The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor.

Blood pressure (BP) regulation is a complex process involving various hormones, including aldosterone and its mineralocorticoid receptor. Mineralocorticoid receptor is expressed in several tissues, including the kidney, and plays a crucial role in regulating BP by controlling the sodium and water balance. During different stages of life, hormonal changes can affect mineralocorticoid receptor activity and aldosterone levels, leading to changes in BP. Increasing evidence suggests that sex steroids modulate aldosterone levels. Estrogens, particularly estradiol, mediate aldosterone biosynthesis by activating classical estrogen receptors and the G protein-coupled receptor. Progesterone acts as an anti-mineralocorticoid by inhibiting the binding of aldosterone to the mineralocorticoid receptor. Moreover, progesterone inhibits aldosterone synthase enzymes. The effect of testosterone on aldosterone synthesis is still a subject of debate. However, certain studies show that testosterone downregulates the mRNA levels of aldosterone synthase, leading to decreased plasma aldosterone levels.

Substituting serum anti-Müllerian hormone for polycystic ovary morphology increases the number of women diagnosed with polycystic ovary syndrome: a community-based cross-sectional study.

STUDY QUESTION: Can serum anti-Müllerian hormone (AMH) replace polycystic ovary morphology (PCOM) determined by ultrasound as a diagnostic component of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Despite good correlations between serum AMH and PCOM, the use of a high serum AMH as a proxy for PCOM resulted in the reclassification of PCOS in 5% of study participants, with the main effect being more women identified, although some women previously classified as having PCOS were no longer classified as such. WHAT IS KNOWN ALREADY: AMH has been proposed as an alternative to PCOM as a diagnostic component of PCOS. Previous studies are limited by poorly defining PCOS, use of infertile women as comparators, measurement of hormones by immunoassay that lack precision in the female range, low-resolution ovarian ultrasound and inconsistent handling and storage of serum samples. STUDY DESIGN, SIZE, DURATION: This is an Australian cross-sectional study of 163 non-healthcare-seeking women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH was measured by both the Ansh picoAMH assay and the Beckman Coulter Access 2 (BA2) assay, in parallel with androgens measured by liquid chromatography-tandem mass spectrometry, in blood samples of women, not pregnant, breast feeding or using systemic steroids, who also underwent high-resolution ovarian ultrasound. PCOS was determined by the Rotterdam criteria with PCOM defined by the Androgen Excess-PCOS Taskforce recommendation of ≥25 follicles in at least one ovary. Cut-off serum concentrations that best identified women as having PCOM were identified by receiver operator characteristic (ROC) curves. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 163 women, mean (SD) age 32.5 (5.5) years, who provided a blood sample and had both ovaries visualized on ultrasound were included in the analysis. Women with isolated PCOM had higher median (range) Ansh AMH and BA2 AMH concentrations than those with no PCOS characteristics [56.9 pmol/l (34.6, 104.2) versus 18.7 (3.2, 50.9), P = 0.002 and 38.5 pmol/l (22.2, 100.2) versus 16.7 (3.5, 38.9), P = 0.002, respectively]. An AMH ≥ 44.0 pmol/l, suggested by the ROC curve, identified 80.6% of women with PCOM, falsely identified 15.2% of women without PCOM as having PCOS and had a positive predictive value of 55.6%. The negative predictive value was 94.9%. An AMH BA2 assay cut-off of ≥33.2 pmol/l provided a sensitivity of 80.6%, a specificity of 79.5% and a positive predictive value for PCOM of 48.1%. The negative predictive value was 94.6% for PCOM. When serum AMH was used in the place of PCOM as a diagnostic criterion for PCOS, the Ansh assay resulted in an additional seven women classified as having PCOS and no longer classified one woman as having PCOS. For the BA2 assay, eight additional and two fewer women were classified as having PCOS. Overall, both assays resulted in six more women being classified as having PCOS. LIMITATIONS, REASONS FOR CAUTION: Women with functional hypogonadotrophic hypogonadism were not excluded and may have been misclassified as having an oligo-amenorrhoea-PCOM phenotype. As study participants were predominantly Caucasian/White, our findings cannot be generalized to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Although serum AMH reflects the number of developing ovarian follicles, the absolute values vary between assays and specific reference ranges for individual assays are required. Irrespective of the assay used, replacing PCOM with serum AMH to diagnose PCOS in a community-based sample altered the number of women classified as having or not having PCOS. Consequently, although overall the risk of women being identified as having PCOS would be increased, some women would no longer be classified as having this condition. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Norman Beischer Research Foundation and the Grollo-Ruzzene Foundation. S.R.D. is an NHMRC Senior Principal Research Fellow (Grant No. 1135843). S.R.D. reports unrelated support that includes grants from the NHMRC Australia, personal fees for educational activities from Besins Healthcare, Abbott Chile, BioFemme and Pfizer Australia, personal Advisory Board/consultancy fees from Theramex, Abbott Laboratories, Astellas, Mayne Pharmaceuticals, Roche Diagnostics, Lawley Pharmaceuticals and Que Oncology and has received institutional grant funding from Que Oncology and Ovoca research. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Estrone Is a Strong Predictor of Circulating Estradiol in Women Age 70 Years and Older.

IMPORTANCE: After menopause, estradiol (E2) is predominately an intracrine hormone circulating in very low serum concentrations. OBJECTIVE: The objective of this work is to examine determinants of E2 concentrations in women beyond age 70 years. DESIGN AND SETTING: A cross-sectional, community-based study was conducted. PARTICIPANTS: A total of 5325 women participated, with a mean age of 75.1 years (±â€…4.2 years) and not using any sex steroid, antiandrogen/estrogen, glucocorticoid, or antiglycemic therapy. MAIN OUTCOME MEASURES: Sex steroids were measured by liquid chromatography-tandem mass spectrometry. Values below the limit of detection (LOD; E2 11 pmol/L [3 pg/mL] were assigned a value of LOD/√2 to estimate total E2. RESULTS: E2 and estrone (E1) were below the LOD in 66.1% and 0.9% of women, respectively. The median (interdecile ranges) for E1 and detectable E2 were 181.2 pmol/L (range, 88.7-347.6 pmol/L) and 22.0 pmol/L (range, 11.0-58.7 pmol/L). Women with undetectable E2 vs detectable E2 were older (median age 74.1 years vs 73.8, P = .02), leaner (median body mass index [BMI] 26.8 kg/m2 vs 28.5, P < .001), and had lower E1, testosterone and DHEA concentrations (P < .001). A linear regression model, including age, BMI, E1, and testosterone, explained 20.9% of the variation in total E2, but explained only an additional 1.2% of variation over E1 alone. E1 and testosterone made significant contributions (r2 = 0.162, P < .001) in a model for the subset of women with detectable E2. CONCLUSIONS: Our findings support E1 as a principal circulating estrogen and demonstrate a robust association between E1 and E2 concentrations in postmenopausal women. Taken together with prior evidence for associations between E1 and health outcomes, E1 should be included in studies examining associations between estrogen levels and health outcomes in postmenopausal women.