Pre-Congress Course

Hypothalamic amenorrhea

Sarah Berga (US)

[Berga] Wake Forest School of Medicine, Winston Salem

Functional hypothalamic amenorrhea (FHA), often termed stress-induced anovulation (SIA), is a type of chronic anovulation that presents clinically as amenorrhea. The proximate cause of anovulation in FHA is insufficient GnRH drive to sustain folliculogenesis. The term “functional” implies reversibility. FHA manifests as a constellation of neuroendocrine alterations including low LH and FSH with FSH>LH, nocturnal hypercortisolemia, and hypothyroxinemia with normal TSH. Behavioral concomitants are highly variable. Dieting and excessive exercise are often initiated to cope with subtle psychosocial challenges. While psychological stress reflects individual valences, metabolic stressors such as undernutrition and exercise are more readily identified. We found that combining multiple metabolic and psychogenic stressors synergistically suppressed ovarian function in monkeys. We also demonstrated that cognitive behavior therapy (CBT) restored ovulation and menstrual cycles in FHA and reversed the classical neuroendocrine concomitants. Specifically, CBT reduced hypercortisolism which led to recovery of ovarian and thyroidal function and increased leptin levels absent weight gain. In contrast to organic HA, functional HA reflects a reversible (often termed allostatic) adaptation to individual circumstance that can be reversed by behavioral changes that improve energy deficits and coping responses to relevant psychological stressors. -Sanders KM, Kawwas JF, Loucks T, Berga SL. Heightened cortisol response to exercise challenge in FHA. AJOG 2017 -Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, Murad MH, Santoro NF, Warren MP. FHA: An Endocrine Society Clinical Practice Guideline. JCEM 2017;102:1413. -Michopoulos V, Mancini F, Loucks TL, Berga SL. Neuroendocrine recovery initiated by cognitive behavioral therapy in FHA: a randomized, controlled trial. FNS 2013;99:2084. -Williams NI, Berga SL, Cameron JL. Synergism betw psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys. AJPEM 2007;29 3:E270. -Brundu B, Loucks TL, Adler LJ, Cameron JL, Berga SL. Increased cortisol in CSF of FHA. JCEM 2006;91:1561. -Berga SL, Marcus MD, Loucks TL, Hlastala S, Ringham R, Krohn MA. Recovery of ovarian activity in FHA treated with cognitive behavior therapy. FNS 2003;80:976. -Berga SL, Mortola JF, Girton L, Suh B, Laughlin G, Pham P, Yen SS. Neuroendocrine aberrations in FHA. JCEM 1989;68:301.