Establishing Normative Values to Determine the Prevalence of Biochemical Hyperandrogenism in Premenopausal Women of Different Ethnicities from Eastern Siberia

Abstract

Androgen assessment is a key element for diagnosing polycystic ovary syndrome (PCOS), and defining a “normal” level of circulating androgens is critical for epidemiological studies. We determined the upper normal limits (UNLs) for androgens in a population-based group of premenopausal “healthy control” women, overall and by ethnicity (Caucasian and Asian), in the cross-sectional Eastern Siberia PCOS Epidemiology and Phenotype (ESPEP) Study (СlinicalTrials.gov ID: NCT05194384) conducted in 2016–2019. Overall, we identified a “healthy control” group consisting of 143 healthy premenopausal women without menstrual dysfunction, hirsutism, polycystic ovaries, or medical disorders. We analyzed serum total testosterone (TT) by using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and DHEAS, sex-hormone-binding globulin (SHBG), TSH, prolactin, and 17-hydroxyprogesterone (17OHP) were assessed with an enzyme-linked immunosorbent assay (ELISA). The UNLs for the entire population for the TT, free androgen index (FAI), and DHEAS were determined as the 98th percentiles in healthy controls as follows: 67.3 (95% confidence interval (CI): 48.1, 76.5) ng/dl, 5.4 (3.5,14.0), and 355 (289, 371) μg/dl, respectively. The study results demonstrated that the UNLs for TT and FAI varied by ethnicity, whereas the DHEAS UNLs were comparable in the ethnicities studied.

Ovarian Morphology in Non-Hirsute, Normo-Androgenic, Eumenorrheic Premenopausal Women from a Multi-Ethnic Unselected Siberian Population

“…At the same time, prolactin levels were significantly higher (within normative ranges) in Asians as compared to Caucasian women. When studying the impact of ethnicity on androgens, we found that TT, DHAS, and FAI values in the study population were significantly lower in Asians than in Caucasian women, but they were in the normative ranges for the multi-ethnic Siberian population [16]. At the same time, Asians showed lower levels of SHBG (Table S1).…”

“…Study design and population. Study subjects were recruited during the cross-sectional institution-based prospective Eastern Siberia PCOS epidemiology and phenotype (ESPEP) study (ClinicalTrials.gov ID: NCT05194384), conducted in two major areas of Eastern Siberia (the Irkutsk region and the Buryat Republic, Russian Federation) from March 2016 to December 2019, as previously described [15,16]. In brief, a total population of 1490 premenopausal women underwent a mandatory annual employment health assessment.…”

“…Of these, all women aged 18-44 years who were found to be completely healthy constituted the study population (Figure 1). The inclusion criteria for the current study population included a history of regular, predictable menstrual cycles of 21-35 days in length and no clinical signs of HA and/or elevated testosterone and/or DHAS levels and/or FAI [16]. Women with a BMI < 18 or ≥30 kg/m 2 , premature ovarian failure (based on history or due to elevated FSH), treated and untreated hyperprolactinemia (based on history or increased prolactin level > 727 mIU/mL), untreated thyroid disorder (based on history or TSH level > 4 mIU/mL), and 21-hydroxylase deficient non-classical adrenal hyperplasia (based on increased 17-hydroxyprogesterone (17-OHP) > 7.0 nmol/L), were excluded.…”

“…Women with a BMI < 18 or ≥30 kg/m 2 , premature ovarian failure (based on history or due to elevated FSH), treated and untreated hyperprolactinemia (based on history or increased prolactin level > 727 mIU/mL), untreated thyroid disorder (based on history or TSH level > 4 mIU/mL), and 21-hydroxylase deficient non-classical adrenal hyperplasia (based on increased 17-hydroxyprogesterone (17-OHP) > 7.0 nmol/L), were excluded. The main characteristics of the study population, including their socio-demography, menstrual and and/or FAI [16]. Women with a BMI < 18 or ≥30 kg/m 2 , premature ovarian failure (based on history or due to elevated FSH), treated and untreated hyperprolactinemia (based on history or increased prolactin level > 727 mIU/mL), untreated thyroid disorder (based on history or TSH level > 4 mIU/mL), and 21-hydroxylase deficient non-classical adrenal hyperplasia (based on increased 17-hydroxyprogesterone (17-OHP) > 7.0 nmol/L), were excluded.…”