When Lifelong Anosmia Reveals Hypogonadism: A Case of Kallmann Syndrome with Primary Amenorrhea

Kallmann syndrome (KS) is a rare genetic disorder characterized by hypogonadotropic hypogonadism and anosmia. It is often underdiagnosed in females due to subtle clinical presentation. This can lead to delays in accurate diagnosis and proper long-term management, particularly in women presenting with amenorrhea and uterine hypoplasia.

A 25-year-old nulligravid woman presented with lifelong absence of spontaneous menstruation, anosmia, and partial pubertal development. She was initially misdiagnosed with secondary amenorrhea after a positive progesterone withdrawal test, but later recognized as having primary amenorrhea. Examination revealed Tanner stage M3P3, uterine and ovarian hypoplasia on transvaginal ultrasonography, low estradiol with suppressed gonadotropins, normal 46,XX karyotype, and bilateral absence of the olfactory bulbs on brain MRI, confirming Kallmann syndrome. Dual-energy X-ray absorptiometry demonstrated reduced bone mass consistent with chronic hypoestrogenism. She was started on combined estrogen-progestin therapy with calcium and vitamin D supplementation for estrogen priming and bone protection, with fertility-oriented management and baseline psychological screening integrated into care.

This case illustrates the diagnostic challenges of Kallmann syndrome in women with partial pubertal development. Insufficient estrogen exposure may allow secondary sexual characteristic development while failing to achieve uterine maturation and spontaneous menstruation. Chronic hypoestrogenism contributes not only to reproductive tract hypoplasia but also poses long-term risks to bone, cardiovascular, metabolic, and mental health, underscoring the importance of comprehensive evaluation and management.

Kallmann Syndrome should be suspected in any female patient with hypogonadotropic hypogonadism and anosmia. Withdrawal bleeding should not be mistaken for true menarche, as this may obscure the diagnosis. Early diagnosis is essential to optimize hormonal replacement, preserve fertility potential, and improve long-term systemic health outcomes.