Free Androgen Index Research Articles

The associations between exposure to mixed environmental endocrine disruptors and sex steroid hormones in men: a comparison of different statistical models

In recent years, worldwide fertility rates have continued to decrease. Humans are frequently exposed to a combination of environmental endocrine disruptors, which can cause male reproductive disorders. The study employed three distinct analytical models to examine the correlation between exposure to a combination of 25 chemicals and sex steroid hormone levels in adult males. This involved evaluating 12 chemicals and their metabolites from personal care and consumer products, as well as 13 metabolites linked to phthalates and plasticisers. The study analysed 25 chemicals and 3 measured sex steroid hormone outcomes, as well as two calculated hormonal outcomes (free androgen index, TT/E2 ratio) in 1262 adult men who participated in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 in the United States. The study employed several statistical methods to estimate the relationships between single chemicals or chemical blends and sex hormones. These methods included linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine (BKMR) regression. The results of the linear regression analysis indicate that chemical exposure has a negative correlation with E2, TT, and FAI, and a positive correlation with SHBG and TT/E2. The mixture effect analyses using the WQS and BKMR models further confirmed that BP3, MECPP, and MECOP were the most highly weighted chemical mixtures. The analyses also suggested that there were differences in the effects of different concentrations of EDCs on sex steroid hormones. Exposure to environmental endocrine-disrupting chemicals (EDCs) has been found to have a negative correlation with estradiol and total testosterone, as well as FAI. Conversely, this exposure has been found to have a positive correlation with sex hormone binding globulin and the TT/E2 ratio. The study also revealed differences in the effects of different concentrations of EDCs.

Metabolic Syndrome Severity Score in Subjects with and without Poly Cystic Ovarian Syndrome

Objective: To compare polycystic ovarian syndrome and their defining criteria with metabolic syndrome severity score among females with and without polycystic ovarian syndrome. Study Design: Comparative cross-sectional study. Place and Duration of Study: Naval Hospital Islamabad, from Jan 2018 to Dec 2021. Methodology: We evaluated 293 female subjects for Poly Cystic Ovarian Syndrome after several exclusions who presented with an initial complaint of disturbances in menstrual cycles. These subjects underwent clinical examination including blood pressure and anthropometric indices and measurements of modified Ferriman Gallway score. Biochemical measurements included fasting plasma glucose, HDL cholesterol, triglycerides and insulin measurement. These parameters were measured for various components included in defining the Poly Cystic Ovarian Syndrome as per Rotterdam criteria and Metabolic Syndrome Severity Score equation to compare metabolic syndrome severity and insulin resistance among subjects with Poly Cystic Ovarian Syndrome and without Poly Cystic Ovarian Syndrome. Results: Mean age among participants were 29.46±6.74 years. Disturbances in menstrual cycle reporting oligo/anovulation was reported by (181/293) 61.8% in comparison to (112/293) 38.2%. Hirsutism (modified Ferriman Gallway score>8) was present in (142/293) 48.5%. Radiological findings pointing towards Poly Cystic Ovarian Syndrome diagnosis were found in (72/293) 24.6%. Metabolic Syndrome Severity Score showed higher correlation with age, and insulin resistance in contrast to hirsutism and free androgen indices. Hirsutism was higher among oligo/anovulation females than participants without menstrual complaints (14.17+8.99 vs. 11.16+7.88, p=0.004). Similarly, bioc Conclusion: Metabolic Syndrome Severity Score equation does not associate with Poly Cystic Ovarian Syndrome criteria as defined by Rotterdam. Insulin resi

Altered bile acids profile is a risk factor for hyperandrogenism in lean women with PCOS: a case control study

The levels of fasting-state serum bile acids (BAs) in individuals with polycystic ovary syndrome (PCOS) differ from those of control subjects. However, there is a lack of research on the BAs profile in lean women with PCOS and whether these changes are linked to the host metabolism. Therefore, our objective was to investigate the synthesis and metabolism of serum BAs in lean women with PCOS and assess the correlation between BAs and clinical characteristics. This study employed a cross-sectional design of lean women with PCOS (n = 240) in comparison to a control group (n = 80) consisting of healthy lean women. The findings revealed significant increases in the levels of non-12-OH BAs and chenodeoxycholic acid (CDCA)% (both P < 0.05) in lean women with PCOS. Additionally, a positive correlation was observed between CDCA% and total testosterone (T) (r = 0.130, P = 0.044) and free androgen index (FAI) (r = 0.153, P = 0.019). Furthermore, a decreased ratio of cholic acid/chenodeoxycholic acid (CA/CDCA) (P < 0.001) was observed in lean women with PCOS, suggesting the depletion or downregulation of CYP8B1. Receiver operating characteristic curve analysis indicated that the combination of CDCA/CA and DHEAS could potentially be used as a characteristic factor for PCOS in lean women. It is possible that enzymatic modifications in the liver could play a role in regulating hyperandrogenism in this specific subgroup of lean women with PCOS.

The Relation of Insulin Resistance With Free Androgen Index and Endothelial Dysfunction Marker YKL-40 and Its Effect on Male Infertility: A Prospective Study

The Relation of Insulin Resistance With Free Androgen Index and Endothelial Dysfunction Marker YKL-40 and Its Effect on Male Infertility: A Prospective Study

Metabolic Syndrome in Reproductive Age Women of Various Ethnic Groups. Neuroendocrine Status and Lipid Peroxidation System.

We analyzed the state of neuroendocrine regulation and LPO-antioxidant defense systems in reproductive age women with metabolic syndrome (MetS), representatives of the Russian and Buryat ethnic groups. Compared to the corresponding control groups, women from the Russian ethnic group with MetS had elevated levels of thyroid-stimulating hormone and free androgen index (FAI) and reduced levels of sex hormone-binding globulin, while women from the Buryat ethnic group had increased levels of prolactin and FAI. Changes in the LPO system in women of the Russian ethnic group with MetS consisted in an increase in the levels of substrates with double bonds, TBA-reactive substances, and fat-soluble vitamins. Buryat women with MetS had a higher content of primary oxidation products and reduced levels of glutathione. The results of the study indicate a hyperandrogenic shift in the neuroendocrine regulation system, as well as compensatory influences from different parts of the antioxidant defense system in women of reproductive age with MetS, depending on their ethnicity. These findings indicate the need for assessing and monitoring the levels of these metabolites in women with MetS, considering their ethnicity.

Associations of Co-Exposure to Polycyclic Aromatic Hydrocarbons and Heavy Metals with Sex Steroid Hormones among Children Aged 6–19 Years

Plain Language SummaryPolycyclic aromatic hydrocarbons (PAHs) and HMs are two classic groups of environmental endocrine-disrupting chemicals (EDCs). PAHs usually coexist with HMs and they may have a combined effect in affecting sex hormone levels in children. Sex steroid hormones have an important role in children’s growth and development which affects growth rate, central nervous system function, normal skeletal mineralization, and reproductive health. This study investigated the correlations between co-exposure to PAHs and HMs and levels of sex steroid hormones in children. Weighted multivariate linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze the associations between co-exposure to PAHs and HMs and sex steroid hormone levels. We found that co-exposure to PAHs and HMs was associated with the levels of estradiol (E2), the testosterone (TT)/E2 ratio, free androgen index (FAI), and sex hormone-binding globulin (SHBG). Our analysis reveals that co-exposure to PAHs and HMs is hazardous to the reproductive health of children, and further mechanism and prospective studies are needed to provide additional substantial evidence.

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

8102 Hyperandrogenism and its Influence on Emotional and Social Development in Adolescent Daughters of Women with Polycystic Ovary Syndrome

Abstract Disclosure: J.P. del Rio: None. R. Gonzalo: None. M. Maliqueo: None. B. Echiburu: None. A. Ladron de Guevara: None. P. Gaspar: None. M. Alejandro: None. N.R. Crisosto: None. Introduction: Polycystic Ovarian Syndrome (PCOS) is the most prevalent endocrine disorder in adolescents. PCOS is characterized by hyperandrogenism, which can modulate brain maturation, especially in highly neuronal plasticity periods, such as intra-uterine life and adolescence. Daughters of women with PCOS (dPCOS) will probably be exposed to hyperandrogenism during these two periods. However, the effects of hyperandrogenism on psychosocial development have not yet been fully characterized. Objectives: To characterize the consequences of hyperandrogenism in the emotional status and social cognition (SC) on dPCOS. Methods/Design: Analytical cross-sectional study. dPCOS and controls between 12 to 25 years old were recruited. Participants underwent a complete clinical evaluation, serum hormone determinations (including total testosterone, SHBG, androstenedione, 17-OH-progesterone, and OGTT-I with 4 collections (0’-30’-90’-120´)) and ovarian ultrasound characterization. Emotional status and SC were estimated by measurements of affects (PANAS), strength and difficulties (SDQ), self-reported empathy (EQ/SQ and AQ), and gaze patterns measurement via Eye-Tracking (while completing an emotional recognition task). Results: 33 participants were recruited, 15 cases and 18 controls. Median age was 17 and 18 years, respectively. The dPCOS presented a larger anogenital distance (cm) (9.7 vs 7.8; p=0.014), Ferryman-Gallwey score mean (13.0 vs 2.0; p=&amp;lt;0.001) and free androgen index value (7.5 vs 4.1; p=0.004), suggesting hyperandrogenism exposure during intrauterine and adolescence periods. Regarding emotional status and SC, dPCOS exhibited a predominantly negative affective status (PANAS 8.0 vs 2.0, p=0.049) and a higher score in socio-emotional problems (SDQ 2,5 vs 1,5; p=0,047). The eye-tracking registration showed that dPCOS presented a longer time to first fixation in areas of interest (s) (0,35 vs 0,28; p=0,037), which was associated with a worse endpoint in emotional recognition (aR2=-0,920; f=19,48; Pr &amp;gt;|t|=&amp;lt;0,049). Furthermore, the 2D:4D ratio (intrauterine marker of androgen exposure) and insulin levels at 60’ were correlated with a predominance of negative affects (rho=0,51; p=0,019 and rho= -0,48; p=0,035), and 2D:4D ratio was also correlated with less prosocial behaviors (coef=-2,39; P&amp;gt;|t|=0,049). Conclusions: Clinical and hormonal markers suggest that dPCOS are exposed to hyperandrogenism during the most critical neuroplasticity periods. This exposure is associated with a predominance of negative affects, more social-emotional difficulties and worse performance on emotional recognition and prosocial behavior. Considering PCOS patient’s elevated psychiatric comorbidity, early mental health intervention becomes crucial, underscoring the necessity for in-depth study on hyperandrogenism's impacts on psychosocial development. Presentation: 6/3/2024

8102 Hyperandrogenism and its Influence on Emotional and Social Development in Adolescent Daughters of Women with Polycystic Ovary Syndrome

Abstract Disclosure: J.P. del Rio: None. R. Gonzalo: None. M. Maliqueo: None. B. Echiburu: None. A. Ladron de Guevara: None. P. Gaspar: None. M. Alejandro: None. N.R. Crisosto: None. Introduction: Polycystic Ovarian Syndrome (PCOS) is the most prevalent endocrine disorder in adolescents. PCOS is characterized by hyperandrogenism, which can modulate brain maturation, especially in highly neuronal plasticity periods, such as intra-uterine life and adolescence. Daughters of women with PCOS (dPCOS) will probably be exposed to hyperandrogenism during these two periods. However, the effects of hyperandrogenism on psychosocial development have not yet been fully characterized. Objectives: To characterize the consequences of hyperandrogenism in the emotional status and social cognition (SC) on dPCOS. Methods/Design: Analytical cross-sectional study. dPCOS and controls between 12 to 25 years old were recruited. Participants underwent a complete clinical evaluation, serum hormone determinations (including total testosterone, SHBG, androstenedione, 17-OH-progesterone, and OGTT-I with 4 collections (0’-30’-90’-120´)) and ovarian ultrasound characterization. Emotional status and SC were estimated by measurements of affects (PANAS), strength and difficulties (SDQ), self-reported empathy (EQ/SQ and AQ), and gaze patterns measurement via Eye-Tracking (while completing an emotional recognition task). Results: 33 participants were recruited, 15 cases and 18 controls. Median age was 17 and 18 years, respectively. The dPCOS presented a larger anogenital distance (cm) (9.7 vs 7.8; p=0.014), Ferryman-Gallwey score mean (13.0 vs 2.0; p=&amp;lt;0.001) and free androgen index value (7.5 vs 4.1; p=0.004), suggesting hyperandrogenism exposure during intrauterine and adolescence periods. Regarding emotional status and SC, dPCOS exhibited a predominantly negative affective status (PANAS 8.0 vs 2.0, p=0.049) and a higher score in socio-emotional problems (SDQ 2,5 vs 1,5; p=0,047). The eye-tracking registration showed that dPCOS presented a longer time to first fixation in areas of interest (s) (0,35 vs 0,28; p=0,037), which was associated with a worse endpoint in emotional recognition (aR2=-0,920; f=19,48; Pr &amp;gt;|t|=&amp;lt;0,049). Furthermore, the 2D:4D ratio (intrauterine marker of androgen exposure) and insulin levels at 60’ were correlated with a predominance of negative affects (rho=0,51; p=0,019 and rho= -0,48; p=0,035), and 2D:4D ratio was also correlated with less prosocial behaviors (coef=-2,39; P&amp;gt;|t|=0,049). Conclusions: Clinical and hormonal markers suggest that dPCOS are exposed to hyperandrogenism during the most critical neuroplasticity periods. This exposure is associated with a predominance of negative affects, more social-emotional difficulties and worse performance on emotional recognition and prosocial behavior. Considering PCOS patient’s elevated psychiatric comorbidity, early mental health intervention becomes crucial, underscoring the necessity for in-depth study on hyperandrogenism's impacts on psychosocial development. Presentation: 6/3/2024

8354 OVARIAN HYPERTHECOSIS: AN UNCOMMON CAUSE OF HYPERANDROGENISM IN A POSTMENOPAUSAL WOMAN

Abstract Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None. Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV &amp;lt;6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool. Presentation: 6/2/2024

8354 Ovarian Hyperthecosis: an Uncommon Cause of Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None. Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV &amp;lt;6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool. Presentation: 6/2/2024

Association of Hyperandrogenaemia With Hypertension and Cardiovascular Events in Pre-menopausal Women- A Prospective Population-Based Cohort Study.

The present study aimed to clarify the conflicting association of premenopausal hyperandrogenaemia (HA) with the development of hypertension and CVDs in women. A population-based cohort study including 5889 women. The association of serum testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) at age 31 with blood pressure (BP) and hypertension (BP ≥140/90 mmHg and/or use of antihypertensive medication) at ages 31 and 46 and with CVDs (angina pectoris [AP] and/or acute myocardial infarction [AMI] n=74, transitory cerebral ischemia [TIA] and/or stroke n=150) and combined CVD events (AP, AMI, stroke, heart failure, or CVD mortality n=160) by age 53 was investigated. T and FAI were positively associated with systolic and diastolic BP at ages 31 and 46 in the multivariable model. Compared to their lowest quartile, the highest quartiles of T and FAI were positively associated with hypertension at age 31 in the multivariable model. During the 22-year follow-up, FAI was positively associated with increased risk of AP/AMI (hazard ratio [HR]:2.02, 95%CI:1.06-3.85) and overall CVD events or mortality (HR:1.54, 95%CI:1.02-2.33) in the unadjusted models. However, the significance disappeared after adjusting for BMI. Women with HA at premenopausal age had an elevated risk of hypertension, and together with BMI, increased risk of CVD events and CVD mortality during the 22-year follow-up. However, because of several study limitations regarding ethnicity and BMI characteristics, a longer follow-up of this cohort and future studies in ethnically diverse populations are needed to verify the results.

Hyperandrogenism and anthropometric parameters in women with polycystic ovary syndrome

ObjectiveOne of the main features of polycystic ovary syndrome (PCOS) is increased adipose tissue, which can result in hormonal disturbances. In the present study, we aimed to investigate which indicator of obesity could better associate with hormonal disturbances in PCOS women.MethodsIn this cross-sectional analysis, women with PCOS were included according to the Rotterdam criteria. Fasting blood samples were analyzed for biochemical, metabolic, and hormonal parameters. Anthropometric measures comprised body composition indices (assessed by bioelectric impedance analysis [BIA]), waist circumference, body mass index (BMI), and waist-to-height ratio (WHtR). Linear regression modeling was used to assess the association between anthropometric indices and hormonal imbalance, adjusted for age, mensuration status, and the homeostasis model assessment-estimated insulin resistance (HOMA-IR). Receiver operating characteristics (ROC) curves were utilized to ascertain the sensitivity, specificity, and optimal cut-off points of various anthropometric indices in identifying hyperandrogenism.ResultsA total of 129 PCOS women with a median (interquartile range [IQR]) age of 32.0 (23.0–32.0) years and a median BMI of 26.3 (23.00-29.70) kg/m2 were enrolled. In the adjusted linear regression model, BMI (β = 0.053, P < 0.001), waist circumference (β = 0.021, P = 0.001), WHtR (β = 3.325, P = 0.002), total fat mass (β = 0.021, P = 0.002), trunk fat mass (β = 0.038, P = 0.006), and leg fat mass (β = 0.045, P = 0.004) were positively associated with free androgen index (FAI). In addition, BMI (β=−0.017, P = 0.003), waist circumference (β=−0.008, P = 0.002), WHtR (β=−1.167, P = 0.004), total fat mass (β=−0.008, P=0.003), trunk fat mass (β=−0.017, P=0.001), and leg fat mass (β=−0.018, P=0.004) were negatively associated with the serum level of sex hormone binding globulin (SHBG). WHtR showed the greatest area under the curve (AUC) value (AUC = 0.676, P = 0.001) for identifying hyperandrogenism (FAI ≥ 4.97 or total testosterone ≥ 0.7 ng/mL) in PCOS women with corresponding sensitivity of 87.30% and specificity of 39.70%.ConclusionsWHtR is related to hyperandrogenism in PCOS better than other anthropometric measures.

The Impact of Vitamin D on Androgens and Anabolic Steroids among Adult Males: A Meta-Analytic Review.

Recent studies indicate that vitamin D impacts male reproductive function, with deficiency linked to infertility. This review evaluates the effect of vitamin D supplementation on male fertility, focusing on total testosterone, free testosterone, the free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone-binding globulin (SHBG), and estradiol. We systematically searched Medline, Web of Science, Cochrane Library, and Scopus from their inception until July 2024 for randomized controlled trials (RCTs) involving adult males. The primary focus of these studies was on reproductive hormone parameters, analyzed using a random-effects meta-analysis and weighted mean difference (WMD). Evidence quality was assessed using ROB2 and GRADE. Meta-regression and dose-response analyses were performed. Seventeen studies met the criteria for quantitative analysis. Vitamin D supplementation significantly increased total testosterone levels (WMD 0.38, 95% CI 0.06-0.70, n = 15, I2 = 67.03). However, it had no significant effect on other hormone parameters: free testosterone (WMD 0.00, 95% CI -0.02-0.03, n = 9, I2 = 48.12), FSH (WMD -0.02, 95% CI -0.57-0.53, n = 7, I2 = 48.72), LH (WMD -0.09, 95% CI -0.30-0.12, n = 8, I2 = 0.00), SHBG (WMD 0.73, 95% CI -1.14-2.61, n = 10, I2 = 69.05), FAI (WMD -0.92, 95% CI -2.12-0.27, n = 6, I2 = 0.00), and estradiol (WMD -0.02, 95% CI -2.95-2.92, n = 5, I2 = 20.63). This meta-analysis shows that vitamin D supplementation may increase total testosterone levels in men. However, further well-designed RCTs are needed to determine vitamin D's effects on other reproductive hormone parameters.

Gut microbiota biodiversity indices as markers of hyperandrogenemia in women of reproductive age

Introduction. Previously, it was shown that the “classic” phenotypes of polycystic ovarian syndrome (PCOS) are associated with significant decrease in gut microbiota alpha diversity as compared with healthy women.The aim of the study. To establish cut-off points for alpha diversity indices, significant in polycystic ovarian syndrome with hyperandrogenism.Material and methods. The manuscript presents a sub-study of Eastern Siberia PCOS Epidemiology and Phenotype Study, conducted in Eastern Siberia (Russia) from 2016 to 2019. All participants (175 women of reproductive age: 26 women with PCOS (according to Rotterdam criteria (2003)) and hyperandrogenemia (increased levels of total testosterone (TT) and/or free androgenindex(FAI), and/ordehydroepiandrosterone sulphate (DHEAS)), 149 – without hyperandrogenemia) were recruited during the annual employment medical assessment. Methods included a questionnaire survey, anthropometry and modified Ferriman – Gallwey score, gynecological examination, pelvic ultrasound, and blood serum tests for TT, DHEAS, sex hormone-binding globulin, FAI, prolactin, thyroid-stimulating hormone, and 17-hydroxyprogesterone. Five indices of alpha diversity (amplicon sequencing variant, Shannon index, Simpson index, Chao index, and abundance-based coverage Index) were estimated for the gut microbiota using amplicon metasequencing. Statistical analysis included ROC-analysis for development of cut-off points for the indices, associated with hyperandrogenism in women of reproductive age with PCOS. Results. According to results of ROC-analysis, the greatest sensitivity with moderate specificity, with a high area under the curve was established for the Shannon and Simpson indices with cut-off points classifying women with or without hyperandrogenemia – 5.84 and 0.97, respectively.Conclusions. The developed criteria for assessing alpha diversity using cut-off points for the most significant indices can be useful for monitoring the results of different therapeutic interventions (prebiotics, probiotics, etc.) in hyperandrogenic phenotypes of PCOS.

Effects of Intermittent Fasting on Female Reproductive Function: A Review of Animal and Human Studies.

Intermittent fasting has gained significant attention, yet a comprehensive understanding of its impact on female reproductive health is lacking. This review aims to fill this gap by examining various intermittent fasting regimens and their effects on female reproductive function, along with potential mechanisms. In healthy non-overweight/obese or pregnant animal models, alternate-day fasting (ADF) and an 8-h time-restricted feeding (TRF) window may have adverse effects on reproductive function. However, these regimens show potential to mitigate negative consequences induced by a high-fat diet (HFD) or environmental exposure. A 10-h TRF demonstrates benefits in improving fertility in both normal-weight and HFD-fed animal models. In women with overweight/obesity or polycystic ovary syndrome (PCOS), the 5:2 diet and TRF significantly reduce the free androgen index while elevating sex hormone binding globulin, promising improvements in menstrual regulation. For pregnant Muslim women, available data do not strongly indicate adverse effects of Ramadan fasting on preterm delivery, but potential downsides to maternal weight gain, neonatal birthweight, and long-term offspring health need consideration. Factors linking intermittent fasting to female reproductive health include the circadian clock, gut microbiota, metabolic regulators, and modifiable lifestyles. Drawing definitive conclusions remains challenging in this evolving area. Nonetheless, our findings underscore the potential utility of intermittent fasting regimens as a therapeutic approach for addressing menstruation irregularities and infertility in women with obesity and PCOS. On the other hand, pregnant women should remain cognizant of potential risks associated with intermittent fasting practices.

Evaluation of carotid artery elasticity and its influencing factors in non-obese PCOS patients using a technique for quantitative vascular elasticity measurement.

To evaluate the intima-media thickness (IMT) and elasticity of the carotid artery in non-obese polycystic ovary syndrome (PCOS) patients using a quantitative technique for vascular elasticity measurement and to explore the influencing factors. Sixty non-obese patients without metabolic and cardiovascular diseases who were diagnosed with PCOS in the Women and Children's Hospital of Chongqing Medical University from January to December 2022 were prospectively selected (case group), and 60 healthy volunteers matched for body mass index were included as the control group. Body weight, height, heart rate, blood pressure, and waist-to-hip ratio were recorded. Fasting blood samples were drawn from the elbow vein to measure hormone levels including total testosterone (TT), sex hormone-binding globulin (SHBG), fasting plasma glucose (FPG), fasting insulin (FINS), lipids, and homocysteine (Hcy). The insulin resistance index (HOMA-IR) and free androgen index (FAI) were calculated. Ultrasound elastography was used to measure the IMT and elastic function parameters of the right carotid artery, including vessel diameter, wall displacement, stiffness coefficient, and pulse wave velocity. Differences in various parameters between the two groups were analyzed, and correlations between the carotid stiffness coefficient and other serological indicators were assessed using Spearman correlation analysis. No significant differences in age, body mass index, heart rate, systolic blood pressure, and diastolic blood pressure were observed between the two groups (all P>0.05), while the waist-to-hip ratio (WHR) was higher in the case group than in the control group (P<0.05).The hormone level serological indicators TT and FAI were higher in the case group than in the control group, and SHBG was lower in the case group than in the control group (all P<0.05). The metabolism-related serum indicators LDL-C, HDL-C, FPG, triglycerides, and total cholesterol levels were not statistically different between the two groups (all P>0.05), and serum FINS, HOMA-IR, and Hcy levels were significantly higher in the case group than in the control group (all P<0.05).No significant difference in carotid artery diameter was observed between the case group and control group (P>0.05). The carotid artery displacement in the case group was significantly smaller than that in the control group (P<0.05), and carotid IMT, hardness coefficient, and pulse wave propagation velocity were greater in the case group than in the control group (all P<0.05). The carotid elastic stiffness coefficient was positively correlated with WHR, TT, SHBG, FAI, FINS, HOMA-IR and Hcy to varying extents and negatively correlated with SHBG. In non-obese PCOS patients with no metabolic or cardiovascular disease, the carotid stiffness coefficient was increased and correlated with indicators of hyperandrogenism, insulin resistance, and hyperhomocysteinemia.

The Concentration of Follistatin and Activin A in Serum and Selected Biochemical Parameters in Women with Polycystic Ovary Syndrome: Stratification by Tobacco Smoke Exposure, Insulin Resistance, and Overweight/Obesity.

Background/Objectives: The aim of the study was to investigate the concentrations of follistatin and activin A in the serum of women with polycystic ovary syndrome (PCOS) and to assess their relationship with selected biochemical parameters, specifically stratifying the analysis based on tobacco smoke, insulin resistance, and abnormal weight. Methods: The research was carried out within a cohort of 88 women (60 women with and 28 without PCOS). Results: We observed significant differences (p < 0.05) in follistatin concentrations between women with PCOS stratified by homeostatic model assessment for insulin resistance (HOMA-IR) values. These differences were consistent across both smoking and non-smoking subgroups with PCOS. Similar results were observed when comparing normal-weight women with PCOS to those with overweight or obesity. Additionally, activin A concentrations were significantly increased by higher body mass index (BMI) and HOMA-IR values in non-smoking women with PCOS. Moreover, we identified a negative correlation (r = -0.30; p < 0.023) between cotinine levels and Anti-Müllerian hormone. Among smoking women with PCOS, we noted decreased concentrations of sex hormone-binding globulin and high-density lipoproteins, alongside increased fasting glucose, insulin, HOMA-IR, and free androgen index values. Conclusions: Our findings suggest that activin A and follistatin concentrations are more strongly influenced by disruptions in glucose metabolism and BMI than by tobacco smoke exposure. The observed changes were more pronounced in follistatin than in activin A level.

Impact of Smoking and Obesity on the Selected Peptide Hormones and Metabolic Parameters in the Blood of Women with Polycystic Ovary Syndrome-Preliminary Study.

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.