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Psychoneuroendocrine Correlates of Secondary Amenorrhea

CITATION:  Nappi, R. E.,  F. Facchinetti, F.  Psychoneuroendocrine correlates of secondary amenorrhea. Arch Womens Ment Health (2003) 6: 83–89

ABSTRACT:  Functional hypothalamic amenorrhea is a common, non-organic and theoretically reversible form of anovulation due to reduced hypothalamic GnRH drive. Numerous studies suggest that this altered hypothalamic homeostasis is caused by a synergism between psychogenic challenge, promoted in part by dysfunctional attitudes, and metabolic compromise induced by undernutrition and overexercise.

The recent growing interest in psychiatric comorbidity underlines the importance of reconsidering the boundaries between psychological disorders and somatic conditions. That not withstanding, it is mandatory in gynecological endocrinology to explore the issue of secondary amenorrhea from a psychoneuroendocrine perspective in order to devise biopsychosocial interventions which address the individual distress. 

In this brief review we will try to critically discuss the issue providing evidences from personal studies as clues for better understanding the extent of the complex psychoneuroendocrine network controlling menstrual function.

References

American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders. 3rd edn. revised, American Psychiatric Association, Washington DC.

American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders. 4. edn. American Psychiatric Association, Washington DC.

Berga SL (1997) Behaviorally induced reproductive compromise in women and men. Semin Reprod Endocrinol 15: 47–53.

Berga SL, Girton LG (1989) The psychoneuroendocrinology of functional hypothalamic amenorrhea. Psychiatr Clin North Am 12: 105–116.

Berga SL, Mortola JF, Yen SSC (1988) Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 66: 242–255.

Berga SL, Mortola JF, Girton L, Suh B, Laughlin G, Pham P, Yen SSC (1989) Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 68: 301–308.

Berga SL, Daniels TL, Giles DE (1997) Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations. Fertil Steril 67: 1024–1030.

Biller BMK, Federoff HJ, Koening JI, Klibanski A (1990) Abnormal cortisol secretion and responses to corticotropinreleasing hormone in women with hypothalamic amenorrhea. J Clin Endocrinol Metab 70: 311–317.

Brown E, Bain J, Lerner P, Shaul D (1983) Psychological, hormonal and weight disturbances in functional amenorrhea. Can J Psychiatry 28: 624–628.

Copeland PM, Sacks NR, Herzog DB (1995) Longitudinal followup of amenorrhea in eating disorders. Psychosom Med 57: 121–126.

Couzinet B, Young J, Brailly S, Le Bouc Y, Chanson P, Schaison G (1999) Functional hypothalamic amenorrhea: a partial and reversible gonadotrophin deficiency of nutritional origin. Clin Endocrinol 50: 229–235.

Devlin MJ, Walsh BT, Katz JL, Roose SP, Linkie DM, Wright L, Vande Wiele R, Glassman AH (1989) Hypothalamic-pituitarygonadal function in anorexia nervosa and bulimia. Psychiatry Res 28: 11–24.

Facchinetti F, Demyttenaere K, Fioroni L, Neri I, Genazzani AR (1992) Psychosomatic disorders related to gynecology. Psychother Psychosom 58: 137–154.

Facchinetti F, Fava M, Fioroni L, Genazzani AD, Genazzani AR (1993) Stressful life events and affective disorders inhibit pulsatile LH secretion in hypothalamic amenorrhea. Psychoneuroendocrinology 18: 397–404.

Fava GA, Trombini G, Grandi S, Bernardi M, Pasquali Evangelisti L, Santarsiero G, Orlandi C (1984) Depression and anxiety associated with secondary amenorrhea. Psychosomatics 25: 905–908.

Fava M, Rosenbaum JF, McCarthy M, Pava JA, Steingard R, Fox R (1992) Correlation between perceived stress and depressive symptoms among depressive outpatients. Stress Med 8: 73–76.

Fioroni L, Facchinetti F, Cerutti GM, Nappi G, Genazzani AR (1991) Personality traits in secondary  menorrhea. J Psychosom Obstet Gynecol 11: 67–76.

Fioroni L, Fava M, Genazzani AD, Facchinetti F, Genazzani AR (1994) Life events impact in patients with secondary amenorrhea. J Psychosom Res 38: 617–622.

Frisch RE, McArthur JW (1974) Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science 185: 949–954.

Gadpaille WJ, Sanborn CF, Wagner W Jr (1987) Athletic amenorrhea, major affective disorders and eating disorders. Am J Psychiatry 144: 939–945.

Gallinelli A, Matteo ML, Volpe A, Facchinetti F (2000) Autonomic and neuroendocrine responses to stress in patients with functional hypothalamic amenorrhea. Fertil Steril 73:812–816.

Garfinkel PE, Lin E, Goering P, Spegg C, Goldbloom D, Kennedy S, Kaplan S, Woodside DB (1996) Should amenorrhea be necessary for the diagnosis of anorexia nervosa? Br J Psychiatry 168: 500–506.

Genazzani AD, Petraglia F, Fabbri G, Monzani A, Montanini V, Genazzani AR (1990) Evidence of luteinizing hormone secretion in hypothalamic amenorrhea associated with weight loss. Fertil Steril 54: 222–226.

Genazzani AD, Petraglia F, Gastaldi M, Volpogni C, Gamba O, Genazzani AR (1995) Naltrexone treatment restores menstrual cycles in patients with weight loss-related amenorrhea. Fertil Steril 64: 951–956.

Genazzani AD, Petraglia F, Gastaldi M, Gamba O, Corazza F, D’ambrigio G, Genazzani AR (1996) Growth hormone (GH)-releasing hormone-induced GH response in hypothalamic amenorrhea: evidence of altered central neuromodulation. Fertil Steril 65: 935–938.

Giles DE, Berga SL (1993) Cognitive and psychiatric correlates of functional hypothalamic amenorrhea: a controlled comparison. Fertil Steril 60: 486–492.

Henderson M, Freeman CPL (1987) A self-rating scale for bulimia: the BITE. Br J Psychiatry 150: 18–24.

Kaye WH, Weltzin TE (1991) Neurochemistry of bulimia nervosa. J Clin Psychiatry 52: 21–28.

Kelley K, Daniels GE, Pol J (1954) Psychological correlations with secondary amenorrhea. Psychosom Med 16: 126–147.

Kiriike N, Nishiwaki S, Nagata T, Maeda Y, Kawakita Y (1988) Gonadotropin response to LHRH in anorexia and bulimia nervosa. Acta Psychiatr Scand 77: 420–426.

Kohmura H, Miyake A, Aono T, Tanizawa O (1986) Recovery of reproductive function in patients with anorexia nervosa: a 10-year follow-up study. Eur J Obstet Gynecol Reprod Biol 22: 293–296.

Kreye RE, Strauss J, Hodcmann CH, Ryan RM (1989) Menstrual cycle abnormalities and subclinical eating disorders: a preliminary report. Psychosom Med 51: 81–86.

Laughlin GA, Dominguez CE, Yen SSC (1998) Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 83: 25–32.

Marcus MD, Loucks TL, Berga SL (2001) Psychological correlates of functional hypothalamic amenorrhea. Fertil Steril 76: 310–316.

Marrazzi MA, Bacon JP, Kinzie J, Luby ED (1995) Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa. Int J Clin Psychopharmacol 10: 163–172.

Menninger K (1939) Somatic correlations with unconscious repudiation of femininity in women. J Nerv Ment Dis 89: 514–517.

Miller KK, Parulekar MS, Schoenfeld E, Anderson E, Hubbard J, Klibanski A, Grinspoon SK (1998) Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional intake. J Clin Endocrinol Metab 83: 2309–2312.

Morgan JF (1999) Eating disorders and gynecology: knowledge and attitudes among clinicians. Acta Obstet Gynecol Scand 78: 233–239.

Mozley PD (1969) Forced femininity: opening pandora’s box. Obstet Gynecol 4: 414–417.

Nappi RE, Rivest S (1995) CRF and stress-related reproductive failure: The brain as a state of the art or the ovary as a novel clue? J Endocrinol Invest 18: 872–880.

Nappi RE, Petraglia F, Genazzani AD, D’Ambrogio G, Zara C, Genazzani AR (1993) Hypothalamic amenorrhea: evidence for the central derangement of hypothalamic-adrenal axis. Fertil Steril 59: 571–576.

Nappi RE, Neri I, Veneroni F, Polatti F, Piccinini F, Facchinetti F (2001) Pituitary LH reserve suggests high risk of bulimia in amenorrheic women. Psychoneuroendocrinology 26: 721–730.

Paykel ES (1987) Methodology of life event research. In: Fava GA, Wise TN (eds), Research paradigms in psychosomatic medicine. Karger, Basel, pp 13.

Perkins RB, Hall JE, Martin KA (1999) Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability and response to neurotransmitter modulation. J Clin Endocrinol Metab 84: 1905–1911.

Peters F, Richter D, Breckwoldt M (1982) Interaction between psychosomatic conflicts and gonadotropin secretion. Acta Obstet Gynecol Scand 61: 439–443.

Petraglia F, D’Ambrogio G, Comitini G, Facchinetti F, Volpe A, Genazzani AR (1985) Impairment of opioid control of luteinizing-hormone secretion in menstrual disorders. Fertil Steril 43: 534–540.

Petraglia F, Vale W, Rivier C (1986) Opioids act centrally to modulate stress-induced decrease in luteinizing hormone in the rat. Endocrinology 119: 2245–2250.

Quigley ME, Sheehan KL, Casper RF, Yen SSC (1980) Evidence for increased dopaminergic and opioid activity in patients with hypothalamic hypogonadotropic amenorrhea. J Clin Endocrinol Metab 50: 949–957.

Rand CSW, Kuldau JM (1992) Epidemiology of bulimia and symptoms in a general population: sex, age, race, and socioeconomic status. Int J Eat Disord 11: 37–44.

Refeinstein EC Jr (1946) Psychogenic or “hypothalamic” amenorrhea. Med Clin North Am 30: 1103–1115.

Reid RL, Van Vugt DA (1987) Weight-related changes in reproductive function. Fertil Steril 48: 905–913.

Reindollar RH, Novak M, Tho SPT, McDonough PG (1986) Adult-onset amenorrhea: a study of 262 patients. Am J Obstet Gynecol 155: 531–533.

Rheingold JD (1964) The fear of being a woman. Grune & Stratton, New York. Rivier C, Rivest S (1991) Effect of stress on the activity of the hypothalamic-pituitary gonadal axis: peripheral and central mechanisms. Biol Reprod 45: 523–532.

Russel G (1972) Premenstrual tension and “psychogenic” amenorrhea: psychophysical interaction. J Psychosom Res 16: 279–287.

Schindler AE, Frik V, Goser R, Keller E (1979) The endocrine profile of psychogenic amenorrhea: correlation of hormonal and psychosomatic findings and effect of therapy. In: Pancheri P, Zichella L (eds), Emotion and reproduction. Academic Press, London, pp 169.

Schweiger U, Pirke KM, Laessle RG, Fichter MM (1992) Gonadotropin secretion in bulimia nervosa. J Clin Endocrinol Metab 74: 1122–1127.

Smith CG, Asch RH (1987) Drug abuse and reproduction. Fertil Steril 48: 355–367.

Speroff L, Glass R, Kase N (1999) Clinical gynecology, endocrinology and infertility. Lippincott Williams & Wilkins, Baltimore.

Spitzer RL (1991) Non purging bulimia nervosa and binge eating disorders. Am J Psychiatry 148: 1097–1098.

Stewart DE (1992) Reproductive functions in eating disorders. Ann Med 24: 287–291.

Stewart DE, Robinson E, Goldbloom DS, Wright C (1990) Infertility and eating disorders. Am J Obstet Gynecol 163:1196–1199.

Verri AP, Nappi RE, Proietti Cecchini A, Vallero E, Luzi S, Zara C (1998) Eating disorders and axis I psychiatric comorbidity in amenorrheic women. Int J Eat Disord 24: 137–146.

Vigersky RA, Andersen AE, Thompson RH, Loriaux DL (1977) Hypothalamic dysfunction in secondary amenorrhea associated with simple weight loss. N Engl J Med 297: 1141–1153.

Warren MP (1996) Eating disorders and the reproductive axis. In: Adashi EY, Rock JA, Rosenwaks Z (eds), Reproductive endocrinology, surgery and technology. Lippincott-Raven, Philadelphia, p 1039.

Yen SSC, Jaffe RB (1991) Reproductive endocrinology, WB Saunders Company, Philadelphia.