FHA: Characterization of Metabolic Status, Brain Circuitry, and Stress-Reactivity

Functional Hypothalamic Amenorrhea (FHA), the spontaneous cessation of the menstrual cycle for at least 6 months after menstrual cyclicity has been established, is a common and reversible form of anovulation not due to discernible organic causes. Whereas animal studies suggest an interaction of metabolic and psychosocial stress in the genesis of FHA, the distinct central mechanisms in humans are not clear. On a behavioral level, FHA appears to depend on a complex interplay between individual stress susceptibility, stressful life events, and enduring metabolic challenge due to inappropriate attitudes towards eating and body image. We will use a comparison group of ovulatory, eumenorrheic women (EW) and a contrast group of lean women with polycystic ovary syndrome (PCOS). Although women with FHA and PCOS present with anovulation, each condition differs markedly in pathobiology (and health burden). Contrasting women with FHA to those with PCOS will afford an opportunity to understand more about the interaction between metabolism, stress, and reproduction and to determine the extent to which differences between FHA and EW are attributable to reproductive compromise (anovulation) per se versus specific to the pathogenesis of FHA or PCOS. We have used this approach to great advantage in the past to show that hypercortisolemia was confined to FHA and not PCOS (Berga 1997) and that dysfunctional (unrealistic) attitudes and decreased coping skills were reported more often in FHA than in PCOS and more in PCOS than EW. Further, this approach of comparing 3 groups will allow us to improve therapeutic approaches for two principle causes of anovulatory infertility in women. To accomplish this, we will study women with FHA, PCOS, and normal ovulatory women. The study will take place over 2 months and women will make 4-5 outpatient visits to the Clinical Integration Network Center and will have one overnight stay for frequent blood sampling.

Sex

Female

Minimum age

18 Years

Maximum age

35 Years

Inclusion Criteria:

* Inclusion criteria for participation are a gynecological age (age since menarche) \> 5 and \< 25 years, and chronological age \> 18 years, within 90-110% of ideal body weight as determined by the 1983 Metropolitan height and weight table for women, and exercise \< 10 h/wk and run \< 10 mi/wk, day-awake/night-asleep schedule.
* Women in the FHA and PCOS groups have to fulfill the diagnostic criteria of FHA or PCOS and to have all other causes of amenorrhea and anovulation excluded.

Exclusion Criteria:

* Exclusion criteria are smoking, medications, including psychotropic or illicit drugs, medical, neurological, or ophthalmologic disease except acuity problems, a weight loss or gain of \> 10 lb within a year preceding or since the onset of amenorrhea, a major Axis I disorder other than depression, parturition in the last 12 months and/or lactating in the last 6 months.

• BACKGROUNDBerga SL, Marcus MD, Loucks TL, Hlastala S, Ringham R, Krohn MA. Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy. Fertil Steril. 2003 Oct;80(4):976-81. doi: 10.1016/s0015-0282(03)01124-5. PMID 14556820
• BACKGROUNDMarcus MD, Loucks TL, Berga SL. Psychological correlates of functional hypothalamic amenorrhea. Fertil Steril. 2001 Aug;76(2):310-6. doi: 10.1016/s0015-0282(01)01921-5. PMID 11476778
• BACKGROUNDBerga SL, Loucks TL. Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Ann N Y Acad Sci. 2006 Dec;1092:114-29. doi: 10.1196/annals.1365.010. PMID 17308138