The relationship of sex hormones to hyperinsulinemia and hyperglycemia.

Mexican-Americans, a high-risk population for non-insulin-dependent diabetes mellitus (NIDDM), have been previously reported to have decreased levels of sex-hormone-binding globulin (SHBG). We measured total testosterone, total estradiol and SHBG, glucose and insulin in premenopausal women (58 Mexican-Americans and 38 non-Hispanic whites) as part of the San Antonio Heart Study, a population-based study of cardiovascular risk factors. Although total estradiol and total testosterone were, in general, not correlated with metabolic variables, SHBG was negatively correlated with glucose and insulin. After adjustment for body mass index (BMI), ratio of waist-to-hip circumference (WHR) and ratio of subscapular-to-triceps skinfold (Centrality Index), SHBG was still significantly correlated with insulin concentrations (P less than .001). Since Mexican-Americans were previously reported to be more hyperinsulinemic than non-Hispanic whites, we examined the effect of adjusting for SHBG on insulin levels in this small population. While unadjusted insulin concentrations in Mexican-Americans were higher than in non-Hispanic whites (354 microU/mL v 236 microU/mL, respectively, P = .009), adjustment for BMI, WHR, and centrality index reduced the ethnic difference in insulin levels considerably (P = .014). However, only after adjusting for SHBG as well, did the ethnic difference in insulin levels became nonsignificant. Our data suggest that alterations in sex hormones and SHBG in particular may be related to the hyperinsulinemia and the high rates of NIDDM in Mexican-Americans.

Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3.

Plasma testosterone (T) and sex hormone binding globulin (SHBG) were assayed in normal controls (N = 9) and hypothyroid patients (N = 17) receiving increasing doses of L-T4 (0.2 mg, 0.4 mg for 30 days), followed first by 30 days without medication and then by 30 days each of 0.05 mg L-T3 and 0.2 mg L-T3. Normal male controls showed a significant increase in plasma T only at high doses of either L-T4 (0.4 mg) or L-T3 (0.2 mg). A small but significant increase in plasma T levels was observed in normal female subjects at 0.4 mg of T4. In both men and women, plasma SHBG increased in a dose-dependent manner with L-T4 or L-T3 and correlated positively and significantly with serum thyroid hormone levels. Hypothyroid male subjects had significantly lower levels of plasma T (mean +/- SD) of 279 +/- 131 ng/dl as compared with normal males (431 +/- 118 ng/dl), which reached the normal range only at a relatively high dose of either L-T4 (0.4 mg) or L-T3 (0.2 mg). No significant changes in plasma T were seen in the hypothyroid female group. Basal plasma SHBG levels were significantly lower in both hypothyroid men and women and increased towards normal levels during L-T4 and L-T3 therapy, although the response to thyroid hormones was significantly lower than that of normal controls. These results indicate that thyroid hormone therapy increases plasma SHBG levels in both normal and hypothyroid patients and that this increase precedes the expected elevation of plasma T in males.

Steroid and steroid regulating hormones in human male castrates.

Testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone and its sulphate, 11 beta-hydroxyandrostenedione, 17 alpha-hydroxyprogesterone, cortisol, LH, FSH and sex hormone binding globulin (SHBG) were determined in 16 otherwise healthy male castrates, orchidectomized for the forensic reasons. Their hormone levels were compared with those, obtained in normal males of the same age category. There were found in the castrates decreased levels of testosterone, dihydrotestosterone, dehydroepiandrosterone sulphate and androstenedione, unaltered concentrations of cortisol and dehydroepiandrosterone, whereas the levels of 11 beta-hydroxyandrostenedione, 17 alpha-hydroxyprogesterone, both gonadotrophins and SHBG were increased. The results point to the importance of the selective increase of the incretory activity of the adrenal cortex in situations, when the gonadal function is impaired or missing.

Lead toxicity on endocrine testicular function in an occupationally exposed population.

The hypothalamo-pituitary-testicular axis was evaluated in a group of 23 men who worked in the lead smelting industry and had a history of occupational inorganic lead exposure. The endocrine status of the workers was related to lead poisoning biological markers. According to the duration of their lead exposure they were divided into three groups: group 1 less than 1 year, n = 5; group 2 between 3 and 5 years, n = 8; group 3 greater than 5 years, n = 10. Serum testosterone (T), steroid binding globulin (SBG), free testosterone index (T/SBG), serum luteinizing hormone (LH), follicle stimulating hormone (FSH), Blood lead levels, and blood zinc protoporphyrin (ZPP) were measured in all workers. Groups 2 and 3 showed a decrease in serum testosterone levels, an increase in SBG levels, and a decrease in T/SBG index, suggesting a correlation between testicular dysfunction and duration of exposure. There was an increase in serum LH in group 1, which was not progressive. This suggests that prolonged lead exposure initially produces a direct testicular toxicity followed by hypothalamic or pituitary disturbance when longer periods of exposure take place.

Effect of oestrogen and progestagen on gonadotrophins and sex hormones in oophorectomized women.

Five premenopausal women were followed with measurements of androgens, oestrogens, gonadotrophins and sex hormone binding globulin (SHBG) after ovariectomy for benign disease. After a period of 6 weeks without treatment the women were treated with oestradiol 4 mg daily for 8 weeks, oestradiol 4 mg plus norethisterone acetate (NETA) 2 mg daily for 8 weeks and finally oestradiol 4 mg daily for another 8 weeks. The levels of androgens did not change during the various periods. As usual during oral treatment oestrone and oestrone sulphate were elevated while oestradiol levels were in the pre-operative range during treatment, regardless of the addition of NETA. SHBG was elevated during oestrogen-only treatment, while addition of NETA normalized the concentration of SHBG. In the combined NETA period concentrations of free oestradiol and non-SHBG-bound oestradiol were significantly elevated, and gonadotrophins returned to premenopausal levels, in contrast to the high levels in the oestrogen-only periods. Using oral oestrogen therapy it may be preferable to add a progestagen rather than elevate the oestrogen dose. Progestagen will result in more free oestradiol and give greater relief of symptoms, but the potentially harmful effect of progestagens on blood lipids must be considered.

Hormonal abnormalities in obesity.

We have found a number of interesting hormonal abnormalities in obese men and women: 1) Obese women have normal levels of estrone, total estradiol, and total testosterone, but as a consequence of their subnormal levels of SHBG, their levels of free estradiol and free testosterone are significantly elevated. 2) Massive weight loss in obese women (to still elevated weight) results in normalization of the previously elevated free estradiol and free testosterone. 3) Obese women have normal plasma DHEA levels, but a significant, age-invariant decrease of the plasma DHEA/T ratio, which could be due to increased tissue activity of 3 beta-hydroxysteroid dehydrogenase. 4) Massive weight loss produces an age-dependent effect on DHEA levels in obese women: the levels increase to supranormal values in women around age 20, with diminishing increases at higher premenopausal ages and no increase at all at perimenopausal age. 5) Obese men have elevated levels of estrone and both free and total estradiol, and subnormal levels of free and total testosterone and of FSH; all these abnormalities are proportional to the degree of obesity. They also have relatively subnormal LH levels, i.e. normal in the face of hypotestosteronemia. The combination of these findings represents a state of mild hypogonadotropic hypogonadism (HHG), which we believe to be induced by the hyperestrogenemia. 6) Normalization of the estrogen levels of obese men, by suppression of adrenocortical secretion of aromatase substrates or by inhibition of aromatase, tends to normalize the HHG. 7) Massive weight loss in obese men normalizes their HHG without any decrease in plasma estrogen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related changes in plasma dehydroepiandrosterone sulphate, cortisol, testosterone and free testosterone circadian rhythms in adult men.

The circadian rhythms of serum luteinizing hormone, follicle-stimulating hormone, testosterone (T), free testosterone (fT), sex hormone-binding globulin (SHBG), oestradiol, cortisol and dehydroepiandrosterone sulphate (DHA-s) have been investigated in 5 normal male adults and 6 elderly men. Circadian rhythms were detected statistically significant (p less than 0.05) by population mean cosinor analysis, for T, fT, cortisol and DHA-s in the young group. In the elderly population, serum cortisol showed a clear circadian rhythm, although with some phase modification, whereas DHA-s secretion lost its circadian rhythmicity. This demonstrates that ageing differently affects the two major adrenal functions, glucocorticoid and androgenic; further, the data suggest that an independent adrenal androgen-regulating system could be selectively impaired in the older subjects. In the elderly group the loss of T circadian rhythm was confirmed, but a statistically significant circadian rhythm of fT was recorded. It was characterized by a marked phase advance and not related with the SHBG modifications found in elderly men. This finding leads us to reconsider the role of fT, which appears more sensitive than total T, in studying circadian rhythm of gonadal androgen secretion.

The effect of nutritional factors on sex hormone levels in male twins.

Dietary intake has been hypothesized as being associated with several hormonally related cancers including prostate, breast, ovarian, and endometrial cancer. Because diet may affect hormones directly, it is logical to examine the effects of dietary factors on hormone production and levels. Therefore, a set of 72 male MZ and 83 male DZ twin pairs was ascertained from the Utah birth certificates. A quantitative food frequency questionnaire was administered and blood samples were drawn for hormonal assays. Heritability estimates for hormonal levels were calculated indicating a range from no heritability for sex hormone binding globulin (SHBG), estrone, and testosterone glucuronide to 70% for androstanediol glucuronide and luteinizing hormone. To examine nutritional factors, the difference in hormone and SHBG levels between each MZ twin and his co-twin were correlated with the difference in nutrient intake. Weight and obesity were significantly correlated with plasma testosterone and follicle stimulating hormone. Fat intake showed a significant association with testosterone. Androstanediol glucuronide, a steroid that reflects tissue formation of dihydrotestosterone, was inversely correlated with caloric intake, theobromine and caffeine. Testosterone glucuronide exhibited significant correlations with calories and vitamin A. This study suggests that dietary intake affects plasma sex-steroid levels in men.

Progestagen-dependent effect on some plasma proteins during oral contraception.

Seventeen healthy women received a combination of 0.030 mg of ethinyl estradiol and 0.150 mg of levonorgestrel or a combination of 0.030 mg of ethinyl estradiol and 0.150 mg of desogestrel for 2 years as oral contraception. Serum levels of sex hormone binding globulin, transcortin, ceruloplasmin, and pregnancy-associated protein were measured before contraception, during 3, 6, 12, 18, and 24 months of treatment, and 2 months after stopping the pill. Oral contraception with both preparations induced a similar, significant rise in both ceruloplasmin and pregnancy-associated protein. Sex hormone binding globulin levels rose significantly with the ethinyl estradiol-desogestrel, but not with the ethinyl estradiol-levonorgestrel combination. Transcortin increased with both preparations, more with the ethinyl estradiol-desogestrel combination.

Effects of combined ethinylestradiol and desogestrel on hormone profiles and sex hormone binding globulin in women with polycystic ovarian disease.

A longitudinal study to determine the effects of combined ethinylestradiol (EE) and desogestrel (DG) on hormone profiles and levels of sex hormone binding globulin (SHBG) were carried out in 19 Thai women with polycystic ovarian disease (PCOD). Evaluations were performed before and after 3 and 6 cycles of treatment. Regularity of cycles was observed in all patients. Most of them had improvement of androgenic symptoms. Body weight decreased slightly after 6 cycles of treatment. During the treatment course, serum luteinizing hormone (LH), testosterone (T), free T and dehydroepiandrosterone sulfate decreased significantly. Serum follicle stimulating hormone (FSH) and prolactin levels did not change. LH-to-FSH ratio markedly decreased. SHBG level increased to the control level. After discontinuation of the pill, menstrual disturbances recurred in all patients. It appears that low-dose combined OCs containing DG is suitable for use in women with PCOD. However, long-term treatment may be needed since the abnormal menstrual pattern returned after stopping the pill.

Diagnosis of amiodarone-iodine-induced thyrotoxicosis(AIIT) associated with severe nonthyroidal illness.

A rare case of amiodarone-iodine-induced thyrotoxicosis (AIIT) associated with nonthyroidal illness is reported. Serum total thyroxine (TT4) and free T4 (FT4) concentrations were elevated and serum TSH was undetectable as frequently observed also in euthyroid amiodarone-treated patients. At variance with common forms of AIIT, serum total triiodothyronine (TT3) was reduced due to low-T3 syndrome. The laboratory diagnosis was made on the basis of elevated free T3 (FT3) levels. Thus, in patients with severe nonthyroidal illness submitted to chronic amiodarone treatment, thyroid status can only be determined by free hormone measurement, particularly FT3 in the case of thyrotoxicosis.

Inverse seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity.

The effects of season on the activity of the pituitary-ovarian axis and the pineal gland were studied in 11 women by serum and urinary melatonin determinations and in 21 women by measurements of the serum concentrations of anterior pituitary and ovarian hormones during the dark and light seasons. A melatonin index was determined by integration of the area below the curve of serum melatonin concentrations during 24-h periods in both seasons. During the dark season, the daytime 12-h melatonin index and daytime urinary melatonin excretion were significantly higher than during the light season. In addition, the duration of the nocturnal melatonin pulse (serum melatonin levels, greater than 65 pmol/L) was lengthened during this season, whereas the mean serum estradiol concentration was significantly decreased at the time of ovulation and during the luteal phase of the cycle, indicating lowered ovarian activity. Luteal phase gonadotropin concentrations were increased during the dark season, which was also characterized by increased sex hormone-binding globulin (SHBG) and decreased free testosterone concentrations and free androgen indices (ratio of testosterone to SHBG X 700) throughout the menstrual cycle. The dark season was thus characterized by increased melatonin secretion and decreased ovarian and androgenic activities. In summary, we characterized two season-dependent hormonal phenomena. Although we did not prove any cause and effect association between melatonin and anterior pituitary-ovarian hormones, the inverse seasonal relationship in pineal gland and ovarian secretion suggests that melatonin is causally related to reproduction in humans.

A new low-dose estrogen oral contraceptive combination: effect on endocrine parameters and lipid status.

In this study the variations of endocrine and metabolic parameters of 39 women treated with a new oral contraceptive combination containing 20 mcg of ethinylestradiol and 150 mcg of desogestrel were examined. Gonadotropins and androgen presented a significant decrease, showing the efficiency of suppression of the pituitary-ovarian activity and of the contraceptive effect. The significant increase of SHBG and the corresponding reduction of free testosterone reflect the estrogenic environment of this pill and the low androgenicity of desogestrel. During the observation period, plasma levels of total cholesterol, trglycerides, LDL-C and HDL2-C were not altered, whereas total phospholipids, HDL-C and HDL3-C increased significantly. Besides a general positive effect on the main lipid parameters involved in atherogenic process, this pill also presented an optimal subjective tolerability.

Effect of Anordrin on serum levels of sex hormone binding globulin, caeruloplasmin and ovarian function.

Ten doses of 7.5 mg Anordrin were administered on alternate days from day 5 of the menstrual cycle to 20 women. Serum concentrations of both SHBG and CP were significantly increased after the fourth dose but the increases were minor compared to those produced by ethynyloestradiol. Two weeks after stopping Anordrin, serum concentrations of the proteins were still elevated in most women. Ovarian activity was studied in 8 women; serum oestradiol and progesterone concentrations indicated that ovulation occurred at the normal time in three women but was delayed for two weeks or more in the remaining five. The findings suggest that in humans, Anordrin acts as a weak oestrogen and may also have antioestrogenic activity.