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Gynecologie, Obstetrique, Fertilite &... Sep 2023Uterine transplantation is now a possible treatment for absolute uterine infertility. It is currently proposed to women with Mayer-Rokitansky-Küster-Hauser syndrome but... (Review)
Review
Uterine transplantation is now a possible treatment for absolute uterine infertility. It is currently proposed to women with Mayer-Rokitansky-Küster-Hauser syndrome but indications will likely to expand in the upcoming years. Despite the progressive standardization of the surgical technique and the reduction in perioperative morbidity for both donors and recipients, the number of transplants performed worldwide remains very low compared to the number of women potentially in need. This is partly due to the singularity of uterine transplantation: the uterus is not a vital organ since one can live without a uterus. It is a temporary transplantation that is not performed to extend life but to improve its quality, responding above all to a desire to conceive and bear a child. Beyond the strictly technical aspect, these particularities raise many ethical questions, both on an individual and social level, which should make us question the real place uterine transplantation should take in our society. Answering these questions will allow us to provide better guidance for future eligible couples and to anticipate ethical problems on the long run.
Topics: Female; Humans; 46, XX Disorders of Sex Development; Forecasting; Infertility, Female; Tissue Donors; Uterus
PubMed: 37024089
DOI: 10.1016/j.gofs.2023.03.009 -
Frontiers in Endocrinology 2024
Topics: Turner Syndrome; Humans; Female; Adult; Young Adult; Transition to Adult Care; Adolescent
PubMed: 38859906
DOI: 10.3389/fendo.2024.1431972 -
Medicine Dec 2023Polycystic ovary syndrome (PCOS) is a complex disorde7r influenced by genetic, neuroendocrine, metabolic, environmental, and lifestyle factors. This paper delves into... (Review)
Review
Polycystic ovary syndrome (PCOS) is a complex disorde7r influenced by genetic, neuroendocrine, metabolic, environmental, and lifestyle factors. This paper delves into the increasingly recognized role of gut microbiota dysbiosis in the onset and progression of PCOS. Utilizing advances in next-generation sequencing and metabolomics, the research examines the intricate interaction between the gut microbiota and the central nervous system via the gut-brain axis. The paper highlights how disruptions in gut microbiota contribute significantly to PCOS by modulating the release of gut-brain peptides and activating inflammatory pathways. Through such mechanisms, gut microbiota dysbiosis is implicated in hyperandrogenism, insulin resistance, chronic inflammation, and metabolic disorders associated with PCOS. While the relationship between gut microbiota and PCOS has begun to be elucidated, this paper underscores the need for further research to identify specific bacterial strains and their metabolic byproducts as potential therapeutic targets. Therefore, comprehensive studies are urgently needed to understand and fundamentally treat the pathophysiological processes of PCOS, offering valuable insights for future treatment and prevention strategies.
Topics: Female; Humans; Polycystic Ovary Syndrome; Gastrointestinal Microbiome; Dysbiosis; Hyperandrogenism; Insulin Resistance
PubMed: 38115365
DOI: 10.1097/MD.0000000000036075 -
Frontiers in Endocrinology 2023Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no cure for PCOS, and current treatments primarily alleviate its symptoms due to a poor understanding of its etiology. Compelling evidence suggests that hyperandrogenism is not just a primary feature of PCOS. Instead, it may be a causative factor for this condition. Thus, figuring out the mechanisms of androgen synthesis, conversion, and metabolism is relatively important. Traditionally, studies of androgen excess have largely focused on classical androgen, but in recent years, adrenal-derived 11-oxygenated androgen has also garnered interest. Herein, this Review aims to investigate the origins of androgen excess, androgen synthesis, how androgen receptor (AR) signaling mediates adverse PCOS traits, and the role of 11-oxygenated androgen in the pathophysiology of PCOS. In addition, it provides therapeutic strategies targeting hyperandrogenism in PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Androgens; Phenotype
PubMed: 38152131
DOI: 10.3389/fendo.2023.1273542 -
Endocrine Journal Oct 2023Optimizing the glucocorticoid dosage has been a major concern in classic 21OHD (21-hydroxylase deficiency) treatment, as it is essential to adjust it meticulously to the... (Review)
Review
Optimizing the glucocorticoid dosage has been a major concern in classic 21OHD (21-hydroxylase deficiency) treatment, as it is essential to adjust it meticulously to the needs of the individual patient. Insufficient glucocorticoid treatment will cause adrenal insufficiency, including life-threatening adrenal crisis, while excess of androgen could cause precocious pubertal growth in children, virilization in female patients, and infertility in male and female adult patients. Meanwhile, overtreatment with glucocorticoids causes iatrogenic Cushing's syndrome which could result in growth impairment, obesity, osteoporosis, and hypertension. The dilemma of 21OHD treatment is that glucocorticoid supplementation therapy at physiological dosage does not sufficiently suppress ACTH, consequently leading to adrenal androgen excess. Accordingly, the window for the appropriate glucocorticoid treatment would have to be substantially narrower than that of other types of adrenal insufficiency without androgen excess, such as adrenal hypoplasia. For the appropriate management of classic 21OHD, the physician has to be well versed in the physiology of the adrenal cortex, growth, and reproductive function. Comprehensive understanding of patients' requirements according to their life stage and sex is essential. Furthermore, female patients with 46,XX need to be cared for as differences in sex development (DSD) with careful psychological management. In this review, we aimed to comprehensively summarize the current status of classic 21OHD treatment, including the initial treatment during the neonatal period, management of adrenal insufficiency, maintenance therapy of each life stage, and the importance of clinical management as DSD for 46,XX female patients. The recently developed agents, Chronocort, and Crinecerfont, are also discussed.
Topics: Adult; Child; Infant, Newborn; Humans; Male; Female; Glucocorticoids; Androgens; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Steroid 21-Hydroxylase
PubMed: 37380491
DOI: 10.1507/endocrj.EJ23-0075 -
Journal of Ovarian Research Jul 2023Polycystic ovary syndrome (PCOS) is known as a prevalent but complicated gynecologic disease throughout the reproductive period. Typically, it is characterized by... (Review)
Review
Polycystic ovary syndrome (PCOS) is known as a prevalent but complicated gynecologic disease throughout the reproductive period. Typically, it is characterized by phenotypic manifestations of hyperandrogenism, polycystic ovary morphology, and persistent anovulation. For now, the therapeutic modality of PCOS is still a formidable challenge. Metabolic aberrations and immune challenge of chronic low-grade inflammatory state are significant in PCOS individuals. Recently, interleukin-22 (IL-22) has been shown to be therapeutically effective in immunological dysfunction and metabolic diseases, which suggests a role in the treatment of PCOS. In this review, we outline the potential mechanisms and limitations of IL-22 therapy in PCOS-related metabolic disorders including its regulation of insulin resistance, gut barrier, systemic inflammation, and hepatic steatosis to generate insights into developing novel strategies in clinical practice.
Topics: Female; Humans; Polycystic Ovary Syndrome; Interleukins; Hyperandrogenism; Anovulation; Insulin Resistance; Metabolic Syndrome; Interleukin-22
PubMed: 37525285
DOI: 10.1186/s13048-023-01236-9 -
International Immunopharmacology Dec 2023Hyperandrogenemia and persistent chronic inflammation, two main striking features of polycystic ovary syndrome (PCOS), have been proven involved in follicular dysgenesis...
Hyperandrogenemia and persistent chronic inflammation, two main striking features of polycystic ovary syndrome (PCOS), have been proven involved in follicular dysgenesis in PCOS. However, the association between hyperandrogenism and inflammation activation in PCOS is not fully understood. Excess testosterone(T) induces inflammation and pyroptosis activation in a mouse model of PCOS, leading to ovarian dysfunction and fibrosis. Excessive endoplasmic reticulum (ER) stress is present in ovarian granulosa cells (GCs), testosterone-induced PCOS mouse and cellular models. This study found higher levels of interleukin (IL)-1β, IL-8, IL-17, and IL-18 in the follicular fluid of PCOS patients with hyperandrogenemia undergoing IVF treatment. In addition, pyroptosis in GCs was demonstrated, which was significantly elevated in PCOS patients. To clarify the association of hyperandrogenism, inflammation, and pyroptosis activation in PCOS, dehydroepiandrosterone(DHEA)-treated mouse PCOS model and T-treated KGN cell line were explored for PCOS mechanism. Markers of inflammatory activation and pyroptosis were significantly increased after DHEA treatment in mice and T treatment in KGN cells. In addition, ER stress sensor proteins were increased simultaneously. However, suppression of inflammation by genipin(GP) led to decreased pyroptosis in KGN cells but no variation in ER stress sensor proteins. In contrast, when treated with tauroursodeoxycholic acid(TUDCA) to attenuate ER stress, the markers of inflammatory factors were significantly reduced, accompanied by a reduction in pyroptosis. Our results suggest that persistent hyperandrogenemia of PCOS promotes local inflammatory activation of the ovary, and the imbalanced inflammatory microenvironment leads to pyroptosis of GCs, which is mediated by ER stress activation.
Topics: Humans; Female; Mice; Animals; Polycystic Ovary Syndrome; Hyperandrogenism; Pyroptosis; Testosterone; Inflammation; Dehydroepiandrosterone; Tumor Microenvironment
PubMed: 37918087
DOI: 10.1016/j.intimp.2023.111141 -
Human Reproduction (Oxford, England) Nov 2023What is the relationship of sex steroid levels with sexual function in women with and without polycystic ovary syndrome (PCOS)? (Observational Study)
Observational Study
STUDY QUESTION
What is the relationship of sex steroid levels with sexual function in women with and without polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Women with PCOS reported more sexual dysfunction and more sexual distress compared to those without PCOS, but only few and weak associations between androgen levels and sexual function were observed.
WHAT IS KNOWN ALREADY
The literature shows that women with PCOS report lower levels of sexual function and sexual satisfactionand more sexual distress. Contributing factors seem to be obesity, alopecia, hirsutism, acne, infertility, anxiety, depression, and low self-esteem. In women with PCOS clinical and/or biochemical hyperandrogenism is common; its relationship with sexualfunction is, however, inconclusive.
STUDY DESIGN, SIZE, DURATION
This observational prospective case control study with 135 women (68 PCOS, 67 control) was conductedfrom March 2017 until March 2020.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Heterosexual women with and without PCOS, aged 18-40 years, in a steady relationshipand without any comorbidities, underwent an extensive medical and endocrine screening using liquid chromatography-tandem mass spectrometry and validated sexual function questionnaires.
MAIN RESULTS AND THE ROLE OF CHANCE
Women with PCOS reported significantly lower sexual function (Female Sexual Function Index (FSFI) P < 0.001, partial η2 = 0.104), higher levels of sexual distress (Female Sexual Distress Scale-Revised P < 0.001, partial η2 = 0.090), and they more often complied with the definition of sexual dysfunction (41.2% vs 11.9%, P < 0.001, Phi V = 0.331) and clinical sexual distress (51.5% vs 19.4%, P < 0.001, Phi V = 0.335). Regression analysis adjusted for confounders showed only few and weak associations between androgen levels and sexual function, with each model explaining a maximum of 15% sexual function. Following significant Group × Hormone interactions, analyses for both groups separately showed no significant associations in the PCOS group. The control group showed only weak negative associations between testosterone and FSFI pain (β = -6.022, P = 0.044, Adj R2 = 0.050), between FAI and FSFI orgasm (β = -3.360, P = 0.023, Adj R2 = 0.049) and between androstenedione and clinical sexual distress (β = -7.293, P = 0.036, exp(β) = 0.001).
LIMITATIONS, REASONS FOR CAUTION
The focus of the study on sexual functioning potentially creates selection bias. Possibly women with more severe sexual disturbances did or did not choose to participate. Differences between women with PCOS and controls in relationship duration and hormonal contraceptive use might have skewed the sexual function outcomes.
WIDER IMPLICATIONS OF THE FINDINGS
Sexual function is impaired in women with PCOS. However, endocrine perturbations seem to have minimal direct impact on sexual function. Addressing sexuality and offering psychosexual counseling is important in the clinical care for women with PCOS.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the departments of the participating centers: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Psychosomatic OBGYN and Sexology, Leiden University Medical Center, Leiden, the Netherlands; and Department of Sexology and Psychosomatic OBGYN, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. J.S.E.L. received unrestricted research grants from the following companies (in alphabetical order): Ansh Labs, Ferring, Merck Serono and Roche Diagnostics. He also received consultancy fees from Ansh Labs, Ferring, Titus Healthcare and Roche Diagnostics. The other authors have no conflicts of interest.
TRIAL REGISTRATION NUMBER
CCMO register, registration number: NL55484.078.16, 10 March 2016. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.
Topics: Female; Humans; Male; Pregnancy; Androgens; Case-Control Studies; Hyperandrogenism; Infertility, Female; Polycystic Ovary Syndrome; Sexual Dysfunction, Physiological; Prospective Studies
PubMed: 37776157
DOI: 10.1093/humrep/dead193 -
Current Cardiology Reports Jun 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric... (Review)
Review
PURPOSE OF REVIEW
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric disorders. Despite its association with insulin resistance (IR) and cardiovascular disease (CVD) risk factors, the association between PCOS and CVD outcomes has been conflicting. This review reports the updated evidence between PCOS, insulin resistance, and CVD events.
RECENT FINDINGS
IR is highly prevalent occurring in 50 to 95% of general and obese PCOS women. The etiology of PCOS involves IR and hyperandrogenism, which lead to CVD risk factors, subclinical CVD, and CVD outcomes. Multiple studies including meta-analysis confirmed a strong association between PCOS and CVD events including ischemic heart disease, stroke, atrial fibrillation, and diabetes, particularly among premenopausal women, and these associations were mediated by metabolic abnormalities. PCOS is highly familial and has substantial CVD risk and transgenerational effects regardless of obesity. A personalized approach to the CVD risk assessment and management of symptom manifestations should be conducted according to its phenotypes. Lifestyle modifications and reduction in environmental stressors should be encouraged for CVD prevention among PCOS women.
Topics: Humans; Polycystic Ovary Syndrome; Insulin Resistance; Female; Cardiovascular Diseases; Obesity; Risk Factors; Risk Assessment; Heart Disease Risk Factors; Prevalence; Hyperandrogenism
PubMed: 38568339
DOI: 10.1007/s11886-024-02050-5 -
International Journal of Women's... Oct 2023Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal,... (Review)
Review
BACKGROUND
Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex.
OBJECTIVE
Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD.
DATA SOURCES
Published articles including case series and case reports on PubMed.
STUDY SELECTIONS
Selection was conducted by examining existing literature with a team of multidisciplinary specialists.
METHODS
Narrative review.
LIMITATIONS
This article was not conducted as a systematic review.
RESULTS
In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common.
CONCLUSION
Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.
PubMed: 37671254
DOI: 10.1097/JW9.0000000000000106