Introduction
Reproductive endocrinology in children involves the study of the development, function, and disorders of the hypothalamic–pituitary–gonadal (HPG) axis. Unlike adults, in whom the system operates cyclically or continuously, the paediatric HPG axis undergoes distinct phases of activation and quiescence from fetal life through puberty.
Reproductive disorders in children manifest as abnormalities in sexual differentiation, pubertal timing, gonadal development, or fertility. These conditions often present with clinical signs such as ambiguous genitalia, delayed or precocious puberty, or menstrual irregularities in adolescents.
In Ghana and sub-Saharan Africa, limited access to endocrine diagnostic testing, late presentation, and sociocultural sensitivities surrounding reproductive development pose additional challenges. Hence, an understanding of normal reproductive physiology and early recognition of pathological patterns is crucial for paediatricians.
Physiology of the Hypothalamic–Pituitary–Gonadal Axis
The HPG axis controls reproductive development and function through the coordinated actions of:
- Hypothalamus: Secretes gonadotropin-releasing hormone (GnRH) in a pulsatile fashion.
- Pituitary gland: Responds to GnRH by releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
- Gonads (testes and ovaries): Produce sex steroids (testosterone, estrogen, progesterone) and gametes in response to LH and FSH.
Phases of Activity
- Fetal life: HPG axis active; sex differentiation occurs.
- Mini-puberty (first 6 months postnatal): Temporary activation, useful for early diagnosis of some disorders.
- Childhood: Relative quiescence of the axis.
- Puberty: Reactivation leading to secondary sexual characteristics and fertility.
Classification of Paediatric Reproductive Disorders
Reproductive disorders can be broadly grouped into:
- Disorders of Sexual Differentiation (DSD)
- Pubertal Disorders
- Gonadal Dysfunction
- Menstrual and Fertility Disorders
Each category encompasses multiple aetiologies, with some overlap.
Disorders of Sexual Differentiation (DSD)
These are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical.
Classification
- 46,XX DSD: Often due to exposure to excess androgens (e.g., congenital adrenal hyperplasia).
- 46,XY DSD: Results from under-virilization due to gonadal dysgenesis or androgen insensitivity.
- Sex Chromosome DSD: Such as Turner syndrome (45,X) and Klinefelter syndrome (47,XXY).
Clinical Presentation
- Ambiguous genitalia at birth
- Inguinal or labial masses (testes)
- Discordance between genetic and phenotypic sex
- Failure of virilization in adolescence
Diagnosis
- Karyotyping: Determines chromosomal sex.
- Hormonal assays: Measure 17-hydroxyprogesterone, testosterone, LH, FSH, and AMH.
- Pelvic ultrasound: Evaluates internal genital structures.
- Genetic testing: Useful where available.
Local Context
In Ghana, many cases of ambiguous genitalia present late due to cultural stigma and inadequate neonatal screening. Early multidisciplinary assessment (paediatrician, endocrinologist, surgeon, psychologist) is critical for optimal outcomes and family counselling.
Management
- Gender assignment based on diagnostic clarity and cultural sensitivity.
- Surgical correction where indicated.
- Hormone replacement (e.g., glucocorticoids in CAH).
- Psychosocial support for the patient and family.
Disorders of Puberty
Definition
Puberty is the process leading to sexual maturation and reproductive capability. It involves the activation of the HPG axis.
- Precocious puberty: Onset of secondary sexual characteristics before age 8 in girls or 9 in boys.
- Delayed puberty: Absence of such characteristics by age 13 in girls or 14 in boys.
Precocious Puberty
Types
- Central (GnRH-dependent): Premature activation of the HPG axis.
- Peripheral (GnRH-independent): Due to excess sex steroids from gonadal, adrenal, or ectopic sources.
Causes
- Central: Idiopathic (especially in girls), CNS lesions (e.g., hypothalamic hamartoma), CNS infections (common post-meningitic sequelae in sub-Saharan Africa).
- Peripheral: Congenital adrenal hyperplasia, ovarian cysts or tumours, McCune-Albright syndrome, exogenous hormones.
Clinical Features
- Early breast development (thelarche), pubic hair (pubarche), or menses in girls.
- Testicular enlargement, penile growth, or voice deepening in boys.
- Advanced bone age and accelerated growth.
Investigations
- LH and FSH (basal and GnRH-stimulated).
- Sex steroids (estradiol, testosterone).
- Bone age (left hand/wrist X-ray).
- MRI brain for CNS pathology.
Management
- Central: GnRH analogues to suppress premature axis activation.
- Peripheral: Treat underlying cause (e.g., tumour resection, corticosteroid replacement in CAH).
- Psychological support: Essential in early-developing children in conservative societies.
Delayed Puberty
Causes
- Constitutional delay: Most common; familial and benign.
- Hypogonadotropic hypogonadism: Due to pituitary/hypothalamic defects (e.g., Kallmann syndrome, chronic malnutrition).
- Hypergonadotropic hypogonadism: Primary gonadal failure (e.g., Turner, Klinefelter, mumps orchitis).
Clinical Features
- Absence of breast or testicular development.
- Short stature or growth failure.
- Psychosocial distress among peers.
Investigations
- LH, FSH, and sex steroid levels.
- Karyotype where indicated.
- MRI for central lesions.
- Bone age assessment.
Management
- Observation in constitutional delay.
- Hormone replacement therapy (estrogen or testosterone).
- Treat underlying systemic or nutritional disorders.
Ghanaian Context
Malnutrition, chronic infections, and delayed recognition of hypogonadism remain frequent contributors to delayed puberty. Clinical suspicion and affordable initial hormonal testing are essential in regional hospitals.
Gonadal Dysfunction
Primary Gonadal Failure
Results from intrinsic gonadal abnormalities leading to hypergonadotropic hypogonadism.
Common causes include:
- Turner syndrome (45,X)
- Klinefelter syndrome (47,XXY)
- Chemotherapy or radiotherapy-induced damage
- Autoimmune oophoritis or orchitis
Clinical Features
- Absent or incomplete pubertal development
- Infertility
- Amenorrhea in females
- Small, firm testes in males
Management
- Hormone replacement therapy (HRT) for puberty induction and maintenance.
- Fertility counselling.
- Monitor for associated comorbidities (e.g., cardiovascular risk in Turner syndrome).
Secondary Gonadal Failure
Due to hypothalamic or pituitary defects causing hypogonadotropic hypogonadism.
Causes: CNS tumours, trauma, chronic systemic illness, or genetic syndromes like Prader-Willi.
Menstrual and Fertility Disorders
Although more relevant in late adolescence, early recognition of abnormal menstrual patterns is important.
#A# Common Disorders - Primary amenorrhea: No menses by age 15 or within 3 years of thelarche.
- Secondary amenorrhea: Absence of menses for >3 months in a previously menstruating girl.
- Oligomenorrhea: Infrequent menses (>35 days apart).
#A# Causes - Anatomic (imperforate hymen, Müllerian agenesis)
- Ovarian (PCOS, gonadal dysgenesis)
- Pituitary (hyperprolactinaemia)
- Hypothalamic (stress, undernutrition, excessive exercise)
Investigations
- Serum LH, FSH, prolactin, TSH, estradiol.
- Pelvic ultrasound.
- Progesterone challenge test.
Management
- Treat underlying cause (e.g., surgical correction, nutritional rehabilitation).
- Hormonal therapy for regulation.
- Psychological counselling.
Approach to a Child with a Reproductive Disorder
- Detailed history
- Onset and progression of puberty
- Family history of delayed or precocious puberty
- Neonatal genital appearance, chronic illnesses
- Drug and toxin exposure
- Physical examination
- Tanner staging
- Height, weight, and growth velocity
- Dysmorphic features or signs of chronic disease
- Laboratory evaluation
- Hormonal profile (LH, FSH, estradiol/testosterone, prolactin, TSH)
- Karyotyping where indicated
- Imaging
- Pelvic/abdominal ultrasound
- MRI brain/pituitary for central causes
- Psychosocial assessment
- Critical in addressing stigma and self-image concerns, particularly in the Ghanaian context.
Challenges in the Ghanaian and Sub-Saharan Context
- Limited endocrine testing: Many hospitals lack the capacity for detailed hormonal assays.
- Late presentation: Families may delay seeking medical advice due to cultural stigma.
- Cost barriers: HRT and genetic testing may be unaffordable for many patients.
- Need for multidisciplinary care: Involving paediatric endocrinologists, surgeons, psychologists, and social workers.
- Education and awareness: Community sensitization and training of primary care workers are key.
Key Takeaways
- Reproductive disorders in children arise from dysfunction of the HPG axis or abnormalities in sexual differentiation.
- Early recognition and hormonal evaluation are crucial to prevent long-term physical and psychosocial complications.
- In Ghana, limited diagnostic resources demand pragmatic, symptom-based approaches supplemented by clinical acumen.
- Psychosocial support and culturally sensitive counselling are integral to care.
Further Reading
- Brook CGD, Clayton PE, Brown RS. Brook’s Clinical Pediatric Endocrinology, 8th ed. Wiley-Blackwell, 2023.
- Sperling MA. Pediatric Endocrinology, 5th ed. Elsevier, 2021.
- Osei K, et al. “Paediatric endocrine practice in sub-Saharan Africa: challenges and opportunities.” J Clin Res Pediatr Endocrinol, 2019.
- WHO. Sexual Maturation and Pubertal Disorders: A Guide for Primary Health Care Providers, Geneva, 2018.
- West African College of Physicians (WACP) Curriculum for Paediatric Endocrinology, 2024.