has no advantage over timed natural intercourse when used in combination with ovulation induction for the treatment of unexplained infertility.

The objective was to evaluate the role of homologous intrauterine insemination compared with timed natural intercourse, both combined with ovulation induction, in the management of unexplained infertility. A total of 48 couples presenting at a large teaching hospital infertility clinic with unexplained infertility of at least 3 years duration comprised the main study group, and 36 couples with identical entry criteria but under the care of another clinician made up a parallel control group. A randomized design of treatment cycles with within-group and between-group controls was used. Couples in the main study group were treated with either homologous intra-uterine insemination or timed natural intercourse in gonadotrophin-releasing hormone analogue down-regulated cycles, in which ovulation was induced with human menopausal gonadotrophin and human chorionic gonadotrophin. Alternate cycles were monitored to enable optimum timing of natural intercourse provided within-group controls. Couples in the control group underwent timed homologous intravaginal artificial insemination. Cycle fecundity and pregnancy outcome in treated and control groups were monitored. Cycle fecundity of 0.11 in 85 ovulation-induced cycles was significantly higher than 0.02 in 62 within-group and 0.01 in 103 between-group control cycles. There was no difference in conception rates between homologous intra-uterine insemination and timed natural intercourse cycles with ovulation induction. Of the 11 established pregnancies in the ovulation induced group, nine delivered healthy babies (five singleton, three twin, one triplet) and two were ectopic. Results confirmed the value of active management for couples with long-standing unexplained infertility but failed to demonstrate any advantage of homologous intra-uterine insemination over ovulation induction alone.

Adult↗
PubMed1993

The putative zinc finger of a caulimovirus is essential for infectivity but does not influence gene expression.

Plant pararetroviruses, such as caulimoviruses, and animal retroviruses have in common the presence of a highly conserved arrangement of cysteines and a histidine in the precursor of the capsid protein. The composition of these amino acids resembles a zinc finger element, a structure that is common to a class of eukaryotic proteins that regulate gene expression. The role of the putative zinc finger in the life-cycle of caulimoviruses was investigated by introducing specific mutations in the coat protein coding region of a cloned and infectious form of figwort mosaic virus, a caulimovirus. This mutated viral genome, which no longer encoded the conserved cysteine and histidine residues, was not infectious in plants. Transient expression assays in protoplasts showed that expression of a reporter gene inserted at different places in the genome was not detectably influenced by the coat protein or its putative zinc finger. It appears that the zinc finger-like element of caulimoviruses is not involved in the regulation of gene expression. These observations support a model which predicts a function of the zinc finger in specific recognition and packaging of viral RNA into virions prior to reverse transcription.

Amino Acid Sequence↗
PubMed1993

Prostate-specific antigen and prostate gland size in men receiving exogenous testosterone for male contraception.

Steroid regimens containing androgens are being evaluated currently as hormonal contraceptives for men. The possible non-reproductive effects of such treatment were assessed during an efficacy trial using a prototype regime of 200 mg testosterone enanthate i.m. weekly. Prostatic function and size were monitored by regular rectal examination, blood levels of prostate-specific androgen (PSA) were measured in 30 men and prostatic size was measured by trans-rectal ultrasound imaging in a representative subgroup of five subjects for 12 months and for a further 6 months after discontinuation. Despite the sustained rise in serum levels of testosterone, oestradiol and dihydrotestosterone during treatment, there was no detectable increase in prostatic size on rectal examination or any significant change in blood concentrations of PSA. A small but significant increase (14.3 +/- 2.0%) in maximal prostate transverse area was observed in four men while the remaining one showed no change. Our preliminary data demonstrate the feasibility and importance of monitoring prostatic function in the development of androgen-containing male hormonal contraceptives.

Adult↗
PubMed1993

Early morning plasma testosterone is an accurate predictor of imminent pubertal development in prepubertal boys.

In the management of constitutional delayed growth and/or puberty, there is a need for simple tests which can assess the overall developmental maturity of the hypothalamic-pituitary-testicular axis in clinically prepubertal patients. This would enable the physician to predict the likelihood or otherwise of an individual entering puberty spontaneously within subsequent months. Based on our previous physiological data on the sequential pattern of peripubertal pituitary-testicular activation by hypothalamic GnRH, we hypothesized that the nocturnal secretion of testosterone, in response to sleep-entrained LH secretion, may provide a basis for an in vivo bioassay of neuroendocrine sexual maturity. Overnight testosterone secretion by the testis in clinically prepubertal boys was assessed with respect to their subsequent clinical progress, the target being the attainment of testicular volumes of greater than or equal to 4 mL (a clinical landmark when puberty has assuredly begun and virilization will soon follow). Forty-five prepubertal (Tanner stage G1PH1 testicular volume < or = 2 mL) boys aged 10.0-15.3 yr (mean +/- SEM 11.8 +/- 0.2) with short stature had paired plasma T concentration measured at 2000 h and 0800 h the following morning. After the initial assessment, all patients were reviewed clinically at 3-month intervals for a minimum of 21 months (mean 26.0 +/- 1.1, range 21-50 months). During this period, 38 (84.4%) patients received treatment in the form of sc human GH 2-4 IU daily or oxandrolone 2.5 mg daily by mouth to improve short-term growth although this did not have any significant effect on the subsequent timing of pubertal onset. The patients were divided according to whether 1) there was a demonstrable increase in plasma T between 2000 and 0800 h and 2) morning plasma T concentration was less than or greater than or equal to 0.7 nmol/L at their initial assessment. In those with a significant overnight T increment, 58% and 89% achieved testicular volume of greater than or equal to 4 mL after 12 and 21 months, respectively. In contrast, only 12% and 56% of patients who had not shown a T increase went into puberty by these times. In patients who had morning plasma testosterone concentrations greater than or equal to 0.7 nmol/L, 77% entered puberty within 12 months and 100% within 15 months. However, in those with a morning testosterone of less than 0.7 nmol/L, only 12.5% and 25% entered puberty within 12 and 15 months, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗