-
International Journal of Molecular... Nov 2019Sex development is a complex process involving many genes and hormones. Defects in this process lead to Differences of Sex Development (DSD), a group of heterogeneous... (Review)
Review
Sex development is a complex process involving many genes and hormones. Defects in this process lead to Differences of Sex Development (DSD), a group of heterogeneous conditions not as rare as previously thought. Part of the obstacles in proper management of these patients is due to an incomplete understanding of the genetics programs and molecular pathways involved in sex development and DSD. Several challenges delay progress and the lack of a proper model system for the single patient severely hinders advances in understanding these diseases. The revolutionary techniques of cellular reprogramming and guided in vitro differentiation allow us now to exploit the versatility of induced pluripotent stem cells to create alternatives models for DSD, ideally on a patient-specific personalized basis.
Topics: Animals; Cellular Reprogramming Techniques; Disorders of Sex Development; Gonads; Humans; Induced Pluripotent Stem Cells; Patient-Specific Modeling; Primary Cell Culture
PubMed: 31690065
DOI: 10.3390/ijms20215495 -
Seminars in Reproductive Medicine Oct 2012Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene... (Review)
Review
Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene encoding Sf-1 (Nr5a1) in mice results in severe developmental defects of the adrenal gland and gonad. Consequently, initial work on the potential effects of SF-1 disruption in humans focused on individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis, and Müllerian structures. This is a rare phenotype, but has been reported on two occasions, because of alterations that affect key DNA-binding domains of SF-1. Attention then turned to a potential wider role of SF-1 in human adrenal and reproductive disorders. Although changes in SF-1 only very rarely cause isolated adrenal failure, it is emerging that variations in SF-1 are a surprisingly frequent cause of reproductive dysfunction in humans. In 46,XY disorders of sex development, a spectrum of phenotypes has been reported including severe and partial forms of gonadal (testicular) dysgenesis, hypospadias, anorchia with microphallus, and even male factor infertility. In 46,XX females, alterations in SF-1 are associated with primary ovarian insufficiency. Thus, SF-1 seems be a more significant factor in human reproductive health than was first envisioned, with implications for adults as well as children.
Topics: 46, XX Disorders of Sex Development; Adrenal Insufficiency; Animals; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Humans; Male; Mutation; Steroidogenic Factor 1
PubMed: 23044873
DOI: 10.1055/s-0032-1324720 -
American Family Physician Jul 1999Normal puberty begins between eight and 14 years of age in girls and between nine and 14 years of age in boys. Pubic hair distribution is used to stage puberty, along... (Review)
Review
Normal puberty begins between eight and 14 years of age in girls and between nine and 14 years of age in boys. Pubic hair distribution is used to stage puberty, along with breast size and contour in girls and testicular volume in boys. Some children experience constitutional sexual precocity, but precocity is likely to be pathologic if it occurs in very young children, if there is contrasexual development or if the sequence of normal pubertal milestones is disrupted. Delayed puberty may be constitutional, but pathologic causes should be considered. The etiology of a pubertal disorder can often be determined with the use of a focused medical history, a directed physical examination and appropriate diagnostic tests. Treatment for disorders of puberty is determined by the underlying cause.
Topics: Adolescent; Child; Diagnosis, Differential; Female; Humans; Male; Patient Education as Topic; Puberty; Puberty, Delayed; Puberty, Precocious; Teaching Materials
PubMed: 10414639
DOI: No ID Found -
Organogenesis Jan 2016Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent... (Review)
Review
Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system.
Topics: Disorders of Sex Development; Female; Gonads; Humans; Male; Sex Determination Processes; Sex Differentiation
PubMed: 26950283
DOI: 10.1080/15476278.2016.1145318 -
Clinical Science (London, England :... Jun 2023Reproductive conditions secondary to disorders of the hypothalamic-pituitary-gonadal (HPG) axis are common and are associated with important health implications and... (Review)
Review
Reproductive conditions secondary to disorders of the hypothalamic-pituitary-gonadal (HPG) axis are common and are associated with important health implications and considerable psychosocial impact. Basal and dynamic tests enable interrogation of individual components of the HPG axis, facilitating diagnosis and understanding of the pathophysiology of reproductive disorders. Onset of puberty is controlled by hypothalamic gonadotrophin-releasing hormone (GnRH) neuronal function. To date, a dynamic test of hypothalamic function is not yet available. Therefore, accurate differentiation of pubertal disorders such as constitutional delay of growth and puberty (CDGP) and congenital hypogonadotrophic hypogonadism (CHH) as causes of delayed puberty is challenging due to similar clinical presentations and hormonal profiles. Likewise, although the two commonest reproductive disorders in women, polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhoea (FHA) have disparate hypothalamic function, oligo/amenorrhoea frequently poses a diagnostic conundrum owing to the overlap in the criteria used to define both conditions. This review aims to describe pubertal and reproductive disorders secondary to pathologies affecting the HPG axis. Challenges encountered in clinical practice in differentiating pubertal and reproductive conditions are reviewed in conjunction with the utility of baseline and dynamic endocrine tests to interrogate specific components of the HPG axis. We also highlight putative hypothalamic, pituitary, and gonadal markers in development that could improve the diagnosis of patients presenting with disorders of puberty or reproduction.
Topics: Humans; Female; Amenorrhea; Reproduction; Gonadotropin-Releasing Hormone; Gonads; Hypogonadism
PubMed: 37272254
DOI: 10.1042/CS20220146 -
Problemy Endokrinologii Sep 2021The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex...
The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target indicators of final growth and prevent social deprivation. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of рrecocious puberty, methods of its diagnosis and treatment based on the principles of evidence-based medicine.
Topics: Child; Female; Humans; Male; Puberty; Puberty, Precocious
PubMed: 34766494
DOI: 10.14341/probl12821 -
Endocrine Mar 2021The differential diagnoses of pubertal delay include hypergonadotropic hypogonadism and congenital hypogonadotropic hypogonadism (CHH), as well as constitutional delay... (Review)
Review
The differential diagnoses of pubertal delay include hypergonadotropic hypogonadism and congenital hypogonadotropic hypogonadism (CHH), as well as constitutional delay of growth and puberty (CDGP). Distinguishing between CDGP and CHH may be challenging, and the scientific community has been struggling to develop diagnostic tests that allow an accurate differential diagnosis. Indeed, an adequate and timely management is critical in order to enable optimal clinical and psychosocial outcomes of the different forms of pubertal delays. In this review, we provide an updated insight on the differential diagnoses of pubertal delay, including the available tests, their meanings and accuracy, as well as some clues to effectively orientate towards either constitutional pubertal delay or pathologic CHH and hypergonadotropic hypogonadism.
Topics: Diagnosis, Differential; Expert Testimony; Growth Disorders; Humans; Hypogonadism; Puberty, Delayed
PubMed: 33512657
DOI: 10.1007/s12020-021-02626-z -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Sexual Medicine Reviews Oct 2020Telemedicine (TM) will play a significant role in contemporary practices that diagnose and treat sexual medicine patients. Although only a small percentage of... (Review)
Review
INTRODUCTION
Telemedicine (TM) will play a significant role in contemporary practices that diagnose and treat sexual medicine patients. Although only a small percentage of urologists, sex therapists, social workers, psychiatrists, gynecologists, and urogynecologists currently use TM, many more practices are going to embrace this technology in the near future. This article will discuss the process for implementing TM in sexual medicine with minimal time, energy, effort, and expense. We will also examine compliance and legal issues associated with implementing TM in practice and how to code for TM services based on regulatory guidelines.
OBJECTIVES
The purpose of this article is to improve the understanding of the concept and the trends of using TM to provide care for sexual medicine patients.
METHODS
The study involves a literature review focussing on the new Centers for Medicare and Medicaid Services guidelines including the relaxation of the Health Insurance Portability and Accountability Act requirements.
RESULTS
COVID-19 has changed the doctor-patient relationship especially in the area of sexual medicine. There are many patients with sexual medicine conditions that are amenable to the use of TM methods.
CONCLUSION
Virtual visit utilizing audiovisual telecommunications is a very attractive approach for sexual medicine patients. Many patients with sexual medicine problems are no longer going to accept the antiquated method of healthcare involving making an appointment, visiting a brick-and-mortar facility, and the requirement of having a physical examination. The new normal will be communicating with patients by utilizing TM. Dooley AB, Houssaye N de la, Baum N. Use of Telemedicine for Sexual Medicine Patients. Sex Med Rev 2020;8:507-517.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Female; Female Urogenital Diseases; Gonadal Disorders; Humans; Male; Male Urogenital Diseases; Pandemics; Physician-Patient Relations; Pneumonia, Viral; SARS-CoV-2; Telemedicine
PubMed: 32739238
DOI: 10.1016/j.sxmr.2020.06.001 -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which... (Review)
Review
Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.
Topics: Female; Humans; Male; Anti-Mullerian Hormone; Cryptorchidism; Androgens; Follicle Stimulating Hormone; Peptide Hormones
PubMed: 38501100
DOI: 10.3389/fendo.2024.1361032