Hypogonadism

Hypogonadism refers to insufficient gonadal function resulting in inadequate sex hormone production and/or impaired gamete production. Primary hypogonadism (hypergonadotropic): gonadal failure with elevated FSH/LH (loss of negative feedback). Causes: Klinefelter syndrome (47,XXY — most common genetic cause in males), Turner syndrome (45,X — females), gonadal dysgenesis, bilateral orchiectomy, chemotherapy/radiation-induced gonadal damage, autoimmune oophoritis/orchitis, premature ovarian insufficiency (POI). Secondary hypogonadism (hypogonadotropic): hypothalamic-pituitary dysfunction with low/inappropriately normal FSH/LH. Causes: pituitary tumors (prolactinoma most common), Kallmann syndrome (GnRH deficiency with anosmia — KAL1, FGFR1 mutations), functional (obesity, chronic illness, eating disorders, excessive exercise — hypothalamic amenorrhea), medications (opioids, glucocorticoids, GnRH analogs). Clinical manifestations depend on timing: pre-pubertal onset prevents secondary sexual characteristic development (eunuchoid proportions, high-pitched voice, absent puberty); post-pubertal onset causes sexual dysfunction, infertility, muscle loss, osteoporosis, mood changes, and metabolic effects.