Microphallus early management in infancy saves adulthood sensual life: A comprehensive review.

Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected individuals. This article comprehensively reviews micropenis, its etiology, epidemiology, and various treatment options. We conducted a thorough literature review to collect relevant information on micropenis and microphallus, as well as related disorders. Our primary databases were PubMed, Medline, and Google Scholar. We searched for articles published in English between 2000 and 2023. Our analysis included 67 review articles, 56 research studies, 11 case reports, one guideline, and one editorial. Our search terms included "microphallus", "micropenis", "congenital hypogonadotropic hypogonadism", "androgen insensitivity syndrome", "pediatric management of micropenis", "testosterone therapy", and "psychosocial implications of micropenis". We focused on diagnosing micropenis and related conditions, including hormonal assessments, medical and surgical treatment options, psychosocial and psychological well-being, sexual development of adolescents, and sociocultural influences on men's perceptions of penile size. Additionally, we explored parenting and family dynamics in cases of micropenis and disorders of sex development, implications of hormonal treatment in neonates, and studies related to penile augmentation procedures and their effectiveness. The article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with micropenis. Surgical procedures, such as penile lengthening and girth enhancement, and non-surgical approaches like hormonal therapy are explored. The significance of psychological support, education, and lifestyle modifications is emphasized. Early management and comprehensive care are crucial for individuals with micropenis, from infancy to adolescence and beyond. A multidisciplinary approach involving urologists, endocrinologists, and mental health professionals is recommended. Regular assessment of treatment effectiveness and the need for updated guidelines are essential to provide the best possible care. Healthcare professionals should prioritize early diagnosis, and neonatologists should measure stretched penile length in neonates. A collaborative effort is needed among professionals, parents, and affected individuals to create a supportive environment that recognizes worth beyond physical differences. Continuous research and evidence-based updates are crucial for improving care standards.

Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement.

There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second-termed "mini-puberty"-in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications.

Novel Finding of Micropenis Caused by Mutation of the ADGRG2 Gene: A Case Report and Literature Review.

BACKGROUND: This study reported a case of micropenis caused by a novel hemizygous mutation in the ADGRG2 gene, which aimed to expand the understanding of sexual dysplasia caused by ADGRG2 gene mutation. CASE PRESENTATION: We present the clinical data and genetic test results of a patient with micropenis admitted in September, 2022, to the Tongji Hospital. The patient was a 9-year-10- month-old male whose chief complaint was the presence of a short penis over a period of three years. In April 2016, the patient underwent corrective surgery for a clubbed penis. Upon admission to the study hospital, his height and weight were 145.0 cm (75-90th percentile) and 37.8 kg (50-75th percentile), respectively, and his BA was 12 years old. His physical characteristics included a normal face, bilateral testicle size of 2 ml, and penile length of about 3 cm. A gonadotrophin-releasing hormone-stimulating test revealed normal hypothalamic-pituitary-gonadal axis function. An HCG stimulation test indicated normal sperm production in the testis. Key abnormalities from auxiliary examinations included low testosterone and high ACTH, dehydroepiandrosterone sulfate, androstenedione, and 17-OH-P levels. Genetic testing revealed a new hemizygous mutation, a splicing mutation in intron 4 of the ADGRG2 gene (ChrX: 19040187 (NM_001079858.3): c.154 + 2T > A, inherited from the mother. CONCLUSION: This study reported a case of micropenis caused by a new hemizygous mutation in the ADGRG2 gene. This indicates the importance of genetic testing and gene-guided treatments to improve prognosis.

Efficacy of Transdermal Dihydrotestosterone and Testosterone Enanthate for Penile Augmentation in Patients With Idiopathic Micropenis: A Comparative Randomized Study.

Objectives: Our study aimed to compare the efficacy of transdermal dihydrotestosterone and testosterone enanthate in treating idiopathic micropenis. Patients and methods: It's a comparative randomized study of 49 patients with idiopathic micropenis who are followed up in the Endocrinology-Diabetology and Nutrition Department of Mohammed VI University Hospital Center of Oujda, Morocco. The study was conducted from December 2019 to April 2021. All patients received a clinical examination including measurement of penis size before and after hormonal treatment. The patients were divided into two random groups, each group received a different drug, the first arm was treated with transdermal dihydrotestosterone (27 patients) and the second arm was treated with testosterone enanthate (22 patients). The Trial registration number was researchregistry7745. Results: The majority of the patients were children. The mean age was 9.7 ± 4.4 years. In the first arm, the mean penile size increased from -2.42 SD to -0.7 SD with a gain of 2.37 cm on average. In the second arm, the mean size increased from -2.48 SD to -0.69 SD, with a gain of 1.82 cm on average. The increase in penile size in the first arm was significantly greater than in the second arm (P = .008). No side effects were detected in both arms. Discussion and conclusion: In the present study, we demonstrated the superiority of transdermal DHT compared to injectable exogenous testosterone in the treatment of idiopathic micropenis. According to the age subgroups, there was no significant difference between the 2 treatments in each age group.

Pontocerebellar Hypoplasia 7 with Novel Compound Heterozygous Variants of TOE1 in a Boy with Micropenis, Developmental Delay, and Ataxia: The First Korean Case Report.

Pontocerebellar hypoplasia (PCH) is a rare neurodegenerative disorder characterized by hypoplasia of the pons and cerebellum and global developmental delay. Among several PCH types, PCH7 is a characteristic type that manifests with not only brain lesions but also sexual developmental disorders. The causative gene, TOE1, encodes a protein involved in small ribonucleic acid maturation and processing. TOE1 mutation is associated with neuronal survival that causes hypoplasia of the cerebellum and pons. We report the case of a male patient with PCH7, developmental delay, ataxia, micropenis, and undescended testis. Genetic analysis revealed compound heterozygous missense variants (c.955C>T and c.533T>G) in the TOE1 gene.

Buried Penis: A Rare Cause of Lower Urinary Tract Symptoms in the Pediatric Population.

A buried penis is a probably underdiagnosed entity. It is defined as a penis of normal size that appears to be smaller than expected due to concealment within the pubic tissue. This case report explores the presentation of a 12-month-old male infant with exuberant ballooning of the prepuce during micturition, requiring manual expression of urine for the duration of two months prior to presentation. The penis was not visible above the skin level, with only the glands covered by prepuce protruding. However, the penis could be exposed when holding the base of the penis, revealing a regular-sized penis. The clinical diagnosis of a buried penis with megaprepuce was assumed, and the patient was referred to the pediatric surgery department for further management. Corrective surgery was performed nine months later with excellent cosmetic and functional results. The buried penis has a typical appearance with a partially visible or completely invisible penis, with only the glans covered by prepuce protruding, and it can be completely asymptomatic or cause micturition difficulties, sexual dysfunction, and recurrent urinary tract infections or balanitis. The diagnosis is clinical and the treatment is surgical, although the surgical approach is controversial.

A Rare Case of Precocious Puberty in a Child with a Novel GATA-4 Gene Mutation: Implications for Disorders of Sex Development (DSD) and Review of the Literature.

BACKGROUND: Disorders/Differences of sex development (DSD) are often due to disruptions of the genetic programs that regulate gonad development. The GATA-4 gene, located on chromosome 8p23.1, encodes GATA-binding protein 4 (GATA-4), a transcription factor that is essential for cardiac and gonadal development and sexual differentiation. CASE DESCRIPTION: A child with a history of micropenis and cryptorchidism. At 8 years of age, he came under our observation for an increase in sexual pubic hair (pubarche). The laboratory parameters and the GnRH test suggested a central precocious puberty (CPP). Treatment with GnRH analogs was started, and we decided to perform genetic tests for DSD. The NGS genetic investigation showed a novel and heterozygous variant in the GATA-4 gene. DISCUSSION: In the literature, 26 cases with 46,XY DSD due to the GATA4 gene were reported. CONCLUSION: The novel variant in the GATA-4 gene of our patient was not previously associated with DSD. This is the first case of a DSD due to a GATA-4 mutation that develops precocious puberty. Precocious puberty could be associated with DSD and considered a prelude to hypogonadism in some cases.

Penile Length Assessment of Children Treated for Primary Buried Penis: Can Satisfying Penile Growth Always Be Achieved?

Primary buried (BP) penis is describes as a small penis caused by a penile ligaments anomaly; it is unclear if a primary BP could reach a normal length. We selected 49 patients treated at our institution between 2015 and 2020 in order to post-operatively evaluate the SPL after one year. SPL was evaluated according to the PH Tanner staging system for pre-pubertal patients according to age-normalized values. A micropenis was detected if the SPL was below 2.5 SD. A normal SPL was found in thirty-two patients, eighteen were in PH Stage 1, four were in PH Stage 2, six were in PH Stage 3, and four were in PH Stage 5. Seventeen patients showed a reduced SPL; in seven of these (four in PH Stage 4 and three in PH Stage 5), their SPL was <2.5 ST. The difference in micropenis prevalence between the pre-pubertal and post-pubertal patients was significant (p = 0.038). A primary BP grows normally during the pre-pubertal period, where patients frequently showed a normal SPL, but it seems to be unable to reach a normal length in the higher PH stages, where the SPL is used to detect a micropenis. We suggest that a primary BP should be considered not as a simple defect of the penile ligaments and surrounding tissues, but as an incomplete manifestation of a micropenis due to a growth slowdown of the organ in late puberty.

Estimation of Reference Values for External Genitalia Parameters in North Indian Preterm and Term Male Newborns.

OBJECTIVES: To generate gestation-wise normative data of external genitalia measurements in North Indian term and preterm male newborns. METHODS: This was a hospital-based cross-sectional observational study. Male neonates born between 28-42 wk of gestation (at 24-72 h of life) were consecutively recruited in the study. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Stretched penile length (SPL), penile width (PW), upper anogenital distance (AGDu), lower anogenital distance (AGDl) and anogenital ratio (AGR)]. RESULTS: Out of 532 newborns, 208 (39.1%) were preterm. Mean (± SD) SPL and PW were 27.9 ± 3.6 mm and 10.6 ± 1.3 mm respectively. The mean values for AGDl, AGDu and AGR were 20.13 ± 4.04 mm, 39.2 ± 5.59 mm, and 0.51 ± 0.07, respectively. SPL less than 21 mm in a term male newborn and 17.5 mm in preterm should be considered micropenis (<2.5 SD) in our population. Gestation-wise percentile charts for SPL, PW, AGDl, AGDu and AGR were generated. CONCLUSIONS: The reference values and percentile charts generated can serve as local normative data for accurate interpretation of genital measurements in North Indian newborns, assessment of ambiguous genitalia and avoiding diagnostic errors.

Micropenis.

Micropenis, i.e., a structurally normal but abnormally small penis is defined as stretched penile length (SPL) 2.5 SD below the mean for age and sexual stage. Several studies worldwide have published country-specific normative data on SPL; an appropriate cutoff for evaluation of micropenis as per international standards would be below 2 cm at birth and below 4 cm after 5 y of age. Testosterone production by fetal testes, its conversion to dihydrotestosterone (DHT) and its action on the androgen receptor is necessary for normal penile development. Hypothalamo-pituitary disorders (gonadotropin or growth hormone deficiencies), genetic syndromes, partial gonadal dysgenesis, testicular regression, disorders of testosterone biosynthesis and action constitute the various etiologies of micropenis. Associated hypospadias, incomplete scrotal fusion, and cryptorchidism are suggestive of disorders of sex development (DSD). Along with basal and human chorionic gonadotropins (HCG)-stimulated gonadotropins, testosterone, DHT, and androstenedione levels, karyotype assessment is equally important. Treatment aims at attaining penile length sufficient enough for urination and to perform sexual function. Hormonal therapy with intramuscular or topical testosterone, topical DHT or recombinant follicle stimulating hormone (FSH) and luteinizing hormone (LH) should be attempted in the neonatal or infancy period. The role of surgery for micropenis is limited and has variable patient satisfaction and complication outcomes. There is a need for long-term studies on the adult SPL achieved following treatment for micropenis in infancy and childhood.

Imaging in fetal genital anomalies.

Genital anomalies are a heterogeneous group of congenital pathologies that have become increasingly relevant since the Chicago Consensus of 2005. Their postnatal diagnosis has developed significantly in the last two decades, while prenatal diagnosis seems to be underdeveloped, with few protocols available, fragmented scientific literature, and low diagnostic rates. This review aims to examine the current status of this subspecialty from the perspective of prenatal imaging. Indications for the evaluation of fetal genitalia can be divided into medical and non-medical reasons. Medical reasons include sex-linked disorders, detection of other anomalies, relevant family history, or multiple pregnancy. Non-medical reasons include parental request for sex disclosure. Disclosure of fetal sex may be associated with ethical, legal, and medical issues. The main imaging technology used is 2D ultrasound, although there are other complementary techniques such as 3D, MRI, or Color Doppler. Regarding working methodology, several authors have drawn attention to the lack of standardized protocols and guidelines. Most guidelines tend to limit their recommendations to study indications and ethical issues. Technical proposals, measurements, or working methods have not yet been standardized. Fetal sex determination is usually divided into early and late gestation. Early gestation is based on the sagittal sign. Late gestation is based on direct visualization. There are several measurements to describe male and female genitalia, such as penile length, bilabial diameter, or scrotal diameter. Prenatal diagnosis of genital pathologies presents some particularities such as the wide spectrum of phenotypes, the high frequency of associated deformities, or the time of diagnosis. Some of the most frequent pathologies are ambiguous genitalia, fetal sex discordance, hypospadias, micropenis, clitoromegaly, ovarian cysts, hydro(metro)colpos, and cloacal anomalies. Higher-quality studies and direction from scientific societies through the implementation of clinical guidelines are needed.

Longitudinal clinical course in patients with 5α-reductase type 2 deficiency treated with testosterone and dihydrotestosterone during infancy and puberty.

5α-reductase type 2 (5αRD2) deficiency is a 46,XY disorder of sex development caused by impaired conversion of testosterone (T) to dihydrotestosterone (DHT). Penile enlargement therapy is important for male patients with 46,XY 5αRD2 deficiency who have undermasculinized external genitalia, such as severe micropenis. High-dose T and percutaneous DHT replacement are reportedly efficacious for penile enlargement in patients with this disorder. We presented herein the longitudinal course of four patients with 46,XY 5αRD2 deficiency who received T and DHT. T replacement therapy during infancy increased the stretched penile length (SPL) in three of the patients but was ineffective in one patient. DHT was administered to the three patients after T replacement therapy and further increased the SPL. During and after puberty, two patients asked for and received T replacement therapy, which contributed to increasing their SPL. A semen test in one patient with T replacement therapy at age 27 years revealed cryptozoospermia despite normal testicular volume. The clinical course of our patients during infancy indicated that DHT therapy may be preferrable to T replacement therapy for penile enlargement in patients with 5αRD2 deficiency. During and after puberty, T replacement therapy promoted penile enlargement possibly because of increased conversion of T to DHT via increased 5α-reductase type 1 activity even in patients in whom it was ineffective during infancy. In conclusion, DHT is effective for penile enlargement during infancy in patients with 5αRD2 deficiency while T replacement therapy is a viable option during puberty.

Analysis of the efficacy of negative pressure suction and topical testosterone cream in the treatment of simple micropenis in school-aged obese children / 现代泌尿外科杂志

【Objective】 To investigate the efficacy of negative pressure suction and topical testosterone cream in the treatment of simple micropenis in school-aged obese children and the effects on blood lipids and serum sex hormones. 【Methods】 A total of 79 children aged 7 to 14 (10.50±1.62) years treated and followed up during Nov.2020 and Jul.2022 were involved. The patients were randomly enrolled in the negative pressure suction group (n=39) and the topical testosterone cream group (n=40). The negative pressure suction group was treated with negative pressure suction for 30 min/time, 1 time/day, for 30 d. The topical testosterone cream group was treated with topical testosterone cream applied to the scrotum of the penis 2 times/day for 30d. The transverse and longitudinal diameter of the glans, penile flaccidity, retraction length, serum sex hormones and blood lipids were measured before and after treatment. 【Results】 In both groups, penile flaccidity, retracted length and transverse and longitudinal diameter of the glans were significantly greater at 30 days of treatment and 2 months of follow-up than those before treatment (P0.025). In the topical testosterone cream group, at 30 days of treatment, there were significant differences in serum total cholesterol (CHOL), apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), high-density lipoprotein (HDL), low-density lipoprotein (LDL), sex hormone binding protein (SBG), estradiol (E2) and testosterone (TES) compared to those before treatment; at 2 months of follow-up, the differences in Apo A1, HDL, TES and DHS were still significant (P<0.025). 【Conclusion】 Both topical testosterone cream and negative pressure suction have significant efficacy in the treatment of micropenis in school-aged obese children, while topical testosterone cream has some side effects and retraction may occur after treatment. Negative pressure suction is safe and easy to operate, without side effects and retraction, and can be promoted for the treatment of micropenis in obese children.

A Korean male with Kleefstra syndrome presented with micropenis.

Kleefstra syndrome is caused by chromosome 9q34.3 deletion or heterozygous mutations in the euchromatin histone methyl transferase 1 (EHMT1) gene. It can be accompanied by intellectual disability, distinctive facial features, microcephaly, psychiatric disorders, hypotonia in childhood, hearing loss, heart defects, renal defects, epilepsy, speech anomalies, and obesity. Furthermore, genital anomalies are present in 30%-40% of male patients with Kleefstra syndrome, but their mechanisms have not been elucidated. Herein, we report a patient with Kleefstra syndrome presenting with micropenis. The patient was transferred to Kyungpook National University Children's Hospital for management of imperforate anus on the day of birth. Physical examination revealed micropenis with stretched penile length of 0.9 cm and facial dysmorphisms, including hypertelorism and anteverted nares. Chromosomal microarray revealed 424-kb heterozygous deletion at chromosome 9q34.3 (arr[hg19] 9q34.3 (140,234,315-140,659,055)x1). Among the involved main OMIM genes, phenotypically relevant genes were EHMT1 and NSMF. Endocrinological investigation showed low basal gonadotropin and testosterone levels. Anterior pituitary hormones and steroid hormone levels were in the normal range. Testicular function was normal based on human chorionic gonadotropin stimulation test. The patient experienced improvement in penile length growth with intramuscular testosterone enanthate injection initiated at 4 months of age. The purpose of this study is to describe the etiology, endocrine laboratory tests, and treatment of micropenis in Kleefstra syndrome.

Are androstenedione, dihydrotestosterone, thyroid-stimulating hormone, insulin-like growth factor I, and insulin-like growth factor binding protein 3 necessary for isolated micropenis healthy boys' evaluation without any phenotypic abnormalities? A cross-sectional study.

The study aimed to familiarise primary care physicians and specialists with the minimum hormonal diagnostic tests necessary to assay isolated micropenis in healthy children without any phenotypic abnormality. Children aged 6-15 years (mean 11.6 ± 1.68) were assessed from May 2010 to September 2021 (N = 247). Multiple regression analysis showed correlations between stretched penile length (SPL) and hormonal assays as follows: follicle-stimulating hormone (FSH): r = 0.097, p = 0.035; luteinizing hormone (LH): r = 0.139, p = 0.012, thyroid-stimulating hormone (TSH): r = -0.001, p = 0.321; testosterone (T): r = 0.118, p = 0.004; dihydrotestosterone (DHT): r = 0.002, p = 0.243; androstenedione (Δ4And): r = -0.004, p = 0.502; insulin-like growth factor I (IGF-I): r = -0.003, p = 0.062; and IFG-binding protein 3 (IGF-BP3 ): r = 0.052, p = 0.051. The most hormonal disorder was testosterone deficiency. TSH, Δ4And, and DHT were normal in all boys. SPL was significantly correlated with FSH, LH, and T, but there was no significant correlation between SPL and TSH, DHT, Δ4And, IGF-I, and IGF-BP3 . Whenever the isolated micropenis is seen without other anomalies, it is sufficient to assay testosterone, FSH, and LH in the first step.

Dilemma on Indonesian adult with micropenis during COVID-19 pandemic: A case report and review article.

Background: Micropenis usually has a series of causative factors that must be identified to determine the treatment modality. Case presentation: A 24-years-old Indonesian male complained of a small penis since infancy. The patient has a short penis size (3 cm), no pubic hair, small scrotum, both testes cannot hide palpable, and tanner scale 2. The hormonal examination includes testosterone hormone of 14.94 ng/dL, luteinizing hormone of 14.89 mUI/mL, and follicle-stimulating hormone of 67.51 mUI/mL. Ultrasound showed no testicular location and only a prostate-like appearance of a size of 0.6 × 2.07 cm on the abdomen. The patient will receive therapy but was constrained by the COVID-19 pandemic. Discussion: diagnosis of micropenis and gonadotropin hormone disorders must be detected early and receive treatment immediately for better results. Conclusion: Micropenis is a medical diagnosis that depends on proper examination and management, and early diagnosis is essential to improve prognosis.

A Novel Heterozygous Mutation of the CYP17A1 Gene in a Child with a Micropenis and Isolated 17,20-Lyase Deficiency.

Disorders of sexual development (DSDs) are characterized by a heterogeneous group of congenital conditions associated with atypical development of the sex chromosomes, gonadal or anatomical sex. We report the case of a child with an isolated micropenis, a typical feature of the 46,XY DSD showing low basal testosterone levels and post-stimulation with the hCG test. Molecular analysis using a next-generation sequencing (NGS) panel of 50 genes involved in DSDs was performed, revealing a heterozygous mutation, c.1040G > ANM_000102.4, in the CYP17A1 gene. Sanger sequencing was used to confirm the gene variant detected by NGS; it was also performed to his parents, revealing the presence of the same mutation in the mother, who presented no features of the disease. Then, the serum steroid profile was determined by liquid chromatography coupled to tandem mass spectrometry analysis. Interestingly, this analysis highlighted low levels of testosterone, progesterone, and dehydroepiandrostenedione, as also confirmed by a stimulus test with ACTH. These results suggest that, in some cases, heterozygous mutations in recessive genes involved in adrenal steroidogenesis can also affect the patient's phenotype.

Reference penile size measurement and correlation with other anthropometric dimensions: a prospective study in 800 men.

Virility and sexual pleasure have long been associated with penile size and this, in turn, has typically been linked to some anthropometric measurements, such as foot size or height, leading to various misconceptions from both men and women. Our intention is to estimate penile size parameters in Argentina and evaluate the correlation between penile size and certain anthropometric measurements. This is a cross-sectional, descriptive, multicenter, and observational study. Male patients who underwent a urological procedure were included in four hospitals located in different regions of the country. Different anthropometric measurements were obtained: height, weight, penile circumference, flaccid and stretched length, and foot length. A total of 800 patients were evaluated. Mean left foot was 26.4 cm. Mean flaccid penile length was 11.4 (95% confidence interval [CI]: 8-14) cm, and mean penile circumference was 10.1 (95% CI: 8-12) cm. Finally, mean stretched penis was 15.2 (95% CI: 11-18.5) cm. We can confirm that estimates of the average penile measurements in Argentina are flaccid penis length of 11.4 cm, penile circumference of 10.1 cm, and stretching the penis to the maximum in flaccidity of 15.2 cm. Correlations between flaccid penis length, stretched out, penile circumference, height, weight, and length of the left foot were evaluated, finding low or no correlation between those mentioned, except for flaccid and stretched length.

Current concepts surrounding neonatal hormone therapy for boys with congenital hypogonadotropic hypogonadism.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) is a genetic disorder of reproduction and development, characterized by deficient gonadotropin-releasing hormone (GnRH) secretion or action, affecting 1-in-4,000-15,000 males. Micropenis and undescended testes are cardinal features of antenatal GnRH deficiency and could indicate absent minipuberty in the first postnatal months. In this review, we outline the pathophysiology and clinical consequences of absent minipuberty and its implications for optimal approaches to the endocrine management of affected boys. AREAS COVERED: Deficient GnRH activity during fetal development and neonatal-infancy phase of minipuberty accounts for the diminished mass of Sertoli cells and seminiferous tubules among CHH males, enduring impairment of reproductive function even during gonadotropin replacement in adult life. In overcoming this obstacle, several clinical studies of neonatal gonadotropin replacement have consistently shown positive results in inducing testicular development and correcting cryptorchidism. EXPERT OPINION: A high index of clinical suspicion, combined with hormonal testing undertaken in the postnatal period of 1-4 months, can reliably confirm or refute the diagnosis of CHH. Timely identification of CHH in affected male infants (having characteristic "red flag' developmental anomalies) opens up the possibility for gonadotropin replacement as a targeted therapy to restore the normal hormonal milieu of minipuberty. Further work is necessary in formulating optimal gonadotropin treatment regimens to be more widely adopted in clinical practice.

Recent advancement in the treatment of boys and adolescents with hypogonadism.

Clinical manifestations and the need for treatment varies according to age in males with hypogonadism. Early foetal-onset hypogonadism results in disorders of sex development (DSD) presenting with undervirilised genitalia whereas hypogonadism established later in foetal life presents with micropenis, cryptorchidism and/or micro-orchidism. After the period of neonatal activation of the gonadal axis has waned, the diagnosis of hypogonadism is challenging because androgen deficiency is not apparent until the age of puberty. Then, the differential diagnosis between constitutional delay of puberty and central hypogonadism may be difficult. During infancy and childhood, treatment is usually sought because of micropenis and/or cryptorchidism, whereas lack of pubertal development and relative short stature are the main complaints in teenagers. Testosterone therapy has been the standard, although off-label, in the vast majority of cases. However, more recently alternative therapies have been tested: aromatase inhibitors to induce the hypothalamic-pituitary-testicular axis in boys with constitutional delay of puberty and replacement with GnRH or gonadotrophins in those with central hypogonadism. Furthermore, follicle-stimulating hormone (FSH) priming prior to hCG or luteinizing hormone (LH) treatment seems effective to induce an enhanced testicular enlargement. Although the rationale for gonadotrophin or GnRH treatment is based on mimicking normal physiology, long-term results are still needed to assess their impact on adult fertility.