Non-sex Hormone Research Articles

A-053 Poor Clinical Utility of Free and Bioavailable Testosterone is Underscored by Overutilization

Abstract Background Symptomatic androgen deficiency has an estimate prevalence of 2%–12% in males over 40 years of age and is associated with several comorbidities such as hypertension, obesity, dyslipidemia, metabolic syndrome, diabetes, and COPD. Diagnosis relies heavily on the measurement of testosterone concentrations. While total testosterone (tT) is often sufficient to diagnose deficiency, free testosterone (fT) or bioavailable testosterone (baT; non-sex hormone binding globulin (SHBG)-bound) may be helpful in assessing patients with suspected hormone binding abnormalities. Consensus guidelines recommend relying on tT measurement and only using fT or baT testing when indicated. Despite these recommendations, requests for measured fT and baT account for a large percentage of testosterone orders in our institution. Here we examined the utilization of testosterone orders, assessed the clinical utility of measured fT and baT relative to tT alone, and devised a reflex algorithm to optimize fT and baT utilization. Methods Testosterone data was collected over a 12 month period, September 2020–August 2021. Only data from adult males with established reference intervals was included in the final cohort; ≥20 and 20–69 years of age for fT and baT, respectively. Logistic regression was used to determine the probability of low fT and baT based on tT concentration. An algorithm based on initial tT concentration was established to reflex to fT/baT when most likely to provide additional benefit. Results Of 9754 testosterone tests performed on male patients during the study period, 4514 (46%) included a measured fT and/or baT. After excluding data without established reference intervals, the final cohort consisted of 1851 fT and 2514 baT measurements. Overall concordance with tT was 70.0% and 74.8% for fT and baT, respectively. However, only 0.2% (3/1479) were found to have low fT and 8.4% (166/1988) low baT when tT was greater than the reference interval lower limit (i.e., normal or high). The probability of a patient having low fT or baT with normal tT peaked at 0.01 and 0.21, respectively, and was greatest at the tT reference interval lower limit (240 ng/dL). An algorithm was devised in which only samples with tT concentrations of 240–500 ng/dL would reflex to baT testing. In this cohort, 90% of discordant (low baT with normal tT) samples would have triggered the baT reflex while reducing the overall utilization of baT by 55%. Applying the same reflex algorithm would have also reflexed 100% of discordant fT samples. Conclusions Despite being performed with nearly half of all testosterone orders, baT, and especially fT, provided little additional clinical utility to tT alone. By determining the probability of a low baT or fT when Tt is above the reference interval lower limit, a reflex algorithm can be devised to help optimize baT and fT utilization. While this algorithmic approach has been proposed by others, the reflex values in our cohort differ significantly from previously published values suggesting that laboratories should determine limits based on their individual testosterone assays. The logistic regression method utilized here provides one such example laboratories can follow for undertaking such an analysis.

Honest signals and sexual conflict: Female lizards carry undesirable indicators of quality.

Sex differences in animal coloration often result from sex‐dependent regulatory mechanisms. Still, some species exhibit incomplete sexual dimorphism as females carry a rudimentary version of a costly male trait, leading to intralocus sexual conflict. The underlying physiology and condition dependence of these traits can inform why such conflicts remain unresolved. In eastern fence lizards (Sceloporus undulatus), blue iridophore badges are found in males and females, but melanin pigmentation underneath and surrounding badges is male‐exclusive. We track color saturation and area of badges across sexual maturity, and their relationship to individual quality (body condition and immunocompetence) and relevant hormones (testosterone and corticosterone). Saturation and testosterone were positively correlated in both sexes, but hormone and trait had little overlap between males and females. Saturation was correlated with body condition and immunocompetence in males but not in females. Co‐regulation by androgens may have released females from resource allocation costs of color saturation, even when in high condition. Badge area was independent of testosterone, but associated with low corticosterone in females, indicating that a nonsex hormone underlies incomplete sexual dimorphism. Given the evidence in this species for female reproductive costs associated with ornamentation, this sex‐nonspecific regulation of an honest signal may underlie intralocus sexual conflict.

Abstract 3488: Associations of circulating hormones with mammographic density in postmenopausal women referred to diagnostic breast biopsy

Abstract Introduction Elevated mammographic density (MD) is a strong and independent risk factor for breast cancer, though underlying mechanisms are unclear. Prior studies have suggested that increased cumulative exposure to sex-steroid hormones and growth factors may impact both MD and MD-related breast cancer risk; however, most studies have only evaluated individual hormones. In this study, we simultaneously explored the relationship between 29 circulating hormones and growth factors with MD among postmenopausal women undergoing diagnostic breast biopsy. Methods We used data from 89 postmenopausal women, aged 44-65, who had complete measurements of 29 serum hormones from a single pre-biopsy blood draw (i.e., sex-steroid hormones: 15 estrogen/estrogen metabolites, 7 progesterone/progesterone metabolites; and non-sex hormones: insulin-like growth factor I and binding proteins (IGFBPs) 2-7). Volumetric MD (% fibroglandular volume) was assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Sufficient dimension reduction methods were used to compute a composite marker score that accommodates correlations among hormones and their relationship to MD. Backward elimination was applied to select log-transformed hormones contributing to the score at α=0.05; multivariable linear regression was used to further examine associations between selected hormones and MD within a single model, adjusting for age and BMI. Results Pearson correlations between hormones were moderate-to-strong. Dimension reduction methods identified 6 hormones as associated with MD (p<0.05): estradiol, 2-hydroxyestradiol, 2-methoxyestrone, 16-ketoestradiol, IGFBP-2, and 17α-hydroxyprogesterone, in models that considered MD as either continuous or dichotomous (>median vs. ≤median); BMI was consistently identified as the most significant predictor of MD (P <0.0001). In a multivariable linear regression model that included these 6 hormones, in addition to age and BMI, higher levels of 2-methoxyestrone, IGFBP-2, and 17α-hydroxyprogesterone were significantly associated with increased MD, whereas higher levels of age and BMI were significantly associated with lower MD. Conclusions We identified 6 out of 29 correlated hormones that were significantly associated with MD among postmenopausal women. For several, the directions of their associations with MD were comparable to those observed in prior studies that have separately evaluated these hormones in relation to breast cancer risk. We plan to further explore how circulating hormones concurrently affect MD in premenopausal women, accounting for menstrual cycle phase. Incorporation of dimension reduction methods in studies of multiple correlated hormones can help uncover new etiologic insights into the role of hormones and growth factors in MD and breast carcinogenesis and inform strategies for prevention. Citation Format: Shaoqi Fan, Ruth M. Pfeiffer, Manila Hada, Roni T. Falk, Maeve Mullooly, Hannah Oh, Berta Geller, Pamela Vacek, Donald Weave, John Shepherd, Jeff Wang, Sally Herschorn, Louise A. Brinton, Xia Xu, Mark E. Sherman, Britton Trabert, Gretchen L. Gierach. Associations of circulating hormones with mammographic density in postmenopausal women referred to diagnostic breast biopsy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3488.

Pubertal Hormonal Changes and the Autonomic Nervous System: Potential Role in Pediatric Orthostatic Intolerance.

Puberty is initiated by hormonal changes in the adolescent body that trigger physical and behavioral changes to reach adult maturation. As these changes occur, some adolescents experience concerning pubertal symptoms that are associated with dysfunction of the autonomic nervous system (ANS). Vasovagal syncope (VVS) and Postural Orthostatic Tachycardia Syndrome (POTS) are common disorders of the ANS associated with puberty that are related to orthostatic intolerance and share similar symptoms. Compared to young males, young females have decreased orthostatic tolerance and a higher incidence of VVS and POTS. As puberty is linked to changes in specific sex and non-sex hormones, and hormonal therapy sometimes improves orthostatic symptoms in female VVS patients, it is possible that pubertal hormones play a role in the increased susceptibility of young females to autonomic dysfunction. The purpose of this paper is to review the key hormonal changes associated with female puberty, their effects on the ANS, and their potential role in predisposing some adolescent females to cardiovascular autonomic dysfunctions such as VVS and POTS. Increases in pubertal hormones such as estrogen, thyroid hormones, growth hormone, insulin, and insulin-like growth factor-1 promote vasodilatation and decrease blood volume. This may be exacerbated by higher levels of progesterone, which suppresses catecholamine secretion and sympathetic outflow. Abnormal heart rate increases in POTS patients may be exacerbated by pubertal increases in leptin, insulin, and thyroid hormones acting to increase sympathetic nervous system activity and/or catecholamine levels. Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. Further research is necessary to confirm the effects of female pubertal hormones on autonomic function, and their role in pubertal autonomic disorders such as VVS and POTS, in order to inform the treatment and management of these debilitating disorders.

Risk Factors for Endometrial Cancer among Post-menopausal Women in South Africa

Background: National Cancer Registry of South Africa reported the highest incidence of uterine cancer in Gauteng Proviance. Among uterine cancer patients reported in the Department of Radiation Oncology, Johannesburg Hospital, more than 85% are suffering in endometrial cancers. Here, in this study we tried to explore the relation between factors causing increased blood oestrogen levels, like, contraceptive pills, early menarche and delayed menopause (increases the length of menstruation), nulliparity and overweight by more than 25kg and endometrial cancer among black female population of Greater Johannesburg. In this present study, we also studied how non-sex hormone related factors like hypertension, diabetes, family history, obesity and smoking habits are affecting the occurrence of endometrial cancer in Greater Johannesburg females.Methods: This study is based on post-menopausal female black population of Johannesburg who were physically examined with the help of transvaginal sonar. Their oestrogen level in serum was checked. Their family history, menarche and menopause age, pregnancy and others were collected through questionnaires.Results: The mean age of menarche and menopause was found to be 13.80 and 53.80 years respectively. Hypertension, elevated serum oestradiol level, nulliparity, obesity and diabetes are significantly high among study group. Moreover our study suggests no such relation between smoking habit and endometrial cancer.Conclusion: Continued exposure of endometrium to oestrogen increases the chance of endometrial cancer. The length of menstruation time and nulliparity appeared as vital factors for endometrial cancer. Moreover, adipocytes secreting oestrogen and diabetes are also related to the onset of endometrial cancer among post-menopausal female population.

Novel insights into the puberty switch mechanisms of the sex bias in human asthma

Abstract The gender bias in human asthma prevalence changes with puberty, with males having a higher asthma incidence before puberty and females having higher rates after. The mechanisms involved in this switch are unknown. Our previous research showed that multiple hormonal systems are dysregulated in allergic disease. Because sex hormones interact with all endocrine system axes, we hypothesized that non-sex hormones and their downstream functions in allergic disease are driven by sex related changes in puberty. Measuring non-sex hormone protein levels from human serum samples by multiplex ELISAs, we found a striking sexual dimorphism in endocrine regulation. Pre-puberty asthmatic males had higher T3, T4, and GH levels compared to healthy controls, and pre-puberty asthmatic females had lower C-peptide and insulin levels. Interestingly, we saw the opposite pattern post-puberty. In a kinetic murine ovalbumin asthma model, adult male mice had higher C-peptide and insulin baseline levels, which were maintained during inflammation. Males also had higher GIP levels in the acute phase and higher PP, PYY, and resistin levels in the model’s late phase. Since hormones regulate tissue homeostasis, we examined the puberty switch in key epithelial remodeling markers in the inflamed mouse lung. Thbs2, Nes, Postn, Tnc, and Wnt5a expression was different relative to baseline in both sexes pre-puberty, but only females had altered expression of these markers post-puberty. Interestingly, though the Th2 immune response was higher in females post-puberty, there was no sexual dimorphism pre-puberty. These results implicate that sex hormones exert systemic level regulation determining the age and gender dependent progression of asthma pathogenesis.

Alteration of Sex and Non-Sex Hormones and Distribution Features of Blood ABO System Groups among the Women with Uterine Body Tumors

Objectives: The aim of the investigation was to study the hormonal status (sex hormones: estradiol (E2), progesterone (P), testosterone (T); non-sex gonadotropic hormones-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) of women with benign and malignant tumors of uterine body in the reproductive, menopause and postmenopause periods. Also the distribution features of the blood ABO system phenotype groups and their link to the development of uterine body tumors have been studied. Methods: The determination of hormones was made by the enzyme analysis method (ELAIZA), provided by the proper ELAIZA kits. For the study of blood ABO system antigens, internationally recognized immunoserology methods were used. Results: Investigations revealed the increased level of E2 and T on the background of the reduced P in the blood of the women with uterine tumors in the reproductive, menopause and post-menopause period. As for gonadotropic hormones, the decreased levels of LH and FSH have also been detected. From the ABO system phenotype groups A(II) group had the highest frequency between the women with malignant uterine tumor in the reproductive age. O (I) phenotype group was the most frequent in case of menopause and post-menopause women with uterine malignant tumors. Conclusions: Hormonal imbalance creates good conditions for the proliferation of uterine tissues and hence causes the development of benign and malignant uterine tumors. The imbalance of the sex steroid and gonadotropic hormones in the blood of post-menopause women indicates on the genotoxic mechanism of cancer development on the background of age-related changes. A(II) group had the highest frequency between the reproductive age women with uterine malignant tumor, while O (I) group was the most frequent in case of menopause and post-menopause patients.

Analytical and physiological factors affecting the interpretation of serum testosterone concentration in men

Most hospital laboratories estimate the concentration of total circulating testosterone using a non-extraction method on an automated multi-channel immunoassay analyser supplied by a small number of multi-national diagnostic companies. Although these platforms offer advantages of quick turnaround times, small volume sampling and random access analysis, proficiency testing schemes suggest the quality of results produced remains similar to that of the early manual radioimmunoassay. An estimate of the bioavailable, non-sex hormone binding globulin (SHBG) bound fraction of circulating testosterone, be that the free or the free plus albumin-bound, may be a better index of gonadal status than total testosterone alone, especially when a borderline hypogonadal level of total testosterone is found, and may avoid misclassification of hypogonadal or eugonadal men. Free or bioavailable testosterone may be calculated or measured. The free androgen index may not give a true reflection of androgen status in men. In the interpretation of serum testosterone concentrations with results >40 nmol/L, the possibility of exogenous administration or abuse needs to be considered. The marked diurnal rhythm in total testosterone should also be taken into account. There may be a diminution of testosterone secretion with advancing age, but the great majority of older men have a circulating total testosterone concentration well within the accepted reference intervals established for younger men. As testosterone concentration may fluctuate markedly both seasonally and from day to day, it may be judicious to measure levels on more than one occasion. Provided that estimates of serum testosterone are unequivocally eugonadal (12.5-40 nmol/L) or hypogonadal (<7.0 nmol/L), results produced by routine automated immunoassays will in all probability give a satisfactory assessment of androgen status in men.Routine biochemical assessment of gonadal function in men should include measurement of early morning luteinizing hormone, follicle stimulating hormone, prolactin and SHBG together with total testosterone, and if necessary some estimate of bioactive testosterone.

Once and twice a week transdermal estradiol delivery systems: clinical efficacy and plasma estrogen levels

We compared the clinical efficacy and circulating estrogen levels from two transdermal delivery systems, ‘drug-in-adhesive’ type, in 20 healthy postmenopausal women. Both patches, developed by Beta Pharmaceutical Laboratories in Argentina, deliver estradiol at a rate of 50 fig/day; the replacement frequency of system A (TrialSat®) was twice a week and for system B (TrialSat LA®) once a week. The women were treated for 180 days, in a continuous regimen, with additional oral medroxyprogesterone acetate 5 mg/ day for 14 days of each cycle. Blood samples were taken at the end of the wearing period: the 3rd day for Group A and the 7th day for Group B, to determine levels of estradiol, estrone, non-sex hormone binding globulin (SHBG)-bound estradiol and SHBG. Both treatments had similar clinical efficacy and were well tolerated. Plasma estradiol levels were higher in Group A throughout the study, probably owing to the different sampling times. SHBG and non-SHBG-bound estradiol were unchanged in both groups.As there was a similar performance of both delivery systems, the 7-day patch may be preferable, and produce greater compliance.

Hormonal responses to training and its tapering off in competitive swimmers: relationships with performance.

During a winter training season, the effects of 12 weeks of intense training and 4 weeks of tapering off (taper) on plasma hormone concentrations and competition performance were investigated in a group of highly trained swimmers (n = 8). Blood samples were collected and the swimmers performed their speciality in competition at weeks 10 (mid-season), 22 (pre-taper) and 26 (post-taper). No statistically significant changes were observed in the concentrations of total testosterone (TT), non-sex hormone binding globulin-bound-testosterone (NSBT), cortisol (C), luteinising hormone, thyroid stimulating hormone, triiodothyronine, thyroxine plasma catecholamines, creatine kinase and ammonia during training and taper. Mid-season NSBT: C ratio and the amount of training were statistically related (r = 0.82, P < 0.05). Competition performance slightly declined during intense training [0.52 (SD 2.51)%, NS] and improved during taper [2.32 (SD 1.69)%, P < 0.01]. Changes in performance during training and taper correlated with changes in ratios TT: C (r = 0.86, P < 0.01 and r = 0.81, P < 0.05, respectively) and NSBT: C (r = 0.77, P < 0.05 and r = 0.76, P < 0.05, respectively). In summary, these results showed that the monitored plasma hormones and metabolic indices were unaltered by 12 weeks of intense training and 4 weeks of taper. The TT: C and NSBT: C ratios, however, appeared to be effective markers of the swimmers' performance capacities throughout the training season.

Oral testosterone undecanoate in the management of delayed puberty in boys: pharmacokinetics and effects on sexual maturation and growth.

Therapeutic induction of puberty using oral testosterone (T) undecanoate (TU) 40 mg daily was performed in 4 pubertal boys aged 12.7-17.1 yr with constitutional delayed puberty and/or short stature. Single-dose pharmacokinetics study was performed on matched plasma and saliva samples obtained half-hourly for 10 h after the first dose and then repeated 3 and 6 months later. Treatment was continued for 15-21 months. Peak plasma total T concentration was achieved at 255 +/- 51 (SEM) min after the first 40 mg dose of TU, 300 +/- 76 min at 3 months, and 293 +/- 103 min at 6 months, the levels remaining elevated above baseline for at least 8 h after a single oral dose. Total T levels were initially high (mean 13.0 +/- 2.5; peak 38.7 +/- 4.2 nmol/L) but dropped significantly at 3 months (mean 8.3 +/- 1.8; peak 23.6 +/- 5.6 nmol/L) and at 6 months (mean 9.2 +/- 1.6; peak 24.8 +/- 3.5 nmol/L) paralleled by a dramatic fall in sex hormone binding globulin (73.9 +/- 18.0 to 35.1 +/- 9.7 at 3 month and 29.2 +/- 6.0 nmol/L at 6 month). Mean concentrations of unbound and free T (non-sex hormone binding globulin-bound T, free T, and salivary T) were below the normal adult range and remained unchanged over the same period. Plasma dihydrotestosterone concentrations were elevated after the first dose (mean 5.4 +/- 1.3; peak 11.0 +/- 2.5 nmol/L), the extent of this rise being less after 6 months (mean 4.1 +/- 0.8; peak 7.1 +/- 1.1 nmol/L) as was the case with mean estradiol (51.5 +/- 8.9 to 38.1 +/- 3.7 pmol/L). Signs of virilization progressed to Tanner stage G3 PH2-3 with testicular volumes increasing to 3-4 mL at 12 months, and G4 PH4-5 with further testicular growth to 6-10 mL at 24 months. Height velocity rose from 3.2 +/- 0.3 cm/yr (pretreatment) to 7.2 +/- 1.0 cm/yr in the first year and was maintained at 7.3 +/- 0.4 cm/yr despite cessation of therapy during the second year. Bone age advanced by 1.1 +/- 0.1 yr at 12 months and a further 0.8 +/- 0.3 yr at 24 months. Predicted adult height remained unchanged. No side effects were observed. Our preliminary data suggest that oral TU is a well accepted, effective, and safe treatment for the initiation of male puberty without disproportionate skeletal maturation. Continued pubertal advance was evident after cessation of treatment in all patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of non-sex hormones on neuronal excitability, seizures, and the electroencephalogram.

Several of the non-sex hormones have been found to be useful in the treatment of seizures. These hormones have an effect on seizures, and seizures have an effect on these hormones. Adrenocorticotropic hormone (ACTH) and corticosteroid drugs have been found to be useful in the treatment of infantile spasms and other seizure disorders. Unfortunately, there is no clear consensus regarding superiority of ACTH versus prednisone in regard to efficacy and long-term benefits, dosage, or duration of treatment. There is also considerable debate regarding reasons why ACTH and prednisone are useful in infantile spasms, their mechanism of action, and their long-term effects on brain development. Thyrotropin-releasing hormone also has been used in the treatment of infantile spasms and other seizure types in children, with modest success. As with ACTH and prednisone, the mechanisms of action remain unclear.

Sex hormones in postmenopausal women with primary biliary cirrhosis

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p <0.05) elevated serum concentrations of estrone and androstenedione and significantly (p <0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5α-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p> 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p < 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p < 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction. (HEPATOLOGY 1991;13:865–869.)

Sex hormones in postmenopausal women with primary biliary cirrhosis

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome.

We have investigated the hypothesis that hyperinsulinemia may cause the polycystic ovary syndrome (PCO) by directly stimulating gonadal steroidogenesis and/or gonadotropin secretion. 10 insulin-resistant women with PCO and 5 age- and weight-matched ovulatory normal women had pulsatile gonadotropin release, gonadotrope sensitivity to gonadotropin-releasing hormone, and sex hormone levels studied on two consecutive study days, basally and during the infusion of insulin (mean +/- SEM steady state insulin levels, 1,254 +/- 63 microU/ml PCO vs. 907 +/- 92 microU/ml normal, P less than or equal to 0.01). Insulin acutely increased mean delta (6 h minus prestudy) levels of androstenedione (A) (P less than or equal to 0.001) and estradiol (E2) (P less than or equal to 0.05) and decreased mean plasma pool (0-6 h) levels of testosterone (T) (P less than 0.05), nonsex hormone binding globulin-bound T (P less than 0.05), and dihydrotestosterone (P less than or equal to 0.01) in the PCO women. Insulin also decreased mean plasma 6 h A to estrone (E1) ratios and increased 6 h E1 levels (both P less than or equal to 0.05) in the PCO women. There were significant sequence effects (insulin + day) in the PCO women on T/E2 ratios, indicating a carryover action of insulin. Insulin had no effects on gonadotropin release in the PCO women. In the normal women, the only significant change was an insulin or study day effect that increased mean 6 h E2 levels (P less than or equal to 0.01). There were significant spontaneous decreases in mean luteinizing hormone (p less than 0.05) and follicle-stimulating hormone levels (p less than or equal to 0.01) in the PCO but not the normal women on the second day of study. This study indicates that insulin can directly alter peripheral sex hormone levels independent of changes in gonadotropin release in insulin-resistent PCO women. Insulin decreased the levels of potent androgens in PCO women and did not increase androgen levels in normal women, arguing against a simple, direct causal relationship between hyperinsulinemia and hyperandrogenism in PCO.

Androgen therapy of hypogonadal men with transscrotal testosterone systems

The need for improved controlled delivery of testosterone to hypogonadal men stimulated the development of a self-adherent transscrotal testosterone system to provide programmed testosterone delivery through the uniquely permeable scrotal skin. In this short- and long-term efficacy trial, the responses of testosterone and its metabolites to the application of transscrotal testosterone systems of varying testosterone content were compared with the response to 200 mg of testosterone enanthate. Daily transscrotal testosterone system administration resulted in a rapid increase of testosterone and bioavailable, nonsex hormone binding globulin-bound testosterone levels to normal, peaking at two hours, followed by a slow decline over 23 hours, resembling the diurnal variation of endogenous testosterone. One year of daily transscrotal testosterone system therapy demonstrated continued reliable absorption of testosterone and suppression to normal of the luteinizing hormone in two of three patients. There was a greatly disproportionate increase of serum dihydrotestosterone over testosterone, suggesting 5-alpha reduction at the scrotal site. The subjects reported marked subjective improvement. Thus, the transscrotal testosterone system is a novel, effective, and well-tolerated method of delivering testosterone to hypogonadal patients.

Reproductive hormone responses to resistance exercise

To investigate if changes in circulating testosterone levels during isokinetic resistance exercise in women were similar to those during intense aerobic exercise and to examine concomitant changes in hemoconcentration, specific binding protein (sex hormone binding globulin-binding capacity), non-sex hormone binding globulin bound testosterone, luteinizing hormone, follicle-stimulating hormone, cortisol, and lactate, blood samples were obtained through an indwelling cannula at 30 and 15 min before exercise, after each of six exercises on upper and lower body muscle groups, and at 15 and 30 min after exercise in seven normal menstruating women. Investigations lasting approximately 60 min were performed in the early follicular phase beginning at 3.30 p.m. after two months of training with isokinetic ("Nautilus") equipment. Baseline testosterone and non-sex hormone binding globulin bound testosterone levels were significantly higher in subjects than in a control group. Increased total and non-sex hormone binding globulin bound testosterone was observed immediately prior to exercise with further increases late in exercise, then with proportional increases in cortisol and lactic acid. Sex hormone binding globulin-binding capacity increased before exercise. The testosterone increments exceeded hemoconcentration. Luteinizing hormone and follicle-stimulating hormone levels increased during exercise. The data suggest that origins of the exercise-associated testosterone increment are complex, resulting from hemoconcentration and specific gonadal and adrenal responses.