Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial

Fertil Steril. 2013 Jun;99(7):2084-91.e1. doi: 10.1016/j.fertnstert.2013.02.036. Epub 2013 Mar 16.


Objective: To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA.

Design: Randomized controlled trial.

Setting: Clinical research center at an academic medical university.

Patient(s): Seventeen women with FHA were randomized either to CBT or observation.

Intervention(s): CBT versus observation.

Main outcome measure(s): Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.)

Result(s): Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged.

Conclusion(s): In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA.

Clinical trial registration number: NCT01674426.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Academic Medical Centers
  • Amenorrhea / blood
  • Amenorrhea / diagnosis
  • Amenorrhea / physiopathology
  • Amenorrhea / psychology
  • Amenorrhea / therapy*
  • Analysis of Variance
  • Cognitive Behavioral Therapy*
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hypothalamic Diseases / blood
  • Hypothalamic Diseases / diagnosis
  • Hypothalamic Diseases / physiopathology
  • Hypothalamic Diseases / psychology
  • Hypothalamic Diseases / therapy*
  • Leptin / blood
  • Neurosecretory Systems / metabolism*
  • Neurosecretory Systems / physiopathology
  • Pennsylvania
  • Recovery of Function
  • Thyrotropin / blood
  • Thyroxine / blood
  • Time Factors
  • Treatment Outcome
  • Triiodothyronine / blood


  • Leptin
  • Triiodothyronine
  • Thyrotropin
  • Thyroxine
  • Hydrocortisone

Associated data