Novel Indices of Glucose Homeostasis Derived from Principal Component Analysis: Application for Metabolic Assessment in Pregnancy.

AIMS: This study is aimed at assessing the association of previously developed indices of glucose homeostasis derived from principal component analysis (PCA) with parameters of insulin action, secretion, and beta cell function during pregnancy. METHODS: In this prospective longitudinal study, an oral glucose tolerance test was performed in sixty-seven pregnant women at two prepartum (12+0 to 22+6 and 24+0 to 28+6) and one postpartum (2 to 11 months) visits. Three principal component scores (PCS) were calculated based on measurements of glucose, insulin, C-peptide, age, and BMI to assess their association with fasting and dynamic indices of insulin action, secretion, and ß-cell function. RESULTS: PCS1 was positively associated with fasting and dynamic parameters of insulin sensitivity (Matsuda index: r = 0.93, p < 0.001), whereas a strong negative association was observed for early, late, and total insulin response. PCS2 was associated with higher mean glucose but negatively related to parameters of insulin secretion. PCS3 was significantly associated with fasting indices of insulin sensitivity. PCS1 to 3 assessed at early pregnancy were also associated with development of GDM, whereby random forest analysis revealed the highest variable importance for PCS1. PCS1 to 3 were significantly related to the oral disposition index explaining 49.0% of its variance. CONCLUSIONS: PCS1 to 3 behaved similarly as compared to previous observations in nonpregnant women and were furthermore associated with the development of GDM. These findings support our hypothesis that PCS1 to 3 could be used as novel indices of glucose disposal during pregnancy.

Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia.

BACKGROUND: Depending on CYP21A2 genotype, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to biochemical alterations (including hyperandrogenism, hypocortisolism, and hypoaldosteronism) and a wide spectrum of phenotypic disease manifestation. The latter include life-threatening salt-wasting crises, prenatal virilization of genitalia in women (classic CAH [C-CAH]) as well as milder forms of the disease exclusively presenting with hirsutism, acne or reduced fertility (nonclassic CAH [NC-CAH]), and could influence sexual function and identity. AIM: The present study evaluated sexual function, gender identification, and partner preference in women with C-CAH and NC-CAH. METHODS: In a cross-sectional cohort analysis, 35 female patients with CAH were divided into 2 groups: C-CAH (salt-wasting/simple virilizing; n = 17) and NC-CAH (n = 18) according to genotype and phenotype. Sexual function and sexual distress were assessed using established questionnaires, including the Female Sexual Function Index. Phenotype (defined by signs of hyperandrogenism) was assessed clinically (Ferriman-Gallwey score) and with the ovulatory function index. CYP21A2 genotype was determined by Sanger sequencing and multiplex ligation-dependent probe amplification. Sexual function was also separately analyzed in the context of clinical signs of androgenization in women with (n = 13) and without acne (n = 22). OUTCOMES: The study outcomes were sexual function and sexual distress in relation to genotype, clinical signs of androgenization, and biochemical parameters. RESULTS: Women with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress, as well as biochemical evidence of hyperandrogenism (higher dehydroepiandrosterone sulfate and lower SHBG) and a trend toward more clinical signs of hyperandrogenism (hirsutism). Indicators of in utero and childhood androgen excess as well as the presence of acne in all patients were related to lower sexual function and higher sexual distress. Clinical signs of hyperandrogenism correlated well with cardiovascular and metabolic risk factors. CLINICAL TRANSLATION: Women with NC-CAH and women with clinical signs of hyperandrogenism demonstrated higher distress compared to women with C-CAH and women without clinical signs of hyperandrogenism, respectively, regarding different aspects of sexual function. CONCLUSIONS: These data underline the importance of early diagnosis and therapy initiation, especially in patients with NC-CAH. Schernthaner-Reiter MH, Baumgartner-Parzer S, Egarter HC, et al. Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia. J Sex Med 2019;16:1529-1540.