Current principles of therapy for functional hypothalamic amenorrhea


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To carry out a systems analysis of the information available in modern literature on the principles of therapy for functional hypothalamic amenorrhea (FHA), including innovative treatment options, the use of leptin and kisspeptin in particular. Material and methods. The review includes the data of foreign and Russian articles found in Pubmed on this topic. Results. The paper gives the data available in the literature on drug and non-drug treatment options. It describes the advantages and disadvantages of existing treatment approaches. Taking into account the key role of stress and eating disorders in the pathogenesis of FHA, the review presents the results of studies of cognitive behavioral therapy, the normalization of eating behavior, and the restoration of positive energy balance. Conclusion. The analysis of the efficiency of FHA therapy modalities shows that to restore regular periods requires that body weight, adipose tissue amount, and leptin level should be normalized, which reflects an energy deficit that occurs in the presence of eating disorders and chronic stress. Management of patients with FHA involves the participation of a gynecologist, a psychotherapist, and a dietitian and the application of approaches aimed at normalizing eating patterns, restoring the mental sphere, and correcting behaviors.

Full Text

Restricted Access

About the authors

Galina E. Chernukha

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: c-galina1@yandex.ru
doctor of medical sciences, professor

Dmitry V. Gusev

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: doctor.dgusev@gmail.com
graduate student

Gyuzyal I. Tabeeva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: doctor.gtab@gmail.com
Candidate of Medical Science, Senior Researcher

Iktoriya Y. Prilutskaya

I.M. Sechenov First Moscow State Medical University

Email: anturiumvika@mail.ru
a 6-year student

References

  1. Berga S.L., Mortola J.F., Girton L., Suh B., Laughlin G., Pham P., Yen S.S. Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J. Clin. Endocrinol. Metab. 1989; 68(2): 301-8.
  2. Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil. Steril. 2006; 86(5, Suppl. 1): S148-55.
  3. Борисенко М.Ю., Петецкая У.С., Уварова Е.В., Агарков В.А., Бронфман С.А., Шерина Т.Ф. Нарушение гендерной идентичности у девочек-подростков с вторичной аменореей. Вестник новых медицинских технологий. Электронный журнал. 2016; 10(4): 281-8.
  4. Genazzani A.D., Ricchieri F., Lanzoni C., Strucchi C., Jasonni V.M. Diagnostic and therapeutic approach to hypothalamic amenorrhea. Ann. N. Y. Acad. Sci. 2006; 1092: 103-13.
  5. Roa J., Tena-Sempere M. KiSS-1 system and reproduction: comparative aspects and roles in the control of female gonadotropic axis in mammals. Gen. Comp. Endocrinol. 2007; 153(1-3): 132-40.
  6. Gordon C.M. Clinical practice. Functional hypothalamic amenorrhea. N. Engl. J. Med. 2010; 363(4): 365-71.
  7. Smith J.T., Acohido B.V., Clifton D.K., Steiner R.A. KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J. Neuroendocrinol. 2006; 18(4): 298-303.
  8. Moschos S., Chan J.L., Mantzoros C.S. Leptin and reproduction: a review. Fertil. Steril. 2002; 77(4): 433-44.
  9. Ahima R.S. Body fat, leptin, and hypothalamic amenorrhea. N. Engl. J. Med. 2004; 351(10): 959-62.
  10. Herpertz S., Albers N., Wagner R., Pelz B., Köpp W., Mann K. et al. Longitudinal changes of circadian leptin, insulin and cortisol plasma levels and their correlation during refeeding in patients with anorexia nervosa. Eur. J. Endocrinol. 2000; 142(4): 373-9.
  11. Andrico S., Gambera A., Specchia C., Pellegrini C., Falsetti L., Sartori E. Leptin in functional hypothalamic amenorrhoea. Hum. Reprod. 2002; 17(8): 2043-8.
  12. Schuiling G.A., Valkhof N., Koiter T.R., Lappohn R.M. Differential effect of est rogen on pituitary responsiveness to GnRH in women with different forms of hypothalamic amenorrhea. Acta Endocrinol. 1990; 122(5): 651-5.
  13. Genazzani A.D., Meczekalski B., Podfigurna-Stopa A., Santagni S., Rattighieri E., Ricchieri F. et al. Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea. Fertil. Steril. 2012; 97(2): 483-8.
  14. Shen Z.Q., Xu J.J., Lin J.F. Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy. J. Endocrinol. Invest. 2013; 36(10): 812-5.
  15. Shaw N.D., Histed S.N., Srouji S.S., Yang J., Lee H., Hall J.E. Estrogen negative feedback on gonadotropin secretion: evidence for a direct pituitary effect in women. J. Clin. Endocrinol. Metab. 2010; 95(4): 1955-61.
  16. Perheentupa A., Ruokonen A., Tapanainen J.S. Transdermal estradiol treatment suppresses serum gonadotropins during lactation without transfer into breast milk. Fertil. Steril. 2004; 82(4): 903-7.
  17. Falsetti L., Gambera A., Barbetti L., Specchia C. Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors. J. Clin. Endocrinol. Metab. 2002; 87(2): 500-5.
  18. Meczekalski B., Podfigurna-Stopa A., Genazzani A. R. Hypoestrogenism in young women and its influence on bone mass density. Gynecol. Endocrol. 2010; 26(9): 652-7.
  19. Fazeli P.K., Klibanski A. Bone metabolism in anorexia nervosa. Curr. Osteoporos. Rep. 2014; 12: 82-9.
  20. Сметник А.А., Сметник В.П., Гависова А.А., Донников А.Е., Иванец Т.Ю., Юренева С.В. Неинструментальный метод скрининга низкой минеральной плотности кости у женщин со вторичной аменореей. Акушерство и гинекология. 2014; 8: 59-64.
  21. Castelo-Branco C., Vicente J.J., Pons F., Martinez de Osaba M.J., Casals E., Vanrell J.A. Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives. J. Reprod. Med. 2001; 46(10): 875-9.
  22. Warren M.P., Miller K.K., Olson W.H., Grinspoon S.K., Friedman A.J. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double- blind, placebo-controlled study. Contraception. 2005; 72(3): 206-11.
  23. Seeman E., Szmukler G.I., Formica C., Tsalamandris C., Mestrovic R. Osteoporosis in anorexia nervosa: the influence of peak bone density, bone loss, oral contraceptive use, and exercise. J. Bone Miner. Res.1992; 7(12): 1467-74.
  24. Strokosch G.R., Friedman A.J., Wu S.C., Kamin M. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-controlled study. J. Adolesc. Health. 2006; 39(6): 819-27.
  25. Warren M.P., Brooks-Gunn J., Fox R.P., Holderness C.C., Hyle E.P., Hamilton W.G., Hamilton L. Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study. Fertil. Steril. 2003; 80(2): 398-404.
  26. Klibanski A., Biller B.M., Schoenfeld D.A., Herzog D.B., Saxe V.C. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J. Clin. Endocrinol. Metab. 1995; 80(3): 898-904.
  27. Gibson J.H., Mitchell A., Reeve J., Harries M.G. Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study. Osteoporos. Int. 1999; 10(4): 284-9.
  28. Gordon C.M., Goodman E., Emans S.J., Grace E., Becker K.A., Rosen C.J. et al. Physiologic regulators of bone turnover in young women with anorexia nervosa. J. Pediatr. 2002; 141(1): 64-70.
  29. Brown J., Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst. Rev. 2016; (12): CD002249.
  30. Borges L.E., Morgante G., Musacchio M.C., Petraglia F., De Leo V. New protocol of clomiphene citrate treatment in women with hypothalamic amenorrhea. Gynecol. Endocrinol. 2007; 23(6): 343-6.
  31. Djurovic M., Pekic S., Petakov M., Damjanovic S., Doknic M., Dieguez C. et al. Gonadotropin response to clomiphene and plasma leptin levels in weight recovered but amenorrhoeic patients with anorexia nervosa. J. Endocrinol. Invest. 2004; 27(6): 523-7.
  32. Welt C.K., Chan J.L., Bullen J., Murphy R., Smith P., DePaoli A.M. et al. Recombinant human leptin in women with hypothalamic amenorrhea. N. Engl. J. Med. 2004; 351(10): 987-97.
  33. Chou S.H., Chamberland J.P., Liu X., Matarese G., Gao C., Stefanakis R. et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc. Natl. Acad. Sci. USA. 2011; 108(16): 6585-90.
  34. Liu G.Y., Liang Q.H., Cui R.R., Liu Y., Wu S.S., Shan P.F. et al. Leptin promotes the osteoblastic differentiation of vascular smooth muscle cells from female mice by increasing RANKL expression. Endocrinology. 2014; 155(2): 558-67.
  35. Jayasena C.N., Nijher G.M., Chaudhri O.B., Murphy K.G., Ranger A., Lim A. et al. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J. Clin. Endocrinol. Metab. 2009; 94(11): 4315-23.
  36. Jayasena C.N., Abbara A., Veldhuis J.D., Comninos A.N., Ratnasabapathy R., De Silva A. et al. Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54. J. Clin. Endocrinol. Metab. 2014; 99(6): E953-61.
  37. Golden N.H., Lanzkowsky L., Schebendach J., Palestro C.J., Jacobson M.S., Shenker I.R. The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa. J. Pediatr. Adolesc. Gynecol. 2002; 15(3): 135-43.
  38. Mallinson R.J., Williams N.I., Olmsted M.P., Scheid J.L., Riddle E.S., De Souza M.J. A case report of recovery of menstrual function following a nutritional intervention in two exercising women with amenorrhea of varying duration. J. Int. Soc. Sports Nutr. 2013; 10: 34.
  39. Lagowska K., Kapczuk K., Friebe Z., Bajerska J. Effects of dietary intervention in young female athletes with menstrual disorders. J. Int. Soc. Sports Nutr. 2014; 11: 21.
  40. Arends J.C., Cheung M.Y., Barrack M.T., Nattiv A. Restoration of menses with nonpharmacologic therapy in college athletes with menstrual disturbances: a 5-year retrospective study. Int. J. Sport Nutr. Exerc. Metab. 2012; 22(2): 98-108.
  41. Fioroni L., Fava M., Genazzani A.D., Facchinetti F., Genazzani A.R. Life events impact in patients with secondary amenorrhea. J. Psychosom. Res. 1994; 38(6): 617-22.
  42. Wilamowska Z.A., Thompson-Hollands J., Fairholme C.P., Ellard K.K., Farchione T.J., Barlow D.H. Conceptual background, development and preliminary data from the unified protocol for transdiagnostic treatment of emotional disorders. Depress. Anxiety. 2010; 27(10): 882-90.
  43. Бронфман С.А., Агарков В.А., Кудаева Л.М., Уварова Е.В., Самохвалова К.В. Ларвированная депрессия и атипичные расстройства пищевого поведения у девочек-подростков с вторичной нормогонадотропной функциональной аменореей. Репродуктивное здоровье детей и подростков. 2012; 5: 77-86.
  44. Berga S.L., Marcus M.D., Loucks T.L., Hlastala S., Ringham R., Krohn M. Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy. Fertil. Steril. 2003; 80(4): 976-81.
  45. Michopoulos V., Mancini F., Loucks T.L., Berga S.L. Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial. Fertil. Steril. 2013; 99(7): 2084-91.
  46. Gordon C.M., Ackerman K.E., Berga S.L., Kaplan J.R., Mastorakos G., Misra M. et al. Functional hypothalamic amenorrhea: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. May 2017; 102(5): 1413-39.
  47. Maher-Loughman G.P. Clinical applications of hypnosis in medicine. Br. J. Hosp. Med. 1980; 23(5): 447-55.
  48. Erickson M.H. Control of physiological functions by hypnosis. Am. J. Clin. Hypn. 1977; 20(1): 8-19.
  49. Tschugguel W., Berga S.L. Treatment of functional hypothalamic amenorrhea with hypnotherapy. Fertil. Steril. 2003; 80(4): 982-5.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies