Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens.

BACKGROUND: The endoplasmic reticulum (ER) is the central hub for protein quality control, where the protein disulfide isomerases (PDIs), encoded by at least 21 genes, play a pivotal role. These multifunctional proteins contribute to disulfide bond formation, proper folding, and protein modifications, and may act as hormone-binding proteins (e.g., steroids), influencing hormone biology. The interplay between ER proteostasis, PDIs, and epididymis-a crucial site for sperm maturation-remains largely understudied. OBJECTIVES: This study characterizes transcriptional signatures of Pdi genes in the epididymis. MATERIAL AND METHODS: Transcriptional profiles of selected Pdi genes were assessed in adult Wistar rat tissues, and epididymis under different experimental conditions (developmental stages, surgical castration, and efferent ductules ligation [EDL]). In silico bioinformatic analyses identified expression trends of this gene family in human epididymal segments. RESULTS: P4hb, Pdia3, Pdia5, Pdia6, Erp44, Erp29, and Casq1 transcripts were detected in both reproductive and non-reproductive tissues, while Casq2 exhibited higher abundance in vas deferens, prostate, and heart. Pdilt, highly expressed in testis, and Pdia2, highly expressed in heart, showed minimal mRNA levels in the epididymis. In the mesonephric duct, epididymal embryonic precursor, P4hb, Pdia3, Pdia5, Pdia6, and Erp29 mRNAs were found at gestational day (GD) 17.5. Except for Erp29, which remained stable, these Pdi transcript levels increased from GD17.5 to GD20.5, when epididymal morphogenesis occurs, and were maintained to varying degrees in the epididymis during postnatal development. Surgical castration downregulated P4hb, Pdia3, Pdia5, Pdia6, Pdilt and Erp29 transcripts, an effect reversed by testosterone replacement. Conversely, transcript levels remained unaffected by EDL, except P4hb, which was reduced in caput epididymis. All 21 PDI genes exhibited diverse transcriptional profiles across the human epididymis. DISCUSSION AND CONCLUSION: The findings lay the foundations to explore Pdi genes in epididymal biology. As a considerable proportion of male infertility cases are idiopathic, targeting hormonal regulation of protein quality control in epididymis represents a route to address male infertility and advance therapeutic interventions in this domain.

The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

Hormonal male contraception.

INTRODUCTION: Male contraception with exogenously administered hormones suppresses both luteinizing hormone and follicle stimulating hormone leading to low intratesticular testosterone concentration. This results in reversible suppression of spermatogenesis and marked decrease in sperm output in the ejaculate and preventing pregnancy in the female partner. PRIOR STUDIES: Studies of testosterone administered alone or in combination of another gonadotropin suppressive agent such as a progestin or gonadotropin releasing hormone (GnRH) analog showed decisively that the exogenous hormone administrations are effective in suppressing sperm output with few adverse events that are not anticipated. In contraceptive efficacy studies, testosterone alone or combined with a progestin are as effective in preventing pregnancies as female contraceptive methods. CONCLUSION: Hormone combinations for male contraception are in late-phase clinical trials and hold the promise of being the new, reversible contraception method for men in over half a century. Lessons learned from the male hormonal contraceptive development pave the way for new targeted approached to regulate male fertility.

Association between Disgust Sensitivity during Pregnancy and Endogenous Steroids: A Longitudinal Study.

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/ß-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/ß-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.

Exposure to Synthetic Endocrine-Disrupting Chemicals in Relation to Maternal and Fetal Sex Steroid Hormones: A Scoping Review.

PURPOSE OF REVIEW: Many synthetic endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment and highly detected among pregnant people. These chemicals may disrupt maternal and/or fetal sex steroid hormones, which are critical to pregnancy maintenance and fetal development. Here, we review the epidemiological literature examining prenatal exposure to common synthetic EDCs in relation to maternal and fetal sex steroid hormones. RECENT FINDINGS: We performed a literature search using PubMed, SCOPUS, and Embase, ultimately identifying 29 articles for full review. Phenols, parabens, and persistent organic pollutants generally showed inverse associations with androgens, estrogens, and progesterone. Phthalates and per-and polyfluoroalkyl substances tended to be inversely associated with progesterone, while evidence regarding androgens and estrogens was mixed. Inconsistent, but noteworthy, differences by fetal sex and timing of exposure/outcome were observed. Overall, the literature suggests EDCs may disrupt maternal and fetal sex steroid activity, though findings are mixed. Given the pervasive, high-volume production of these synthetic chemicals and the critical functions sex steroid hormones play during gestation, additional research is warranted.

Steroid sulfatase and sulfotransferases in the estrogen and androgen action of gynecological cancers: current status and perspectives.

Sulfatase (STS) and sulfotransferases (SULT) have important role in the biosynthesis and action of steroid hormones. STS catalyzes the hydrolysis of estrone-sulfate (E1-S) and dehydroepiandrosterone-sulfate (DHEA-S), while sulfotransferases catalyze the reverse reaction and require 3-phosphoadenosine-5-phosphosulfate as a sulfate donor. These enzymes control the concentration of active estrogens and androgens in peripheral tissues. Aberant expression of STS and SULT genes has been found in both, benign hormone-dependent diseases and hormone-dependent cancers. The aim of this review is to present the current knowledge on the role of STS and SULT in gynecological cancers, endometrial (EC) and ovarian cancer (OC). EC is the most common and OC the most lethal gynecological cancer. These cancers primarily affect postmenopausal women and therefore rely on the local production of steroid hormones from inactive precursors, either DHEA-S or E1-S. Following cellular uptake by organic anion transporting polypeptides (OATP) or organic anion transporters (OAT), STS and SULT regulate the formation of active estrogens and androgens, thus disturbed balance between STS and SULT can contribute to the onset and progression of cancer. The importance of these enzymes in peripheral estrogen biosynthesis has long been recognized, and this review provides new data on the important role of STS and SULT in the formation and action of androgens, their regulation and inhibition, and their potential as prognostic biomarkers.

Steroid metabolism and hormonal dynamics in normal and malignant ovaries.

The ovaries are key steroid hormone production sites in post-pubertal females. However, current research on steroidogenic enzymes, endogenous hormone concentrations and their effects on healthy ovarian function and malignant development is limited. Here, we discuss the importance of steroid enzymes in normal and malignant ovaries, alongside hormone concentrations, receptor expression and action. Key enzymes include STS, 3ß-HSD2, HSD17B1, ARK1C3, and aromatase, which influence ovarian steroidal action. Both androgen and oestrogen action, via their facilitating enzyme, drives ovarian follicle activation, development and maturation in healthy ovarian tissue. In ovarian cancer, some data suggest STS and oestrogen receptor α may be linked to aggressive forms, while various oestrogen-responsive factors may be involved in ovarian cancer metastasis. In contrast, androgen receptor expression and action vary across ovarian cancer subtypes. For future studies investigating steroidogenesis and steroidal activity in ovarian cancer, it is necessary to differentiate between disease subtypes for a comprehensive understanding.

Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series.

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that manifests clinically as recurrent episodes of swelling affecting multiple anatomical locations. Long-term prophylaxis (LTP) aims to control the disease by preventing HAE attacks. Previously, treatments such as attenuated androgens have been used for LTP, but they have an unfavorable adverse effect profile. Today, these limitations may be overcome by patients transitioning to newer, targeted therapies including oral berotralstat and subcutaneous lanadelumab. This case series reports the transition process between different prophylactic therapies in a family with HAE in a real-world setting. RESULTS: Four adult patient cases from the same family who underwent transitions in HAE prophylaxis are presented. Three were female and one male. Two patients who transitioned to berotralstat were initially prescribed attenuated androgens. Two patients were not taking LTP at the time of initiating targeted treatment but had previously been prescribed tranexamic acid. The length of transition varied between the patients, with the longest time taken to stabilize on new therapy being 26 months. All patients received regular follow-up in person or by telephone and all four required an adjustment from their initial treatment plan. CONCLUSIONS: Transitioning between LTP in HAE may help improve control of attacks, avoid unwanted adverse effects, or better cater to individual patient preferences. Newer targeted therapies have been shown to be effective and should be discussed with patients. Shared decision-making is a tool that can aid these discussions. The transition journey between LTP therapies in HAE may not be straightforward and is specific to each patient. Physicians should consider complicating factors such as patient anxieties around changing treatment, adverse effects, preferred routes of administration, and speed of transition. Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary.

Assessing the prevalence and knowledge of anabolic steroid use in male athletes in Al Madina Al Munawara, Saudi Arabia.

OBJECTIVES: To assess the prevalence of anabolic steroid use and the level of knowledge on anabolic steroids among the male athletes in Al Madina Al Munawara, Saudi Arabia. METHODS: A cross-sectional study was conducted on male athletes randomly selected from the private athletic centers in Al Madina Al Munawara over 5 months. Data were collected from all participants using a self-administered anonymous questionnaire with 33 questions. The questionnaire covered the socio-demographic characteristics of the participants, and their knowledge, attitudes, and use of anabolic steroids. RESULTS: Of the 150 male athletes surveyed, 121 completed the questionnaire (response rate: 80.6%). Over half were aged between 18 and 23 years (56.2%) and were single (79.3%). Thirty-two percent reported using anabolic steroids, mainly to increase muscle mass, following coaches' advice (46.1%). Key sources included the internet (30.7%), coaches (30%), and friends (27.9%), and non-healthcare professionals. The top motivations were price, coach's/physician's advice, and availability. The perceived benefits included increased muscle mass, strength, and endurance, while the perceived adverse effects included kidney/liver damage and sexual problems. CONCLUSION: One-third of the male athletes surveyed used anabolic steroids, influenced by accessibility and social contact, rather than healthcare guidance. This highlights the need for greater awareness of the long-term health risks, ideally through education provided by sports medicine specialists.

Simultaneous measurement of 17 endogenous steroid hormones in human serum by liquid chromatography-tandem mass spectrometry without derivatization.

Mass spectrometric-based steroidomics is a valuable analytical approach that gives a comprehensive understanding of the interlinked steroid biosynthetic pathways. Here, we describe a rapid and versatile liquid chromatography-tandem mass spectrometry (LC-MS/MS) method designed to accurately quantify endogenous steroids in human serum. Sample preparation involved liquid-liquid extraction with methyl tert-butyl ether (MTBE) from 180 µL serum. The targeted steroids for quantification included androgens: dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), dihydrotestosterone (DHT), 11-oxyandrogens: 11ß-hydroxy-androstenedione (11OHA4), 11-keto-androstenedione (11KA4), 11ß-hydroxy-testosterone (11OHT), 11-keto-testosterone (11KT), progestogens: 17α-hydroxy-progesterone (17OHP4), progesterone (P4), 11ß-hydroxy-progesterone (11OHP4), 11-keto-progesterone (11KP4), mineralocorticoids: aldosterone, corticosterone, and glucocorticoids: 11-deoxycortisol, cortisol, and cortisone. The lower limits of quantification (LLOQ) were 0.05 ng/mL for A4, T, 11KA4, P4, and cortisone, 0.1 ng/mL for DHT, 11OHA4, 11OHT, 11KT, 17OHP4, 11OHP4, 11KP4, corticosterone, aldosterone, 11-deoxycortisol, and cortisol, and 0.5 ng/mL for DHEA. Accuracy, precision, reproducibility, and recovery fell within acceptable limits for bioanalytical method validation. Using serum samples from 29 premenopausal women in different menstrual phases, we demonstrated the clinical utility of our method, which showed sufficient sensitivity to reliably quantify all targeted steroids at levels typically found in circulation, except for 11OHP4 and 11KP4.

Unraveling the anti-androgenic mechanism of tris(2,3-dibromopropyl) isocyanurate (TBC) via the non-classical testosterone pathway and steroidogenesis: Potential human reproductive health implications.

The decline in male reproductive health, characterized by diminishing sperm count and testosterone levels, has raised concerns about environmental influences, particularly endocrine-disrupting chemicals (EDCs). Tris(2,3-dibromopropyl)isocyanurate (TBC), a novel brominated flame retardant widely used in electronics, textiles, and furniture, has emerged as a significant environmental contaminant with potential reproductive health implications. In this study, we investigated the molecular mechanisms underlying TBC-induced reproductive toxicity, particularly focusing on its impact on steroidogenesis and androgen signaling pathways using the GC-1 spg cell line as an in vitro model. Exposure of GC-1 spg cells to TBC, alone or in combination with testosterone or the anti-androgen flutamide resulted in decreased metabolic activity and increased lactate dehydrogenase release, indicating cytotoxic effects. Furthermore, TBC exposure led to a reduction in progesterone synthesis, while testosterone production remained unaffected. Interestingly, estradiol synthesis was diminished after TBC exposure, suggesting a disruption in steroid hormone balance critical for spermatogenesis. Mechanistic investigations revealed alterations in key proteins involved in the non-classical testosterone pathway and steroidogenesis. TBC exposure downregulated epidermal growth factor receptor (EGFR), protein kinase B (AKT), and phosphorylated cyclic AMP response element-binding protein (p-CREB), indicating suppression of non-classical androgen signaling. Additionally, decreased levels of steroidogenic acute regulatory protein (StAR) and 3-beta-hydroxysteroid dehydrogenase (HSD3ß1) suggest impaired steroidogenesis. Here we uncover the intricate molecular mechanisms underlying TBC-induced reproductive toxicity, highlighting its potential to disrupt steroid hormone synthesis and androgen signaling pathways. Understanding the adverse effects of TBC on male reproductive health is crucial for developing strategies to mitigate its environmental impact and safeguard human fertility.

Sex, season, age and status influence urinary steroid hormone profiles in an extremely polygynous neotropical bat.

Several polygynous mammals exhibit reproductive skew in which only a few males reproduce. Successful males need strength, stamina and fighting ability to exclude competitors. Consequently, during the mating season their androgens and glucocorticoids are expected to increase to support spermatogenesis and aggressive behavior. But, during the nonmating season these hormones should decline to minimize deleterious effects, such as reduced immune function. Bats that exhibit harem polygyny in which males aggressively defend large groups of females year-round are ideal for assessing hormonal and other consequences of extreme polygyny. Here we use DNA methylation to estimate age and gas chromatography, tandem mass spectrometry to profile steroid metabolites in urine of wild greater spear-nosed bats, Phyllostomus hastatus, across seasons. We find that condition, measured by relative weight, is lower during the mating season for both sexes, although it remains high in harem males during the mating season. Average age of females is greater than males, and females exhibit substantial seasonal differences in androgens, estrogens and glucocorticoids with higher levels of all hormones during the mating season. Males, however, show little seasonal differences but substantial age-associated increases in most steroid metabolites. Harem males have larger, persistently scrotal testes and are older than bachelor males. While cortisone generally declines with age, harem males maintain higher amounts of biologically active cortisol than bachelor males all year and cortisol levels increase more quickly in response to restraint in males than in females. Taken together, these results suggest that attaining reproductive dominance requires hormone levels that reduce lifespan.

Serum androgen dynamics in young women aged 18-40 treated with chemotherapy for breast cancer: an observational, multicentric, prospective study in France.

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464.

Risks associated with cognitive function and management strategies in the clinical use of ADT: a systematic review from clinical and preclinical studies.

Prostate cancer is one of the most common malignancies and a leading cause of death in men. Owing to its excellent anti-tumor effects, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer. However, its use is controversial because of its potential for inducing cognitive decline. In this review, we summarized the findings of preclinical and clinical studies investigating the effects of ADT on cognitive function in prostate cancer. We discussed the methods used to assess cognitive function in these studies, elucidated the mechanisms through which ADT affects cognitive function, and highlighted recent advancements in cognitive assessment methods. The findings of this review serve as a valuable reference for examining the relationship between ADT and cognitive function in future studies. Besides, the findings may help clinicians understand the advantages and disadvantages of ADT and optimize the treatment plan so as to minimize the adverse effects of ADT.

Impact of trenbolone on selected organs.

Trenbolone is a synthetic analogue of testosterone, belonging to the nandrolone group. It has both a strong anabolic effect and a limited androgenic effect (i.e. an androgen and anabolic steroid - AAS). It is used illegally by professional or amateur athletes, who want to improve their athletic performance and appearance by increasing their muscle mass. Trenbolone, like other AASs, are harmful, with 90% of users experiencing injurious side effects. It acts systemically on the body, and as such, its side effects can manifest as symptoms from different systems. Nevertheless, its popularity is increasing. This paper reviews the current state of knowledge regarding the adverse effects of trenbolone on the nervous, reproductive, immune systems and breast, muscular and adipose tissues. However, various other adverse consequences of trenbolone utilization are observed, with severe acne and gynaecomastia affecting approximately one-third of all users, as well as excessive body hair, stretch marks, hypertension and cardiac arrhythmia. The drugs are also subject to contamination, with use frequently resulting in local inflammation at the injection site, muscle adhesions and fibrosis, nerve damage or, in extreme cases, necrosis of the injection site. Additionally, due to the lack of available knowledge on the subject, many of the effects of trenbolone use remain unknown. Moreover, the fact that multiple AASs may be used simultaneously presents a significant problem in their study. Therefore, further research is necessary to better understand the effects of AAS on the body, and to expand our currently incomplete knowledge of their functional pathways.

Stability of steroid hormones in dried blood spots (DBS).

OBJECTIVES: Steroid hormone levels of patients may be monitored via dried blood spot (DBS) sampling at home. Stability of steroid hormones in DBS samples, however, needs to be established. METHODS: DBS samples from healthy volunteers were collected and stored at various temperatures. Steroid hormone concentrations in DBS were measured directly, at day 2, day 7 and day 14 following storage at 37 °C and after 7 days, 14 days, 3 months and 6 months following storage at -20 °C, 4 °C and room temperature (RT). Cortisol, cortisone, corticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were assessed using LC-MS/MS. RESULTS: All steroids were stable (±15 %) up to 14 days when stored at 37 °C, except for cortisone (only stable until 2 days). All steroids were stable up to 6 months when stored at -20 °C, 4 °C and RT. However, there were some exceptions, for androstenedione at RT (only stable until 7 days), for 17-OHP when stored at -20 °C (only stable until 3 months), for cortisone at RT and 4 °C (only stable until 14 days), and cortisol at RT (only stable until 3 months). CONCLUSIONS: Overall, we demonstrated stability of steroid hormone concentrations in DBS under various conditions which may be encountered during shipping to the diagnostic laboratory and during long-term storage before analysis.

Species variation in steroid hormone-related gene expression contributes to species diversity in sexually dimorphic communication in electric fishes.

Sexually dimorphic behaviors are often regulated by gonadal steroid hormones. Species diversity in behavioral sex differences may arise as expression of genes mediating steroid action in brain regions controlling these behaviors evolves. The electric communication signals of apteronotid knifefishes are an excellent model for comparatively studying neuroendocrine regulation of sexually dimorphic behavior. These fish produce and detect weak electric organ discharges (EODs) for electrolocation and communication. EOD frequency (EODf), controlled by the medullary pacemaker nucleus (Pn), is sexually dimorphic and regulated by androgens and estrogens in some species, but is sexually monomorphic and unaffected by hormones in other species. We quantified expression of genes for steroid receptors, metabolizing enzymes, and cofactors in the Pn of two species with sexually dimorphic EODf (Apteronotus albifrons and Apteronotus leptorhynchus) and two species with sexually monomorphic EODf ("Apteronotus" bonapartii and Parapteronotus hasemani). The "A." bonapartii Pn expressed lower levels of androgen receptor (AR) genes than the Pn of species with sexually dimorphic EODf. In contrast, the P. hasemani Pn robustly expressed AR genes, but expressed lower levels of genes for 5α-reductases, which convert androgens to more potent metabolites, and higher levels of genes for 17ß-hydroxysteroid dehydrogenases that oxidize androgens and estrogens to less potent forms. These findings suggest that sexual monomorphism of EODf arose convergently via two different mechanisms. In "A." bonapartii, reduced Pn expression of ARs likely results in insensitivity of EODf to androgens, whereas in P. hasemani, gonadal steroids may be metabolically inactivated in the Pn, reducing their potential to influence EODf.

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Alcohol intake and endogenous sex hormones in women: Meta-analysis of cohort studies and Mendelian randomization.

BACKGROUND: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. METHODS: Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984). RESULTS: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively). CONCLUSIONS: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.

Endogenous androgens, coronary atheroma and remodeling in women with suspected ischemic heart disease: A report from the Women's Ischemia Syndrome Evaluation (WISE) study.

Background: Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose: To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods: We analyzed 69 women with available androgen levels. Results: Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = -0.26, p = 0.03; r = -0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions: In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.