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

Abstract

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.

Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

(A) Circulatory concentrations of cortisol in 15 min intervals over 24 h in a woman with FHA before (pre) and after (post) CBT. Meals are indicated by arrows. (B) Circulatory concentrations of cortisol displayed as 8-h mean in the same woman before (pre) and after (post) CBT.

Figure 2

(A) Mean ± SEM levels of nocturnal (2400–0745 h) cortisol levels by treatment arm (observation vs. CBT) and before (pre) and after (post) treatment. CBT reduced cortisol levels (p = 0.006).

Figure 3

Mean ± SEM of (A) BMI, (B) leptin, (C) TSH, and (D) free T3 in women who underwent observation or CBT before (pre) and after (post) treatment. CBT increased leptin levels (B; p = 0.09) and increased TSH levels (C; p = 0.009).