Androgen receptors in the pubic skin and testosterone content of the blood in women with hirsutism

A study was made of "free" binding sites and the total number of sites binding androgens with the cytoplasmic receptor protein in the pubic skin biopsy specimens and testosterone in the blood serum of patients with hirsutism, degree II-III. A higher mean level of testosterone was found in the blood serum of patients with hirsutism, degree II-III, suffering from hyperandrogenism of ovarian and/or adrenal origin as compared to women with idiopathic hirsutism, degree I-III. "Free" sites of the binding of 5 alpha-dihydrotestosterone (DHT) with receptors were not revealed in most of the patients, however the total number of sites of the binding of DHT with cytoplasmic receptors were found in all the studied skin biopsy specimens. The results obtained show that there are significant differences in the testosterone level in the blood serum and the total number of DHT binding sites in the pubic skin cytosol of women with idiopathic hirsutism and patients with hirsutism, degree II-III, with hyperandrogenism of ovarian and/or adrenal origin.     

Salivary testosterone levels in women with systemic lupus erythematosus

Objective. To measure salivary testosterone in women with systemic lupus erythematosus (SLE). Methods. We investigated concentrations of salivary testosterone in 13 women with active SLE and 47 women with inactive SLE, and in 72 healthy female controls. Results. We found a significant decrease in salivary testosterone concentrations in glucocorticoid-treated SLE patients (mean ± SD 0.06 ± 0.04 nmoles/liter) but no differences in concentrations in untreated patients (0.09 ± 0.03 nmoles/liter), compared with the healthy controls (0.11 ± 0.04 nmoles/liter). Conclusion. Glucocorticoid treatment appears to cause a decrease in the salivary testosterone level. Measurement of salivary testosterone is a simple way of monitoring androgen metabolism in patients with SLE.     

Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism

CONTEXT: Hirsutism (i.e. facial and body terminal hair growth in a male-like pattern in women) is the principal clinical sign of hyperandrogenism, although its definition remains unclear. OBJECTIVE: The purposes of the present study were to define 1) the degree of facial and body terminal hair, as assessed by the modified Ferriman-Gallwey (mFG) score, in unselected women from the general population; 2) the effect of race (Black and White) on the same; and 3) the normative cutoff values. DESIGN AND SETTING: We conducted a prospective observational study at a tertiary academic medical center. PATIENTS/PARTICIPANTS: Participants included 633 unselected White (n = 283) and Black (n = 350) women presenting for a preemployment physical exam. INTERVENTIONS: Interventions included history and physical examination. MAIN OUTCOME MEASURES: Terminal body hair growth was assessed using the mFG scoring system; nine body areas were scored from 0-4 for terminal hair growth distribution. RESULTS: The mFG scores were not normally distributed; although cluster analysis failed to identify a natural cutoff value or clustering of the population, principal component and univariate analyses denoted two nearly distinct clusters that occurred above and below an mFG value of 2, with the bulk of the scores below. Overall, an mFG score of at least 3 was observed in 22.1% of all subjects (i.e. the upper quartile); of these subjects, 69.3% complained of being hirsute, compared with 15.8% of women with an mFG score below this value, and similar to the proportion of women with an mFG score of at least 8 who considered themselves to be hirsute (70.0%). Overall, there were no significant differences between Black and White women. CONCLUSIONS: Our data indicate that the prevalence and degree of facial and body terminal hair growth, as assessed by the mFG score, is similar in Black and White women and that an mFG of at least 3 signals the population of women whose hair growth falls out of the norm.     

Salivary testosterone levels in women with systemic lupus erythematosus.

OBJECTIVE. To measure salivary testosterone in women with systemic lupus erythematosus (SLE). METHODS. We investigated concentrations of salivary testosterone in 13 women with active SLE and 47 women with inactive SLE, and in 72 healthy female controls. RESULTS. We found a significant decrease in salivary testosterone concentrations in glucocorticoid-treated SLE patients (mean +/- SD 0.06 +/- 0.04 nmoles/liter) but no differences in concentrations in untreated patients (0.09 +/- 0.03 nmoles/liter), compared with the healthy controls (0.11 +/- 0.04 nmoles/liter). CONCLUSION. Glucocorticoid treatment appears to cause a decrease in the salivary testosterone level. Measurement of salivary testosterone is a simple way of monitoring androgen metabolism in patients with SLE.     

Normal and elevated 3 alpha-androstanediol glucuronide concentrations in women with various causes of hirsutism and its correlation with degree of hirsutism and androgen levels.

We investigated peripheral androgen metabolic activity in 54 hirsute females (HF) by evaluating the serum 3 alpha-androstanediol glucuronide (3AG) concentration, hirsutism score (HS), and etiology of hirsutism. Based on basal and ACTH-stimulated steroid profiles (1 h post-Cortrosyn, 0.25 mg, i.v. bolus), the causes of hirsutism were determined to be increased adrenal androgen production (greater than 2 SD above normal mean), increased ovarian testosterone (T) production (greater than 2 SD above normal mean basal T of ovarian source only), or idiopathic cause (normal steroid profile). Serum 3AG levels in each group of HF were significantly higher (P less than 0.01-0.001) than those in normal females [normal: 2.9 +/- 0.94 nmol/L (n = 28); HF: increased adrenal androgen production of undefined cause, 7.7 +/- 7.5 nmol/L (n = 14); 21-hydroxylase deficiency, 7.6 +/- 7.4 nmol/L (n = 5); increased ovarian T production 5.5 +/- 3.5 nmol/L (n = 18); idiopathic cause, 5.8 +/- 4.8 nmol/L (n = 17)]. However, normal 3AG levels (less than 5.2 nmol/L) were present in 50-67% of HF in each group. Collectively, 3AG levels in HF correlated significantly (P less than 0.01) with dehydroepiandrosterone (DHEA; r = 0.41) and DHEA sulfate (DS; r = 0.44), while the correlation with androstenedione (r = 0.15) or T (r = 0.19) was not significant. Serum 3AG and adrenal androgen levels decreased in all subjects after dexamethasone treatment (0.5-1 mg at hour of sleep; 2 mg/day for 3-5 days). The correlation between 3AG and HS was significant (r = 0.6-0.74; P less than 0.01-0.001) only in HF with increased adrenal androgen secretion and idiopathic cause, and was not significant (r = 0.42) in HF with increased ovarian T secretion. There was no significant correlation between androgen levels and HS. We conclude that the serum 3AG level was not consistently elevated in HF and did not differ significantly between the various causes. Significant correlations between 3AG and DHEA/DS levels, and the simultaneous decrease in 3AG and adrenal androgens after dexamethasone administration in HF suggest that adrenal androgens contribute significantly to 3AG production. The significant correlation between 3AG and HS in HF with increased adrenal androgen secretion and idiopathic cause indirectly suggests an adrenal androgen contribution to both 3AG production and hirsutism in these HF. The insignificant correlation between 3AG and HS in HF with increased ovarian T secretion may result from a confounding effect of ovarian T on hirsutism.     

Effect of leuprolide and dexamethasone on hair growth and hormone levels in hirsute women: the relative importance of the ovary and the adrenal in the pathogenesis of hirsutism

Ten hirsute women with polycystic ovarian syndrome (PCO) and nine with idiopathic hirsutism (IH) underwent selective ovarian suppression with leuprolide for 5-6 months and then were randomized to receive, in addition, dexamethasone or placebo for 4 more months. Serum hormone levels and hair growth rates were determined before and after each treatment period. During the initial treatment period with leuprolide alone, testosterone decreased by 54 +/- 6% (mean +/- SEM) in PCO and by 36 +/- 3% in IH (P = 0.02). Androstenedione decreased by 53 +/- 6% in PCO and by 31 +/- 7% in IH (P = 0.02). Androstanediol glucuronide (Adiol-G) decreased by 14 +/- 6% in PCO and by 7 +/- 3% in IH. There was no change in dehydroepiandrosterone sulfate (DHEAS). While initial serum androgen levels were higher in PCO than in IH, they were similar after ovarian suppression in the two groups. After ovarian suppression, Adiol-G was more consistently correlated with testosterone and androstenedione than was DHEAS, suggesting that Adiol-G may be a better marker than DHEAS of adrenal androgen secretion. Hair growth rates decreased by 37 +/- 6% in PCO and by 14 +/- 10% in IH (P = 0.07). The change in hair growth correlated with the change in androstenedione (r = 0.66; P = 0.002), but not significantly with the change in testosterone (r = 0.29; P = 0.2). After the addition of dexamethasone therapy (0.5 mg daily), testosterone, androstenedione, and DHEAS levels fell to near or below assay detection limits, while Adiol-G decreased by 80 +/- 3%. Hair growth rates decreased slightly more in women during dexamethasone (46 +/- 6%) than during placebo (26 +/- 9%; P = 0.18). In summary, the ovary was the major source of circulating testosterone and androstenedione in PCO. The adrenal contributed a substantial minority of these hormones in PCO and was the major source of androgen secretion in IH. Adrenal hyperandrogenism was common in both IH and PCO. Hair growth rates correlated best with changes in serum androstenedione levels. Adiol-G, which was derived primarily from adrenal precursors, was a better marker of adrenal androgen secretion than was DHEAS in these subjects.     

Salivary testosterone: a reliable approach to the diagnosis of male hypogonadism

OBJECTIVE: This study was to demonstrate that Sal-T is a reliable biomarker of androgen status in the diagnosis of male hypogonadism. DESIGN: In order to validate the salivary testosterone assay (Sal-T), its reproducibility, the agreement with serum free testosterone levels (Free-T), the correlation with other circulating androgen markers (bioavailable testosterone, total testosterone) and cut-off values were defined. PATIENTS AND METHODS: We studied 52 eugonadic (E) and 20 hypogonadic (Hy) men. Sal-T was assayed using an adapted radioimmunoassay for serum testosterone. Sal-T concentrations were compared in nine cases before and after citric acid stimulation of salivary flow rate. Free-T and bioavailable testosterone (Bio-T) were calculated by Vermeulen equation and SHBG were determined by binding assay. RESULTS: Sal-T did not depend on salivary flow rate and morning samples from 07.00 h to 09.00 h were stable. Agreement between Sal-T and Free-T measurements was confirmed in all subjects. Sal-T levels correlated positively with all circulating androgens, showing the best correlation with Free-T in E (r = 0.92) as well as in Hy (r = 0.97). A cut-off value of Sal-T < or = 0.195 nm showed 100% sensibility and specificity to rule out hypogonadism. CONCLUSIONS: Our data showed that Sal-T is a reliable marker of testosterone bioavailability. The results support the inclusion of this biomarker as a noninvasive approach in the diagnosis of male androgen deficiency.     

Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone

Older men, particularly those with low serum testosterone (T) levels, might benefit from T therapy to improve bone mineral density (BMD) and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men. We hypothesized that the combination of T and finasteride (F), a 5 alpha-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate. Seventy men aged 65 yr or older, with a serum T less than 12.1 nmol/liter on two occasions, were randomly assigned to receive one of three regimens for 36 months: T enanthate, 200 mg im every 2 wk with placebo pills daily (T-only); T enanthate, 200 mg every 2 wk with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not an inclusion criterion. We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry. Prostate-specific antigen (PSA) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate. Fifty men completed the 36-month protocol. By an intent-to-treat analysis including all men for as long as they contributed data, T therapy for 36 months increased BMD in these men at the lumbar spine [10.2 +/- 1.4% (mean percentage increase from baseline +/- SEM; T-only) and 9.3 +/- 1.4% (T+F) vs. 1.3 +/- 1.4% for placebo (P < 0.001)] and in the hip [2.7 +/- 0.7% (T-only) and 2.2 +/- 0.7% (T+F) vs. -0.2 +/- 0.7% for placebo, (P < or = 0.02)]. Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip. After 6 months of therapy, urinary deoxypyridinoline (a bone-resorption marker) decreased significantly compared with baseline in both the T-only and T+F groups (P < 0.001) but was not significantly reduced compared with the placebo group. Over 36 months, PSA increased significantly from baseline in the T-only group (P < 0.001). Prostate volume increased in all groups during the 36-month treatment period, but this increase was significantly less in the T+F group compared with both the T-only and placebo groups (P = 0.02). These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months, both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men. In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy. These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels.     

Fetal programming of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone

We examined effects of dietary soy protein isolate (SPI) or genistein (GEN; soy isoflavone) during pregnancy on development of colon cancer in male progeny Sprague-Dawley rats. Four groups of rats were used: a lifetime casein-fed group (CAS; control diet), a lifetime SPI-fed group (positive control for protective effect of diet on colon carcinogenesis), a group whose dams received SPI only during pregnancy and CAS thereafter (SPI/CAS), and a group whose dams received CAS+GEN only during pregnancy and CAS thereafter (GEN/CAS). At 47 and 55 days of age, male progeny were administered the intestinal carcinogen azoxymethane (AOM). Tumors, endocrine status, and colon gene expression were evaluated at 20 week post-AOM. The SPI group had 47% decreased colon tumor incidence compared with the CAS group (P<0.05), whereas SPI/CAS, GEN/CAS, and CAS groups did not differ in this regard. Maternal-only SPI increased the percentage of animals bearing multiple colon tumors (P<0.05), an effect not mimicked by GEN. Serum insulin and leptin concentrations were decreased by lifetime SPI (P<0.05), whereas serum IGF-I was elevated in the SPI/CAS group (P<0.05). The SPI/CAS group had reduced serum testosterone levels (P<0.05) and exhibited a tendency for increased mucosal expression of IGF-I receptor and glucose transporter-1 mRNAs. Results indicate an effect of dietary protein type during pregnancy on colon tumor multiplicity and colon tissue gene expression, and serum IGF-I and testosterone in progeny rats as later adults.