Dr Rama Walia, additional professor, Department of Endocrinology, PGIMER, Chandigarh, and her colleagues, who provide outpatient care for a wide range of hormone-related disorders, frequently encounter many children and adolescents struggling with issues related to delayed or early puberty.
In case of delayed puberty, parents are confused and concerned about why their child was not developing “like other children”, with a lack of secondary sexual characteristics. They were also worried about their psychological state of mind, as they feel anxious, withdrawn socially, feeling different from their peers, and awkward.
“This condition is Hypogonadotropic Hypogonadism, where the brain fails to send the correct hormonal signals to the reproductive glands, preventing the initiation or progression of puberty. This failure can be due to a variety of genetic or acquired causes. Genetic causes include mutations in genes responsible for the development and function of the hypothalamus or pituitary gland. Acquired causes may include tumours in the brain region controlling hormone release, infections, injuries, or systemic illnesses that affect overall health and nutrition,” Walia explains.
According to the expert, children with this condition often show no or very delayed development of sexual characteristics, such as testicular enlargement and voice deepening, growth of pubic and underarm hair in boys. “They remain significantly shorter than their peers and may experience low bone density and infertility if not treated. Emotional and psychological impacts are also profound, as children may feel isolated or different, affecting their confidence and social interactions.”
Delayed puberty, Walia adds, is typically defined by the absence of puberty signs in girls by the age of 13 and in boys 14. On the opposite spectrum, early puberty is when it starts before the age eight in girls and nine in boys. The doctor emphasised that parents and teachers should be aware of these age cut-offs and look for signs such as lack of breast growth, absence of menstruation, or no enlargement of testicles and penis by these respective ages.
Similarly, early development of secondary sexual characteristics should not be dismissed as mere “early growth” but taken seriously as a symptom needing medical evaluation.
“There is an urgent need for greater public understanding of such conditions, as early identification and appropriate treatment can completely transform the life trajectory of affected children. Puberty is a natural and important phase in human development that marks the transition from childhood to adulthood.”
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“For children with delayed puberty, the failure to develop normally can lead to physical problems such as stunted growth and osteoporosis due to low hormone levels necessary for bone development. Fertility can also be severely compromised in adulthood. Early puberty has its own set of risks; children who mature too early often stop growing sooner, leading to shorter adult height. Moreover, early exposure to sex hormones may predispose them to metabolic conditions like diabetes and hypertension later in life. Emotional and behavioural issues, including early onset of mood disorders and difficulty adjusting socially, are also frequently documented,” the endocrinologist stresses.
Walia was recently honoured with the Subhash Mukherjee Oration and he delivered a lecture on Hypogonadotropic Hypogonadism. He has published several research articles on this conditions and other related puberty disorders.
Puberty changes are driven by a finely tuned hormonal system controlled by the brain’s hypothalamus and pituitary gland, which communicate with the ovaries or testes to produce the necessary sex hormones like estrogen and testosterone. However, when this complex hormonal signalling system malfunctions, the timing of puberty can be affected in two major ways: it can be significantly delayed, as seen in Hypogonadotropic Hypogonadism, or it can start too early, leading to what is known as precocious or early puberty. Walia highlighted that both delayed and early puberty are not merely variations of normal development but represent underlying medical problems that require timely evaluation and treatment.
With advancements in endocrinology, the outlook for children with these disorders is much improved. Hormone replacement therapy, tailored to each child’s condition, can effectively initiate or regulate puberty, allowing children to develop normally and reach appropriate adult height and sexual maturity.
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For Hypogonadotropic Hypogonadism, therapies may include pulsatile administration of gonadotropin-releasing hormone or direct hormone replacement with testosterone or estrogen. Early puberty can be controlled with medications that suppress premature hormone production, allowing growth to continue until the appropriate age.
“Many don’t know if it is a disease, and it is so easily treatable. Early diagnosis and treatment can lead to excellent long-term physical and psychological outcomes, reducing the risk of complications and improving children’s quality of life dramatically. Parents, teachers, and community members need to be vigilant for warning signs and not ignore delayed or early puberty as just a phase. We must recognise the profound importance of puberty as a window to lifelong health. When puberty is disrupted, the sooner we intervene, the better the outcomes for the child’s body and mind,” Walia suggests.
FSH-stimulated Inhibin B (FSH-iB) test established as a robust marker
The FSH-stimulated Inhibin B (FSH-iB) test has been established as a robust marker for differentiating constitutional delay of puberty from true gonadotropin deficiency, based on work published in the Journal of Clinical Endocrinology and Metabolism (JCEM) by Walia and her colleagues at PGIMER.
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This test, the endocrinologist adds, demonstrated 100 per cent sensitivity and specificity for the prediction of pubertal onset, making it a highly reliable tool for assessing gonadal function in adolescents with delayed puberty. It remains stimulable after FSH administration in individuals with normal puberty but is non-stimulable in patients with Hypogonadotropic Hypogonadism.
Building on this diagnostic foundation, the recent randomised controlled trial published in Endocrine Practice by the same team compared a novel combination therapy regimen — low-dose hCG, FSH, and testosterone (LFT protocol) — against conventional high-dose gonadotropin therapy to induce spermatogenesis and fertility in men with congenital hypogonadotropic hypogonadism. The study found similar rates of successful spermatogenesis between the two protocols and highlighted the clinical utility of monitoring biomarkers such as AMH and inhibin B during treatment. Initiating therapy with FSH and low-dose hCG, titrated to target AMH reduction and normalisation of plasma testosterone, provides a rational and effective strategy for fertility induction in male CHH.
“Together, these studies from PGIMER, demonstrate the power of the FSH-iB test for early diagnosis and the management of delayed puberty disorders. They provide strong evidence supporting the use of biomarker-guided combination therapy for effective treatment and monitoring in patients with hypogonadotropic hypogonadism,” Walia concludes.
