Concentrations Of Endogenous Steroids Research Articles

Testosterone and cardiovascular disease - a literature review

The effects of testosterone on the cardiovascular (CV) system make it a matter of scientific interest. Disturbances in endogenous steroid concentrations are some of the factors involved in the pathogenesis of atherosclerosis and ischemic heart disease. The aim of this article is to summarize the role of hypogonadism in the context of ischemic heart disease development and to review the current evidence on the CV benefits of testosterone replacement. Its low endogenous level is associated with worsened lipid profile, accelerated development of atherosclerotic plaques, high body mass index, metabolic syndrome and, type 2 diabetes mellitus. In light of these facts, some studies look into the benefits of exogenous testosterone replacement in patients with coronary heart disease and heart failure. The results are divergent and a large randomized trial is required to define the link between testosterone replacement therapy and CV risk. New clues present the recent data on the possible adaptive role of hypogonadism in acute coronary syndrome. This has the potential to expand the knowledge on the link between the CV system and gonadal function in men. The role of sex steroids in the pathogenesis of atherosclerotic heart disease and adaptation to acute coronary syndrome is a subject of increasing scientific interest as a result of accumulating evidence in this field.

Steroid profiling by UHPLC-MS/MS in dried blood spots collected from healthy women with and without testosterone gel administration

The quantification of a large panel of endogenous steroids in serum by LC–MS/MS represents a powerful clinical tool for the screening or diagnosis of diverse endocrine disorders. This approach has also demonstrated excellent sensitivity for the detection of testosterone misuse in the anti-doping field, especially in female athlete population. In both situations, the use of dried blood spots (DBS) could provide a viable alternative to invasive venous blood collection. Here, the evaluation of DBS sampling for the quantification of a panel of endogenous steroids using UHPLC-MS/MS is described.The UHPLC-MS/MS method was validated for quantitative analysis of eleven free and eight conjugated steroids and was then used for the analysis of DBS samples collected in 14 healthy women during a normal menstrual cycle (control phase) followed by a 28-days testosterone gel treatment (treatment phase). Results were compared with those obtained from serum matrix. Satisfactory performance was obtained for all compounds in terms of selectivity, linearity, accuracy, precision, combined uncertainty, stability as well as extraction recovery and matrix effects. In control phase, high correlation was observed between DBS and serum concentrations for most compounds. In treatment phase, higher testosterone concentrations were observed in capillary than in venous DBS, suggesting a possible interference resulting from testosterone contamination on finger(s) used for gel application.Steroid profiling in capillary DBS represents a simple and efficient strategy for monitoring endogenous steroid concentrations and their fluctuation in clinical context of steroid-related disorders, or for the detection of testosterone abuse in anti-doping.

Concentrations of nine endogenous steroid hormones in 70-year-old men and women.

ObjectivesCirculating concentrations of endogenous steroids have systemic implications on health in elderly. However, population-based age- and ethnicity-specific data are scarce. The aim was to report sex-specific plasma concentrations of endogenous sex and adrenal steroids in elderly Swedish Caucasians, to examine the impact of BMI and to present concentrations in apparently healthy subjects.MethodsA population-based observational study of 70-year olds, including 684 community-dwelling men and women enrolled in the PIVUS study, Sweden. Median plasma concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for pregnenolone, 17-hydroxypregnenolone, 17-hydroxy-progesterone, 11-deoxycortisol, DHEA, androstenedione, testosterone, estrone and estradiol.ResultsPlasma concentrations were significantly higher in men (n = 452) than in women (n = 232) for estradiol: median 61.3 pmol/L (95% CI, 11.4, 142.7) vs 18.4 (4.0, 127.3), for estrone: 92.8 (33.3, 206) vs 71.6 (17.8, 209) pmol/L, and for testosterone 13.8 (5.7, 28.0) vs 0.7 (0.2, 2.0) nmol/L. Higher concentrations of estrone and estradiol were observed in obese than non-obese women. Compared to non-obese men, obese men had lower concentrations of testosterone and its precursors: 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione and DHEA. The subgroup of apparently healthy individuals had median values > 20% lower for estrone and estradiol in women but slightly higher for testosterone in both sexes.ConclusionsConcentrations of estradiol, estrone and testosterone were higher in 70-year-old men than in women. BMI associated positively to estradiol and estrone in women and negatively to testosterone in men. Apparently healthy women had lower median concentrations of estradiol and estrone and men had higher median testosterone compared to all individuals.

Systemic Effects by Intrathecal Administration of Triamcinolone Acetonide in Patients With Multiple Sclerosis.

In patients suffering from multiple sclerosis (MS), intrathecal injection of triamcinolone acetonide (TCA) has been shown to improve symptoms of spasticity. Although repeated intrathecal injection of TCA has been used in a number of studies in late-stage MS patients with spinal cord involvement, no clinical-chemical data are available on the distribution of TCA in cerebrospinal fluid (CSF) or serum. Moreover, the effects of intrathecal TCA administration on the concentrations of endogenous steroids remain poorly understood. Therefore, we have quantified TCA and selected endogenous steroids in CSF and serum of TCA-treated MS patients suffering from spasticity. Concentrations of steroids were quantified by LC-MS, ELISA, or ECLIA and compared with the blood-brain barrier status, diagnosed with the Reibergram. The concentration of TCA in CSF significantly increased during each treatment cycle up to >5 μg/ml both in male and female patients (p < 0.001). Repeated TCA administration also evoked serum concentrations of TCA up to >30 ng/ml (p < 0.001) and severely depressed serum levels of cortisol and corticosterone (p < 0.001). In addition, concentrations of circulating estrogen were significantly suppressed (p < 0.001). Due to the potent suppressive effects of TCA on steroid hormone concentrations both in the brain and in the periphery, we recommend careful surveillance of adrenal function following repeated intrathecal TCA injections in MS patients.

The effect of athletes` hyperhydration on the urinary 'steroid profile' markers in doping control analysis.

The urinary 'steroid profile' in doping control analysis is a powerful tool aimed at detecting intra-individual deviations related to the abuse of endogenous steroids. Factors altering the steroid profile include, among others, the excessive fluid intake leading to low endogenous steroids concentrations compared to an individual's normal values. Cases report the use of hyperhydration by athletes as a masking method during anti-doping urine sample collection. Seven healthy physically active non-smoking Caucasian males were examined for a 72-hour period using water and a commercial sports drink as hyperhydration agents (20mL/kg body weight). Urine samples were collected and analyzed according to World Anti-Doping Agency (WADA) technical documents. Although, significant differences were observed on the endogenous steroid concentrations under the studied hyperhydration conditions, specific gravity adjustment based on a reference value of 1.020 can eliminate the dilution induced effect. Adjustment methods based on creatinine and urinary flow rate were also examined; however, specific gravity was the optimum method in terms of effectiveness to adjust concentrations close to the baseline steroid profile and practicability. No significant effect on the urinary steroid ratios was observed with variability values within 30% of the mean for the majority of data. Furthermore, no masking on the detection ability of endogenous steroids was observed due to hyperhydration. It can be concluded that any deviation on the endogenous steroid concentrations due to excessive fluid intake can be compensated by the specific gravity adjustment and therefore, hyperhydration is not effective as a masking method on the detection of the abuse of endogenous steroids.

Altered adrenal and gonadal steroids biosynthesis in patients with burn injury

IntroductionBurn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury. MethodsFor this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5–72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry. ResultsSteroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r=0.84), corticosterone (r=0.73), 11-deoxycortisol (r=0.72), androstenedione (r=0.72), 17OH-progesterone (r=0.68), 17OH-pregnenolone (r=0.64) and pregnenolone (r=0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury. ConclusionBurn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesis-driven study.

Detection and distribution of endogenous steroids in human stratum corneum

The objective of the study was to investigate the presence and distribution of endogenous steroids in human stratum corneum (SC) with respect to sex, age, anatomical site, and depth into SC, using a noninvasive sampling technique and a sensitive analytic method for quantitation. Corneocytes in the SC samples removed by sequential tape stripping from the forearm, forehead, and back sites were processed and analyzed using a validated liquid chromatography–tandem mass spectrometry method for the quantitation of hydrocortisone, cortisone, and testosterone. In the 32 volunteers surveyed, testosterone was only detected at the forearm site in a single volunteer. Both hydrocortisone and cortisone were detected in 5–7 individuals out of 16 from both the age 20–35 years and age 50–65 years groups. Maximal amounts of hydrocortisone and cortisone found in SC of forehead, forearm, and back were 0.37 ng/cm 2 , 0.96 ng/cm 2 , and 0.49 ng/cm 2 ; and 0.20 ng/cm 2 , 0.12 ng/cm 2 , and 0.06 ng/cm 2 , respectively, and were either higher than or comparable to those reported in human hair in terms of concentration by SC weight. In the population with either hydrocortisone or cortisone detected, no significant differences relating to sex, age groups, and anatomical sites were observed for the amount of hydrocortisone and cortisone in the SC. However, significantly higher amount of cortisone was found in the surface layers of SC than deeper layers in the age 50–65 years group. The results demonstrate that, with the achievable sensitivity of current analytical technology, physiological concentrations of endogenous steroids, such as hydrocortisone and cortisone, can be found in the SC of some individuals.

Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress

BackgroundDuring the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome.MethodsEleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children.ResultsCortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Higher concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone) were observed in the symptomatic state and the concentrations decreased after the recovery.ConclusionsPattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites (pregnanes) was found to be associated with the symptomatic state.

Advances in sports drug testing: An overview

Advances in sports drug testing: An overview

Chemical fate and biological effects of several endocrine disrupters compounds in two echinoderm species

Two echinoderm species, the sea urchin Paracentrotus lividus and the feather star Antedon mediterranea, were exposed for 28 days to several EDCs: three putative androgenic compounds, triphenyltin (TPT), fenarimol (FEN), methyltestosterone (MET), and two putative antiandrogenic compounds, p,p'-DDE (DDE) and cyproterone acetate (CPA). The exposure nominal concentrations were from 10 to 3000 ng L(-1), depending on the compound. This paper is an attempt to join three different aspects coming from our ecotoxicological tests: (1) the chemical behaviour inside the experimental system; (2) the measured toxicological endpoints; (3) the biochemical responses, to which the measured endpoints may depend. The chemical fate of the different compounds was enquired by a modelling approach throughout the application of the 'Aquarium model'. An estimation of the day-to-day concentration levels in water and biota were obtained together with the amount assumed each day by each animal (uptake in microg animal(-1) d(-1) or ng g-wet weight(-1) d(-1)). The toxicological endpoints investigated deal with the reproductive potential (gonad maturation stage, gonad index and oocyte diameter) and with the regenerative potential (growth and histology). Almost all the compounds exerted some kind of effect at the tested concentrations, however TPT was the most effective in altering both reproductive and regenerative parameters (also at the concentration of few ng L(-1)). The biochemical analyses of testosterone (T) and 17beta-estradiol (E(2)) also showed the ability of the selected compounds to significantly alter endogenous steroid concentrations.

Prepubertal Gynecomastia Linked to Lavender and Tea Tree Oils

Most cases of male prepubertal gynecomastia are classified as idiopathic. We investigated possible causes of gynecomastia in three prepubertal boys who were otherwise healthy and had normal serum concentrations of endogenous steroids. In all three boys, gynecomastia coincided with the topical application of products that contained lavender and tea tree oils. Gynecomastia resolved in each patient shortly after the use of products containing these oils was discontinued. Furthermore, studies in human cell lines indicated that the two oils had estrogenic and antiandrogenic activities. We conclude that repeated topical exposure to lavender and tea tree oils probably caused prepubertal gynecomastia in these boys.

Steroid levels in crinoid echinoderms are altered by exposure to model endocrine disruptors

Sexual steroids (testosterone and estradiol) were measured in the whole body of wild specimens of the crinoid Antedon mediterranea collected from the Tyrrhenian Sea (Italy). Testosterone levels (274–1488 pg/g wet weight (w.w.)) were higher than those of estradiol (60–442 pg/g w.w.) and no significant differences between males and females were observed. No clear seasonal trend was either detected – individuals from February, June and October 2004 analyzed – apart from a peak of estradiol in males in autumn. Nonetheless, dramatic changes on tissue steroid levels were observed when individuals were exposed to model androgenic and anti-androgenic compounds for 2 and 4 weeks. The selected compounds were 17α-methyltestosterone (17α-MT), triphenyltin (TPT), fenarimol (FEN), cyproterone acetate (CPA), and p, p′-DDE. Endogenous testosterone levels were significantly increased after exposure to 17α-MT, TPT and FEN, while different responses were observed for estradiol; 17α-MT and FEN increased endogenous estradiol (up to seven-fold), and TPT lead to a significant decrease. Concerning the anti-androgenic compounds, CPA significantly reduced testosterone in a dose-dependent manner without altering estradiol levels, whereas specimens exposed to p, p′-DDE at a low dose (24 ng/L) for 4 weeks showed a four-fold increase in T levels. Overall, the data show the ability of the selected compounds to alter endogenous steroid concentrations in A. mediterranea, and suggest the existence in this echinoderm species of vertebrate-like mechanisms that can be affected by exposure to androgenic and anti-androgenic chemicals.

Detection of norbolethone, an anabolic steroid never marketed, in athletes' urine.

Norbolethone (13-ethyl-17-hydroxy-18,19-dinor-17alpha-pregn-4-en-3-one) is a 19-nor anabolic steroid first synthesized in 1966. During the 1960s it was administered to humans in efficacy studies concerned with short stature and underweight conditions. It has never been reported by doping control laboratories. Norbolethone was identified in two urine samples from one athlete by matching the mass spectra and chromatographic retention times with those of a reference standard. The samples also contained at least one likely metabolite. The samples were also unusual because the concentrations of endogenous steroids were exceptionally low. Since norbolethone is not known to be marketed by any pharmaceutical company, a clandestine source of norbolethone may exist.

Effects of lactation length and an exogenous progesterone and estradiol-17β regimen during embryo attachment on endogenous steroid concentrations and embryo survival in sows

The hypotheses that short lactation lengths increase embryo mortality by altering endogenous post-weaning steroid concentrations, and that an exogenous steroid regimen during embryo attachment might increase embryo survival were tested using 36 s parity sows assigned randomly to a 2×2 factorial. Sows were subjected to either a short lactation (SL, 13.0 days, n=25) or a long lactation (LL, 31.5 days, n=11), artificially inseminated at first estrus and treated daily with 2 ml i.m. of either 25 mg progesterone (P 4) and 1.25 μg estradiol-17β (E 2) (steroid treatment, ST, n=17) or the vehicle alone (control treatment, CT, n=17) on Days 14–20 post-insemination. Blood samples were collected by jugular venipuncture from weaning to 24 days post-insemination on alternate days. Sows subjected to the SL compared to the LL tended to have a longer weaning-to-estrus interval (WEI) (5.3 versus 4.6 days; P<0.10), but did not have a significantly reduced conception rate (CR) (71 versus 90%; P>0.10). The SL and LL sows had a similar ovulation rate (19.9 versus 21.3 corpora lutea, CL; P>0.05), but SL sows had fewer viable embryos than LL sows (11.5 versus 15.3; P<0.05) when reproductive tracts were recovered 28–32 days post-insemination. In addition, even after correction for the difference in number of embryos between groups, viable embryos from the SL versus the LL group weighed less (1.63 versus 1.79 g; P<0.05), had a decreased amnion volume (1.02 versus 1.22 ml; P<0.05) and apparently produced less estrogens since estrone sulfate concentration was decreased at 24 days post-insemination in SL versus LL sows (4.3 versus 6.3 ng/ml; P<0.05). Embryo survival (percentage of CL represented by a viable embryo) however, was not different between SL and LL sows (60 versus 74%; P>0.05) and no differences in post-weaning P 4 or E 2 concentrations were apparent. Sows that received the ST only tended to have increased P 4 concentrations at 16 days post-insemination compared to CT sows and neither the number of viable embryos, nor embryo survival, was increased in ST versus CT sows (14.7 versus 12.2; P>0.05 and 66 versus 68%; P>0.05, respectively). These data suggest that short lactations do not increase embryo mortality by inducing aberrant endogenous post-weaning P 4 or E 2 concentrations. It is unclear whether or not small, repeated doses of exogenous P 4 and E 2 during attachment can increase embryo survival.

Endogenous Steroid Metabolism Is Indicated by Fluctuations of Endogenous Steroid and Steroid Glucuronide Levels in Early Development of the Steelhead Trout (Oncorhynchus mykiss)

Concentrations of endogenous steroids and their glucuronide conjugates fluctuated during early development in steelhead troutOncorhynchus mykiss.Whole body content of sex steroids and steroid glucuronides of both bisexual and gynogenetic (all female) steelhead trout were quantified by radioimmunoassay. Concentrations of 17β-estradiol (E2) and cortisol increased 2–4 days before hatch. Two days after hatch, 11-ketotestosterone (11KT) increased in concentrations in both gynogenetic and bisexual populations, and 11KT glucuronide concentrations increased in the gynogenetic population. Testosterone (T) and E2 concentrations were at their lowest at 39 days postfertilization (dpf) for T and 39 and 61 dpf for E2. Changes in levels of steroid glucuronides were not consistently parallel to free steroids through time. T−, E2−, and 17α, 20β dihydroxyprogesterone glucuronides declined slower than their free forms. Based on fluctuating concentrations of all steroid glucuronides, both populations of fish demonstrated an ability to form glucuronide conjugates of all steroids at the embryonic stage. The changes in levels of both free steroids and their glucuronides during early development of the trout indicate that steroid metabolism is active during development. This study also implicates steroid metabolism as an integral part of embryonic and postembryonic development.

Human placenta radioreceptor assay with digoxin and ouabain to detect endogenous digitalis-like factor(s) in human plasma and urine

We describe the optimization and validation of a clinically feasible radioreceptor assay to detect endogenous digitalis-like factor(s) (EDLF) in human plasma and urine. The assay is based on the competitive replacement of 125I-labeled digoxin on human placenta membranes by ligands present in sample extracts. Digoxin and ouabain were used as calibrators. We also describe simple and effective methods for extraction and enrichment of EDLF from human plasma and urine. Assay sensitivity and precision were enhanced by using a sequential saturation technique with appropriate concentrations of tracer and receptors. Filtration was used to separate bound from free ligand. A two-step solid-state extraction with acetonitrile allowed the separation of two EDLFs with different polarity (EDLF-1 and EDLF-2) from the same plasma sample. A one-step solid-state extraction with methanol was suitable for urine. EDLF-1 and EDLF-2 in healthy adults were respectively 204 +/- 155 and 207 +/- 423 pmol/L ouabain equivalents, or 312 +/- 241 and 302 +/- 581 pmol/L digoxin equivalents. Plasma concentrations of EDLFs in newborns and pregnant women were higher than in healthy adults, and the concentrations in urine were higher than in plasma. Several cross-reactivity experiments showed that physiological concentrations of endogenous steroids and lipids did not inhibit binding, and supported the hypothesis that EDLFs are endogenous compounds other than the steroids and lipids also investigated.

Mechanisms of physiological and pharmacological sex hormone action on the mammalian liver

Androgen and oestrogen receptors have been demonstrated in mammalian liver, but since it is generally accepted that they are probably non-functional at endogenous steroid concentrations, it is not apparent how they mediate physiological influences on this organ. Nor is it certain to what extent pharmacological actions of sex hormones reflect overstimulation of physiological routes or whether alternative mechanisms become available once threshold values have been reached. In this presentation an attempt has been made to answer some of these questions using data obtained from a study of the regulation of the activities of microsomal 3α-hydroxysteroid dehydrogenase (3α-HSDH) and 5α-reductase in rat liver. Androgens exert their primary physiological and pharmacological influences at the level of the hypothalamus. Oestrogens can elicit three different types of effect—physiological, antiandrogenic and pharmacological—of which the first two involve primary effects on the pituitary. Hepatic oestrogen receptors only become activated when oestrogen concentrations reach pharmacological levels. Progestins probably have no physiological influence on the livers of non-pregnant rats. Their pharmacological actions may either be traced back to secondary androgenic (e.g. medroxyprogesterone acetate, levonorgestrel) or oestrogenic (e.g. norethynodrel, lynestrenol) properties, involving the routes described above, or to independent effects on the central nervous system (e.g. cyproterone acetate modulation of 5α-reductase activity).

Dexamethasone suppresses pituitary-adrenal but not behavioral effects of centrally administered CRF

Intracerebral ventricular (icv) administration of corticotropin-releasing factor (CRF) significantly enhances the expression of stress related behaviors in the rat and also activates the pituitary-adrenal system. The pituitary-adrenal response can be blocked by pretreatment of animals with dexamethasone. The behavioral effects (motor activation, increased grooming and decreased eating) on the other hand are resistant to suppression by dexamethasone. The independence of the behavioral effects from activation of the pituitary-adrenal axis suggests that stress-induced release of CRF could contribute to behavioral alterations even in the presence of high concentrations of endogenous steroids.

Factors affecting the reproducibility of androgen receptor determinations in human prostate

Several factors affecting the reproducibility of androgen receptor assays in the human prostate gland have been identified. Experiments in the presence of proteolytic inhibitors such as PMSF, leupeptin and aprotinin resulted in no change in the estimates of androgen receptors. The androgen binding was also unaffected by the concentrations of endogenous steroids in the tissue. Although the receptor assay was reliable down to protein concentrations of about 5 g/l, at lower concentrations the reliability of the method was significantly reduced. Similarly, tissue storage at −25°C drastically lowered the binding capacity of the prostatic tissue extracts to 50% of initial receptor content over a period of 3 months. The high degree of correlation between receptor levels in the stroma and epithelium suggests that the binding in the total gland will not be drastically affected by the proportion of stroma and epithelium it contains. Following the widely practised 2-h extraction of the nucleus with 0.6 mol/1 KCl buffer, a highly significant non-extractable binding component remained. Analysis of data by the single-point assay produced results comparable to those obtained by standard Scatchard analysis and seemed reliable so long as careful quality control was employed.

Production rates of androgens and oestrogens in post-menopausal women

The production rate (PR) values of Δ 4-androstenedione (A), testosterone (T), oestrone (E l) and oestradiol (E 2) have been determined in a large group of post-menopausal women following constant infusions of radiolabelled hormones and radioimmunoassay of endogenous steroid concentrations. The mean ± SE age was 64 ± 2 yr, ranging from 46 to 91 yr and the mean ± SE weight was 144 ± 4lb. When the PR values were related to age by linear regression analysis no significant correlation could be found for PRA, PRT or PRE 1 and the age of the subjects. There was, however, a significant correlation between PRE 2 and age. There was a significant correlation between the PR values for each of the four steroids and the weights and body surface areas of the subjects. In addition, PRA correlated directly with both PRT and PRE 1 in these subjects in which both PR values were measured. The PR values for each steroid were significantly smaller in the post-menopausal women compared to the mean PR values of a large group of pre-menopausal women. We conclude that age, per se, does not appear to influence the PR values for A, T and E 1 but does for E 2. The subject's weight, however, has a major influence for the PR values of all four steroids.