A Clinician's Guide to Functional Hypothalamic Amenorrhea

Patients and clinicians alike want to know if stress causes infertility. Stress could impair with reproductive function by a variety of mechanisms, including compromise of ovarian function, spermatogenesis, fertilization, endometrial development, implantation, and placentation. Herein we focus on the pathogenesis and treatment of stress-induced anovulation, which is often termed functional hypothalamic amenorrhea (FHA), with the objective of summarizing the actual knowledge as a clinical guide. FHA is a reversible form of anovulation due to slowing of gonadotropin-releasing hormone pulse frequency that results in insufficient pituitary secretion of gonadotropins to support full folliculogenesis. Importantly, FHA heralds a constellation of neuroendocrine alterations with health concomitants. The activity of the hypothalamic-pituitary-adrenal axis is increased in women with FHA and this observation supports the notion that stress is the cause. The extent of reproductive suppression relates to individual endocrinological and physiological sensitivity to stressors, both metabolic and psychogenic, and chronicity.