Testosterone and Glucose Homeostasis in Adult Males: Current Insights and Future Prospects.

Insulin plays a central role in blood glucose regulation, with insulin resistance contributing to the progression of prediabetes to diabetes, underscoring the importance of early intervention. Androgens, primarily synthesized in the testis under pituitary gland influence, impact male reproductive function. Testosterone, crucial for sexual development and secondary male characteristics, declines with age, leading to issues like anemia, sexual dysfunction, and reduced bone density. Sex-specific differences in glucose metabolism highlight males' lower insulin sensitivity and less effective glucose utilization compared to females due to androgenic effects. Testosterone's intricate role extends to potential benefits in glycemic control, fat mass reduction, and muscle strength increase in men with diabetes. However, cautious consideration of testosterone therapy is crucial, especially in the presence of underlying health conditions, warranting further research for clear guidelines in managing hyperglycemia.

Future clinical prospects of C-peptide testing in the early diagnosis of gestational diabetes.

Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy. It is one of the most common metabolic disorders among expectant mothers, with potential serious short- and long-term complications for both maternal and offspring health. C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin. It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin. Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis. Inadequate compensation by islet beta-cells results in hyperglycemia. The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis. Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes. Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.

Glucose Homeostasis, Diabetes Mellitus, and Gender-Affirming Treatment.

The transgender (trans) population includes individuals with gender identities more fittingly aligned with the opposite sex or with an alternative that transcends the classical dipole of male/female. Hormonal treatment in transgender individuals aims to suppress the secretion of endogenous sex steroids and replace them with the steroids of the desired gender. The mainstay of gender-affirming treatment in transgender males is testosterone, whereas for transgender females it is estrogen, usually combined with an anti-androgen or a gonadotropin-releasing hormone agonist if testes are present. Testosterone and estrogen are involved in carbohydrate metabolism via direct effects on skeletal muscle, liver, adipose tissue, and immune cells and indirectly through changes in body fat mass and distribution. The effect of transgender treatment on glucose tolerance is not clear. The provided conflicting results demonstrate a positive, neutral, or even negative association between exogenous testosterone and insulin sensitivity in trans men. Studies show that feminizing hormonal therapy of trans women has mainly an aggravating effect on insulin sensitivity. The existing evidence is not robust and further research is needed to investigate the relationships between body fat distributions, muscle mass, and glycemia/insulin resistance in transgender people under hormonal therapy.

Melatonin's actions are not limited to sleep.

Melatonin is widely available as a supplement, usually for sleep disorders. The consumption of melatonin supplements has increased considerably in recent years. An overlooked aspect of melatonin's administration is the resulting increase in prolactin secretion, via its action on hypothalamic dopaminergic neurons. We believe that since the effect of melatonin on prolactin is tangible, the laboratory finding of hyperprolactinemia could be encountered more often, given the increase in melatonin's use. This is an issue that merits further study.

Study on the Interaction between Serum Thyrotropin and Semen Parameters in Men.

The effect of thyroid function on semen parameters has been studied in pathological conditions in small studies. With this research work, we aimed to study thyroid hormone effects on semen parameters in 130 men who were evaluated for couple subfertility. Our study was cross-sectional. We noted semen volume, sperm concentration, total sperm count, testosterone levels and thyrotropin (TSH) levels. The analysis included ordinary least squares regression (OLS-R), quantile regression (QR) and segmented line regression (SR). Using OLS-R, a weak negative correlation was found between the logTSH levels and semen volume (r = -0.16, r2 = 0.03, p = 0.05). In Q-R, each incremental unit increase in logTSH decreased the mean semen volume between -0.78 ± 0.44 and -1.33 ± 0.34 mL (40-60th response quantile) and between -1.19 ± 0.71 and -0.61 ± 0.31 mL (70-90th response quantile) (p = 0.049). With SR, a biphasic relationship of sperm concentration with TSH was noted (positive turning to negative, peaking at TSH = 1.22 µIU/mL). Thus, a weak negative association between the TSH levels and semen volume was noted, showing a trough within the usual normal range for TSH. Moreover, a biphasic relationship between the sperm concentration and TSH was also noted, peaking at approximately mid-normal TSH levels. Based on our results, TSH explained slightly less than 3% of the variation in semen volume and 7% of the sperm concentration (thus, other factors, which were not studied here, have a more important effect on it).

Alpha-Methyldopa May Attenuate Insulin Demand in Women with Gestational Diabetes Treated with Betamethasone.

Gestational diabetes mellitus (GDM) is associated with hypertensive disorders in pregnancy. Alpha-methyl-DOPA (αMD) is a commonly used medication for hypertension in pregnant women. This medication may be associated with alteration in insulin resistance and glucose homeostasis. The aim of the present study was to investigate in 152 pregnant women whether the demands of exogenous insulin in glucocorticoid-treated women during pregnancy are different between those with GDM and hypertension treated with αMD and those without hypertension. In the group of women with GDM under insulin treatment, who received αMD for hypertension, the increase in insulin needs was relatively lower by at least 30% of the pre-admission insulin dose compared to all of the remaining women not receiving αMD in the same group (9 women vs. 50 women, p = 0.035). Our work raises the hypothesis that αMD can favorably modulate insulin sensitivity in the third trimester of pregnancy in previously insulin-treated women with gestational diabetes who receive glucocorticoids.

Insulin requirements during lactation in women with diabetes mellitus type 1 in comparison with pre-pregnancy levels: A 10-year retrospective study.

The metabolic profile variability of women with diabetes mellitus type 1 (DM1) during breastfeeding, leads to a reassessment in managing glycemia, mainly to prevent hypoglycemia. In this retrospective study we assessed insulin needs, vis-à-vis breastfeeding in DM1. A 10.7% reduction of daily insulin dosage, compared to pre-pregnancy insulin needs, was noted in women who breastfed exclusively versus 10.8% in those who supplemented breastfeeding (p = NS). Women who experienced hypoglycemic episodes, tended (but not significantly) to be younger (p = 0.10), with longer duration of DM1 and more weight gain in pregnancy. Exclusive breastfeeding was associated with younger age (p = 0.04), regardless of hypoglycemia (p = 0.25).

Cystic Fibrosis-Related Diabetes and Subclinical Hypothyroidism in Pregnancy.

Pregnancy in women with cystic fibrosis-related diabetes (CFRD) is rare and requires intensive monitoring and individualized treatment due to the pathophysiologic parameters of the disease in relation to insulin therapy and special nutritional needs. We present the case of a 33-year-old primigravida woman with CFRD (ΔF508 homozygote, with mild pulmonary involvement) on insulin therapy and treatment for exocrine pancreatic insufficiency, who developed subclinical hypothyroidism during gestation. Due to the complexity of the disease, major clinical challenges were glycemic variance, hypoglycemic episodes, and difficulty in weight gaining. In addition, the presence of malabsorption in the intestinal mucosa was an important aspect of difficulty in the treatment of subclinical hypothyroidism. Thus, the flexible approach in the timing of basal insulin administration, combined with the individualized medical nutrition therapy, and along with the progressive increase in levothyroxine dosage, all were proven to be key components in the effective management of our patient.

Postpartum Follow-Up of Women Who Developed Subclinical Hypothyroidism during Pregnancy.

There is inconsistency in the literature regarding the management of women diagnosed with subclinical hypothyroidism (SCH) during pregnancy in the postpartum period. The purpose of our study was to assess the need for continuation of levothyroxine (LT4) treatment after delivery. We conducted a retrospective cohort study of 114 women with new-onset SCH during pregnancy and at 1-year follow-up postpartum. Criteria for continuation of LT4 after delivery were breastfeeding, thyrotropin (TSH) levels at diagnosis >5 mIU/L, positive antithyroid antibodies and LT4 dose before delivery >50 µg/day. On treatment initiation, mean TSH ± SD was 5.24 ± 2.55 mIU/L. One year after delivery, most patients (86/114) were still on LT4. This was related to TSH levels at the initiation of treatment in gestation (p = 0.004) and inversely related to primiparity (p = 0.019). In the group of patients who stopped LT4 postpartum, treatment was reinstated in 11 out of 39 (28.2%) due to SCH relapse (mean TSH ± SD = 9.09 ± 5.81 mIU/L). Most women in our study continued treatment after delivery, and a considerable number of women who had discontinued LT4 restarted treatment postpartum. These results stress the need to reassess thyroid function at 6 to 12 months postpartum.

Atmospheric Pollution and Thyroid Function of Pregnant Women in Athens, Greece: A Pilot Study.

Exposure to air pollution and, in particular, to nitrogen dioxide (NO2) or particulate pollutants less than 2.5 µm (PM2.5) or 10 µm (PM10) in diameter has been linked to thyroid (dys)function in pregnant women. We hypothesized that there may be a dose-effect relationship between air pollutants and thyroid function parameters. We retrospectively evaluated thyrotropin (TSH) in 293 women, NO2, PM2.5 and PM10 levels in Athens. All the women were diagnosed with hypothyroidism for the first time during their pregnancy. Exposure to air pollution for each woman was considered according to her place of residence. Statistical analysis of age, pregnancy weight change, and air pollutants versus TSH was performed with ordinary least squares regression (OLS-R) and quantile regression (Q-R). A positive correlation for logTSH and PM2.5(r = +0.13, p = 0.02) was found, using OLS-R. Further analysis with Q-R showed that each incremental unit increase (for the 10th to the 90th response quantile) in PM2.5 increased logTSH(±SE) between +0.029 (0.001) to +0.025 (0.001) mIU/L (p < 0.01). The other parameters and pollutants (PM10 and NO2) had no significant effect on TSH. Our results indeed show a dose-response relationship between PM2.5 and TSH. The mechanisms involved in the pathophysiological effects of atmospheric pollutants, in particular PM2.5, are being investigated.

Glycemia after Betamethasone in Pregnant Women without Diabetes-Impact of Marginal Values in the 75-g OGTT.

Betamethasone (BM) administration in pregnancy has been shown to reduce the incidence and severity of neonatal respiratory distress syndrome. Its known diabetogenic impact, combined with placental insulin resistance, leads to a transient increase in glycemia. However, its effect on glucose homeostasis in pregnancy has not been adequately investigated. We closely monitored and assessed the glycemic profile of 83 pregnant women, with normal glucose metabolism, who were given BM during their hospitalization due to threatened premature labor. A significant change in the glycemic profile in most patients was noted, lasting 1.34 ± 1.05 days. Sixty-six of eighty-three women were eventually treated with insulin to maintain glycemia within acceptable limits. The mean ± SD insulin dosage was 12.25 ± 11.28 units/day. The need for insulin therapy was associated with higher BM doses and the presence of marginal values in the 75-g oral glucose tolerance test (OGTT) at 60 min. Our study demonstrates, following BM administration, the need for increased awareness and individualized monitoring/treatment of pregnant women with normal-yet marginal-values in the 75-g OGTT.

Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.

UNLABELLED: AIM. To elucidate the dynamics of FSH, LH, prolactin (PRL), TSH and insulin secretion in women with polycystic ovarian syndrome (PCOS) treated with metformin (MET). PATIENTS AND METHODS: In a prospective, controlled and randomised trial, 32 women with PCOS and 32 with normal cycle were recruited to receive MET (850 mg b.i.d.) or placebo (n: 16 for each subgroup) for an average of 40 days. Pituitary function and insulin secretion were assessed before and after intervention by GnRH-TRH tests and oral glucose tolerance test induced insulin response. RESULTS: Basal and area under the response curve (AURC) LH values were higher in PCOS than in normal controls before MET and declined following treatment in the former group (P < 0.05). Ovulatory PCOS responders had lower basal LH, AURC(LH) and AURC(PRL) values during MET than anovulatory cases (P < 0.05 for all) and AURCins was lower in ovulatory than anovulatory PCOS before and on MET (P < 0.02-P < 0.05), with a rise of QUICKY index in the former group during MET treatment (P < 0.05). FSH and TSH were similar. CONCLUSIONS: MET administration lowered LH activity in all PCOS women and in ovulatory responders and also compromised PRL stimulated secretion in the latter cases. These findings were indicative of an effect of MET on pituitary activity.

Body mass index vis-à-vis total sperm count in attendees of a single andrology clinic.

In this large series of 349 unselected men, no significant relationship between body mass index and total sperm count was found. Thus, the association of body mass index and sperm count reported in some studies was not confirmed.

Association of carotene rich diet with hypogonadism in a male athlete.

AIM: To report on a unique case of hypogonadism associated with excessive carotene intake in a young male athlete. CASE REPORT: A 20-year-old patient presented with a gradual decline in muscular and physical activity, sexual interest and erectile ability associated with a high in carotene and low in animal fat diet of his own design a year prior to the clinical manifestations. Clinically, he presented with very overt signs of carotene excess: his palms and soles were yellow. Moreover, 2 weeks after normalization of his diet, carotene B levels were at the upper end of the normal range. METHODS: Repeated stimulation tests of hypothalamic, pituitary and testicular function were performed before and at 3, 6 and 12 months after the introduction of a balanced diet. RESULTS: Very low basal and stimulated values for gonadotropins and gonadal steroids were found at the initial evaluation with a progressive recovery shown after months of a balanced diet and carotene B restoration. Complete androgen secretion and sexual response recovery were observed only after 9-12 months from diagnosis. CONCLUSION: This is the first report associating excessive carotene intake with a hypothalamic form of hypogonadism in a young man.