J. Montalto

Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males

A randomised crossover dietary intervention study was performed to evaluate the effects of replacing meat protein in the diet with a soyabean product, tofu, on blood concentrations of testosterone, dihydrotestosterone, androstanediol glucuronide, oestradiol, sex hormone-binding globulin (SHBG), and the free androgen index (total testosterone concentration/SHBG concentration x 100; FAI). Forty-two healthy adult males aged 35-62 years were studied. Diets were isoenergetic, with either 150 g lean meat or 290 g tofu daily providing an equivalent amount of macronutrients, with only the source of protein differing between the two diets. Each diet lasted for 4 weeks, with a 2-week interval between interventions. Fasting blood samples were taken between 07.00 and 09.30 hours. Urinary excretion of genistein and daidzein was significantly higher after the tofu diet (P < 0.001). Blood concentrations of sex hormones did not differ after the two diets, but the mean testosterone:oestradiol value was 10% higher (P = 0.06) after the meat diet. SHBG was 3% higher (P = 0.07), whereas the FAI was 7% lower (P = 0.06), after the tofu diet compared with the meat diet. There was a significant correlation between the difference in SHBG and testosterone:oestradiol and weight change. Adjusting for weight change revealed SHBG to be 8.8% higher on the tofu diet (mean difference 3 (95% CI 0.7, 5.2) nmol/l; P = 0.01) and testosterone:oestradiol to be significantly lower, P = 0.049). Thus, replacement of meat protein with soyabean protein, as tofu, may have a minor effect on biologically-active sex hormones, which could influence prostate cancer risk. However, other factors or mechanisms may also be responsible for the different incidence rates in men on different diets.

PLASMA C19 STEROID SULPHATE LEVELS AND INDICES OF ANDROGEN BIOAVAILABILITY IN FEMALE PATTERN ANDROGENIC ALOPECIA

Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA‐S), 5‐androstene‐3β, 17/β‐diol sulphate (5‐ADIOL‐S), 5α‐androstane‐3α, 17β‐diol sulphate (3α‐DIOL‐S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non‐SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 × T (nmol/1) ÷ SHBG (nmol/1), in premenopausal women with AA (n= 25‐45) and in normal premenopausal women (n= 17–73). While mean plasma concentrations of DHEA‐S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 ± 3 vs 64±3 nmol/1) and the mean free androgen index (4.4±0.4 vs 2.4±0–2), and mean concentrations of free testosterone (45 ± 5 vs 26 ± 1.4 pmol/ 1), non‐SHBG bound T (0.9 ±0.2 vs 0.6±0.1 nmol/1) and androstenedione (4.3±0.3 vs 3.4±0.2 nmol/1) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5‐ADIOL‐S (512±42 nmol/1) and 3a‐DIOL‐S (76±7 nmol/1) were significantly higher than levels found in normal women (272±12 nmol/1 and 52±2 nmol/1 respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5‐ADIOL‐S and 3α‐DIOL‐S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.

Cushing's syndrome in childhood and adolescence

Objective: To review the diagnosis, management and outcome of Cushings syndrome in children and adolescents.

Endocrinology and auxology of sibships with non-classical congenital adrenal hyperplasia.

The symptoms, auxological characteristics, and stimulated 17-hydroxyprogesterone (17-OHP) concentrations in a group of patients with non-classical 21-hydroxylase deficiency (NCCAH) were compared with those of their siblings. Ten index cases consisting of nine females and one male patient aged 3-33 years and 16 siblings were studied. In the sibling group five subjects were slightly virilised and of these, two females were found to have NCCAH according to their stimulated 17-OHP concentrations. The remaining nine siblings, who were not virilised, all had normal stimulated 17-OHP concentrations. Among the total NCCAH group (index cases and affected siblings) eight patients had the diagnosis made within two years of the onset of symptoms. In four patients diagnosis was delayed until adulthood. In seven patients investigated, bone age was significantly increased before treatment. The mean height and body mass index Z scores of the affected patients as a total group or when divided according to skeletal maturity were not significantly different from either the normal mean or from their unaffected siblings. Virilised siblings of patients with NCCAH should have stimulated 17-OHP levels measured to exclude the disease. Patients with NCCAH do not appear to be at risk of short adult stature despite increased bone age in childhood.

Diagnosis of 21‐hydroxylase deficiency in newborn infants by GC‐MS of urinary steroids

Abstract In a study using gas chromatography‐mass spectrometry (GC‐MS) on urine specimens from 16 normal infants and 16 infants with congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (aged 1 day to 4 weeks), the major steroids recognized in all infants were: 16α‐hydroxy‐dehydroepiandrosterone, 16β‐hydroxy‐dehydroepiandrosterone, 16‐oxo‐androstenediol, androstenetriol, 15β, 17α‐dihydroxy‐pregnenolone and 16α‐hydroxy‐pregnenolone.

Female androgenetic alopecia: An update

Androgenetic alopecia is an androgen dependent disorder occurring in genetically susceptible individuals. The pattern of hair loss in women differs from that of classical male pattern alopecia, being more diffuse and with retention of the frontal hair line in most cases. Characteristic histopathological changes occur but biopsy is rarely helpful in diagnosis. Although research has shown subtle alterations in the androgen status of women with androgenetic alopecia, most patients presenting with this disorder are normal endocrinologically. Anti‐androgen therapy will result in some improvement in up to 50% of patients after 6 to 12 months of therapy, but in practice will usually only decrease the rate of hair loss and not result in new hair growth.

Serum levels of 5-androstene-3β, 7β-DIOL sulphate, 5α-androstane-3α,17β-DIOL sulphate and glucuronide, in late onset 21-hydroxylase deficiency

Abstract Serum sulphates of 5-androstene-3β,17β-diol (5-ADIOL-S), 5α-androstane-3α,17β-diol (3α-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as 5α-androstane-3α,17β-diol glucuronide (3α-DIOL-G) and unconjugated androstenedione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI) and 17α-hydroxyprogester-ne (17OHP) were measured by specific radioimmunoassays (RIA) in 14 women with late-onset 21-hydroxylase deficiency (LOCAH), and in normal women ( n = 73). The diagnosis of LOCAH was made on the finding of a (17OHP) response level greater than 30 nmol/1 following ACTH stimulation, and/or an elevation of urinary metabolites of 17OHP. Mean values for serum concentrations of all steroids measured and the free androgen index (100 × T nmol/1 ÷ SHBG nmol/1) were significantly elevated, and SHBG levels depressed in patients with LOCAH. These studies show that in LOCAH, in addition to the unconjugated steroids AD and T, the sulphoconjugated steroids DHEA-S, 5-ADIOL-S and 3α-DIOL-S are increased, as is the glucuronide conjugate 3α-DIOL-G and the index of bioavailable testosterone (FAI), and that mean SHBG levels are depressed. These data suggest that as well as AD, 5-ADIOL-S and DHEA-S may act as pro-hormones for more potent steroids (T and 5α-dihydrotestosterone) in peripheral tissues, while 3α-DIOL-S and 3α-DIOL-G may both reflect peripheral androgen metabolism in patients with LOCAH.

Serum 5-androstene-3β,17β-diol sulphate, sex hormone binding globulin and free androgen index in girls with premature adrenarche

Abstract Serum sex hormone binding globulin (SHBG), testosterone (T), DHEA sulphate (DHEA-S), androstenedione (AD) and Δ5-androstene-3β,17β-diol sulphate (5-ADIOL-S) levels were measured by specific radioimmuoassay in 16 girls presenting with premature adrenarche (PA) and in 14 normal girls. Mean levels of steroids measured were significantly elevated, and SHBG significantly depressed, in the girls with PA, with values (mean ± SE) for DHEA-S (1.73 ± 0.17 vs 0.25 ± 0.06 μmol/l), 5-ADIOL-S (104 ± 8 vs 31 ± 4nmol/l), AD (0.89 ± 0.06 vs 0.62 ± 0.04 nmol/l), and T (0.49 ± 0.03 vs 0.23 ± 0.06 nmol/l). SHBG levels were 68 ± 6 vs 108 ±5 nmol/l, and the free androgen index [100 × T (nmol/l) ÷ SHBG (nmol/l)] was 0.89 ± 0.17 vs 0.22 ± 0.01. These studies show that SHBG is depressed in girls with premature adrenarche; with the increased testosterone levels, this results in a markedly elevated free androgen index, a measure of testosterone which is bioavailable to target tissue. This may be compounded by the elevated levels of 5-ADIOL-S in girls with PA since its role may be as a prohormone for more potent androgens (testosterone, 5α-dihydrotestosterone) in target tissues such as pubic skin.

CYP11β1 (11-beta-hydroxylase) deficiency in congenital adrenal hyperplasia

Objective: To review experience of CYP11β1 deficiency (previously known as 11β‐hydroxylase) at the Royal Childrens Hospital, Melbourne, Victoria.

Serum C-19 steroid sulphates in females with clinical hyperandrogenism.

Serum sulphates of 5-androstene-3 beta, 17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as unconjugated androstenedione (AD), testosterone (T) and 17 alpha-hydroxyprogesterone (17OHP), sex hormone binding globulin (SHBG) and the free androgen index (FAI) were measured by specific radioimmunoassay in girls with premature adrenarche (n = 9-16), and in hirsute women with (1) late onset 21 hydroxylase deficiency (n = 14), (2) polycystic ovarian disease (n = 28) and (3) idiopathic hirsutism (n = 74). Levels were also determined in females with androgenic alopecia (n = 35-45), in normal prepubertal girls (n = 9-14) and in normal adult women (n = 50-73). Mean serum concentrations of 5-ADIOL-S, 3 alpha-DIOL-S, DHEA-S, AD, T, and FAI were elevated and SHBG depressed, in all patient groups compared with controls, except for DHEA-S and T in patients with alopecia. We conclude that in addition to DHEA-S, 5-ADIOL-S may have a role as a pro-hormone in the synthesis of more potent androgens (T, DHT) in peripheral tissues such as skin; in addition, 3 alpha-DIOL-S may be a marker of peripheral androgen metabolism.