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The vagina as source and target of androgens: implications for treatment of GSM/VVA, including DHEA.Climacteric : the Journal of the... Aug 2023The vagina is traditionally thought of as a passive organ in the female reproductive system, serving primarily as a passageway for menstrual blood, sexual intercourse... (Review)
Review
The vagina is traditionally thought of as a passive organ in the female reproductive system, serving primarily as a passageway for menstrual blood, sexual intercourse and childbirth. However, recent research has shed light on the vagina's role as an endocrine organ that plays a crucial role in female hormonal balance and overall health. Particularly, growing evidence shows that the human vagina can be considered both as source and target of androgens, in view of the novel concept of 'intracrinology'. Besides the well-known role of estrogens, androgens are also crucial for the development and maintenance of healthy genitourinary tissues in women. As androgen levels decline with age, and estrogen levels fall during the menopausal transition, the tissues in the vagina, together with those in the urinary tract, become thinner, drier and less elastic, leading to a variety of uncomfortable and sometimes painful symptoms, clustered in the genitourinary syndrome of menopause (GSM). Given the lack of testosterone-based or androstenedione-based products approved by regulatory agencies to treat GSM, the possibility of using intravaginal prasterone, which works by providing a local source of dehydroepiandrosterone (DHEA) to the vaginal tissues, appears to be a targeted treatment. Further studies are needed to better assess its safety and efficacy.
Topics: Female; Humans; Androgens; Dehydroepiandrosterone; Dyspareunia; Administration, Intravaginal; Vagina; Menopause; Estrogens; Atrophy
PubMed: 37288964
DOI: 10.1080/13697137.2023.2213827 -
Biomolecules Nov 2022Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone,... (Review)
Review
Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). These steroids modulate the development and function of immune response cells. Androgens are generally attributed to immunosuppressive effects; however, this is not always the case. Variations in the concentrations of these hormones induce differences in the innate, humoral, and cell-mediated immune response, which is concentration dependent. The androgens at the highest concentration in the organism that bind to the androgen receptor (AR) are DHEA and testosterone. Therefore, in this work, we review the effects of DHEA and testosterone on the immune response. The main findings of this review are that DHEA and testosterone induce similar but also opposite effects on the immune response. Both steroids promote the activation of regulatory T cells, which suppresses the Th17-type response. However, while testosterone suppresses the inflammatory response, DHEA promotes it, and this modulation is important for understanding the involvement of androgens in infectious (bacterial, viral and parasitic) and autoimmune diseases, as well as in the sexual dimorphism that occurs in these diseases.
Topics: Testosterone; Dehydroepiandrosterone; Androgens; Dihydrotestosterone; Adaptive Immunity
PubMed: 36551196
DOI: 10.3390/biom12121768 -
Expert Opinion on Pharmacotherapy Jan 2023Genitourinary syndrome of menopause is caused by climacteric estrogens drop and leads to bothersome and progressive genital and urinary symptoms. Considering the high... (Review)
Review
INTRODUCTION
Genitourinary syndrome of menopause is caused by climacteric estrogens drop and leads to bothersome and progressive genital and urinary symptoms. Considering the high frequency in the population and the impact on quality of life, it is crucial to find a safe and effective treatment. Pharmacological therapies aim to modulate the hormonal system and reverse tissue changes due to hypoestrogenism and consequently the symptoms.
AREAS COVERED
We analyzed the scientific evidence concerning the main pharmacological treatments, which include systemic and topical estrogens, prasterone and ospemifene. This literature review focused on recent safety and efficacy findings in an attempt to identify the best treatment choice for each individual patient.
EXPERT OPINION
There are encouraging data regarding the efficacy of all currently available pharmacological options and concerning their short and long-term safety. There are still doubts regarding best treatment choice for oncological high-risk population, in particular for breast cancer survivors, and some issues relative to patients' poor compliance and treatment adherence. For these reasons further studies need to be conducted with a patient-tailored focus.
Topics: Female; Humans; Quality of Life; Menopause; Breast Neoplasms; Estrogens; Dehydroepiandrosterone; Syndrome; Vagina; Atrophy
PubMed: 36444726
DOI: 10.1080/14656566.2022.2152326 -
Life Sciences Oct 2023The present study aims to investigate the impact of the gut microbiota and serum metabolites on the regulation of liver dysfunction in PCOS.
AIMS
The present study aims to investigate the impact of the gut microbiota and serum metabolites on the regulation of liver dysfunction in PCOS.
MATERIALS AND METHODS
PCOS rat models were established by treating Sprague Dawley (SD) rats with DHEA (an androgen, 60 mg/kg) and LET (a nonsteroidal aromatase inhibitor, 1 mg/kg) for 90 days. Hematoxylin and eosin staining (H&E), Western blotting, and radioimmunoassay were employed to test ovarian and liver functions. Gut microbiome and serum metabolites were assessed using 16S rRNA amplicon sequencing and non-targeted metabolomics, respectively. The association between gut microbiota and serum metabolites was examined using Spearman analysis. Finally, using HepG2 cells to investigate the function of the serum metabolite rosmarinic acid (RA).
KEY FINDINGS
Both Dehydroepiandrosterone (DHEA) and letrozole (LET) treatments induced a PCOS phenotype and liver dysfunction. However, LET resulted in more severe lipid accumulation and liver cell apoptosis than DHEA. 16S rRNA sequencing and non-targeted metabolomics analysis revealed significant differences in beta diversity and serum metabolite profiles among the three groups. Furthermore, among the significantly changed metabolites, RA was found to have a significant correlation with the levels of serum aspartate transaminase (AST) and lactate dehydrogenase (LDH) and could promote HepG2 cell apoptosis.
SIGNIFICANCE
Restoring gut microbiota, altering serum metabolites and/or decreasing RA may provide a new insight to treat this complication.
Topics: Humans; Female; Rats; Animals; Polycystic Ovary Syndrome; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Rats, Sprague-Dawley; Letrozole; Liver Diseases; Dehydroepiandrosterone; Rosmarinic Acid
PubMed: 37423380
DOI: 10.1016/j.lfs.2023.121912 -
Trends in Endocrinology and Metabolism:... Sep 2020Dehydroepiandrosterone (DHEA) and DHEA sulfate together are abundant adrenal steroids whose physiological effects are mediated through their conversion to potent... (Review)
Review
Dehydroepiandrosterone (DHEA) and DHEA sulfate together are abundant adrenal steroids whose physiological effects are mediated through their conversion to potent downstream androgens. 3β-Hydroxysteroid dehydrogenase isotype 1 (3βHSD1) facilitates the rate-limiting step of DHEA metabolism and gates the flux of substrate into the distal portion of the androgen synthesis pathway. Notably, a germline, missense-encoding change, HSD3B1(1245C), results in expression of 3βHSD1 protein that is resistant to degradation, yielding greater potent androgen production in the periphery. In contrast, HSD3B1(1245A) encodes 3βHSD1 protein that is easily degraded, limiting peripheral androgen synthesis. These adrenal-permissive (AP) and adrenal-restrictive (AR) alleles have recently been associated with divergent outcomes in androgen-sensitive disease states, underscoring the need to reevaluate DHEA metabolism using HSD3B1 genetics.
Topics: 3-Hydroxysteroid Dehydrogenases; Androgens; Animals; Dehydroepiandrosterone; Humans; Male; Progesterone Reductase
PubMed: 32565196
DOI: 10.1016/j.tem.2020.05.006 -
JAAPA : Official Journal of the... Dec 2019In small clinical trials, dehydroepiandrosterone (DHEA) has been found to relieve symptoms associated with postmenopausal conditions and infertility in women. DHEA may...
In small clinical trials, dehydroepiandrosterone (DHEA) has been found to relieve symptoms associated with postmenopausal conditions and infertility in women. DHEA may provide a cost-effective alternative to typical hormone therapies. Because of a lack of long-term and large-scale studies, only intravaginal DHEA supplementation is approved and recommended for treatment. Further investigation of DHEA supplementation is needed and encouraged to determine its safety and effectiveness.
Topics: Administration, Intravaginal; Administration, Oral; Atrophy; Dehydroepiandrosterone; Dyspareunia; Female; Gynecology; Humans; Menopause; Reproductive Techniques, Assisted; Vaginal Diseases; Vulvar Diseases
PubMed: 31770299
DOI: 10.1097/01.JAA.0000604888.50734.64 -
Reproductive Biology and Endocrinology... Apr 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear.
METHODS
A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy.
RESULTS
Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR.
CONCLUSION
In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.
Topics: Male; Pregnancy; Female; Infant, Newborn; Humans; Polycystic Ovary Syndrome; Androgens; Dehydroepiandrosterone Sulfate; Retrospective Studies; Semen; Dehydroepiandrosterone
PubMed: 38627777
DOI: 10.1186/s12958-024-01212-y -
Frontiers in Immunology 2022Effective control of () infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different...
Effective control of () infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different stages of TB provides insight in the pathogenesis of the disease. In this study, we profiled endocrine hormones (dehydroepiandrosterone (DHEA), cortisol, testosterone, estradiol, growth hormone and leptins) and strain H37RV lipoarabinomannan (LAM)-specific antibody levels in plasma samples, collected from pulmonary TB (PTB) patients, TB lymphadenitis (TBLN) patients and latently infected (QFT-positive) or uninfected (QFT-negative) apparently healthy individuals using ELISA. Plasma levels of leptin and DHEA were significantly low in PTB and TBLN patients compared to healthy controls (P<0.0001 and P=0.02, respectively), whereas these levels significantly increased following anti-TB treatment (P=0.002 and P=0.0001, respectively) among TB patients. The levels of estradiol and testosterone significantly improved following anti-TB treatment (P=0.03 and P=0.0003, respectively), whereas cortisol and growth hormones declined significantly (P <0.05). Similarly, LAM-specific IgG, IgM and IgA were significantly higher in PTB patients compared to other groups, whereas levels of IgG1 subtype were significantly higher among LTBI groups compared to both TB patients and QFT-negative individuals (P<0.0001). Overall, we observed significantly variable levels of endocrine hormones as well as immunoglobulins across the spectrum of TB illness and such profiling has a significant contribution in selection of effective biomarkers that have roles in TB treatment monitoring or diagnostics. Although this study did not show a functional association between hormones and antibodies, alterations in the levels of these biomarkers suggest the key roles these markers play in TB pathogenesis.
Topics: Antibody Formation; Biomarkers; Dehydroepiandrosterone; Estradiol; Humans; Hydrocortisone; Testosterone; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 35281036
DOI: 10.3389/fimmu.2022.849321 -
Hormones (Athens, Greece) Mar 2023
Topics: Humans; Hydrocortisone; COVID-19; Dehydroepiandrosterone Sulfate; Dehydroepiandrosterone
PubMed: 36374475
DOI: 10.1007/s42000-022-00417-3 -
Drug Discoveries & Therapeutics May 2023Diminished ovarian reserve (DOR) refers to the decline in fertility caused by the loss of normal ovarian function. DOR is associated with adverse reactions to ovarian... (Review)
Review
Diminished ovarian reserve (DOR) refers to the decline in fertility caused by the loss of normal ovarian function. DOR is associated with adverse reactions to ovarian stimulation during in vitro fertilization and embryo transfer (IVF-ET), increasing cycle cancellation rates and reducing pregnancy rates. Although it is well known that dehydroepiandrosterone (DHEA) can be used as a dietary supplement for age-related diseases, its potential has gradually been shown for many diseases. In this review, we focus on the effects of DHEA on DOR, briefly analysing its clinical benefits and limitations and describing the mechanism of function and the clinical trials conducted. Therefore, we summarize the mechanisms and indications of DHEA for DOR.
Topics: Pregnancy; Female; Humans; Dehydroepiandrosterone; Ovarian Reserve; Fertilization in Vitro; Pregnancy Rate; Ovary
PubMed: 37019659
DOI: 10.5582/ddt.2022.01109