Hypothalamic Amenorrhea Part 1: Introduction
DISCLAIMER: This blog post isn’t to substitute a diagnosis or treatment for your condition. You will need to speak to your healthcare practitioner about this.
What Is?
Functional hypothalamic amenorrhea (FHA) or hypothalamic amenorrhea (HA) is when the body stops producing enough female sex hormones (oestrogen and progesterone) and menstruation ceases (amenorrhea) for 3 months or longer. A part of the brain, the hypothalamus, is in charge of sending follicular stimulating hormone and luteinising hormone (FSH and LH) via the hypothalamic-pituitary axis where they will send messages to the reproductive organs to create oestrogen and progesterone.
In HA, there is a reduction in gonadotropin-releasing hormone (GnRH) signalling which in turn will reduce FSH & LH (the hormones which trigger ovulation) levels and ovulation will not occur. Without ovulation, a natural, ovulatory period cannot occur.
It is termed “functional hypothalamic amenorrhea” because there is an absence of organic disorders or structural abnormalities. Lifestyle modifications addressing the causative factors/”root causes” can allow ovulation and menstruation to occur again.
HA can commonly occur due to low body weight, excessive exercise, psychological stress and/or restrictive eating/eating disorders. HA can occur at any weight and with or without weight loss. Women who participate in sports that promote leanness (such as ballet, long-distance running and dancing), diet often, have eating disorders, have “type A” personalities, and/or live a stressful life are at a higher risk for primary or secondary amenorrhea. Athletes, in particular, are three times as likely as the non-athletic population to develop HA compared to non-athletes.
How Is Hypothalamic Amenorrhea Diagnosed?
HA requires a diagnosis of exclusion and will involve multiple investigatory steps. There are numerous reasons why amenorrhea may occur, and these include pregnancy, PCOS, certain medications (e.g. birth control, antidepressants/mood stabilisers), nutritional deficiencies, acute stress, weight gain, premature ovarian failure, turner syndrome, genital tract defects & pituitary gland conditions.
Useful questions to diagnose HA include asking about emotional stress, recent weight loss, current or a history of eating disorders/disordered eating and exercise habits. A personal medical history regarding the individual’s female reproductive health will need to be investigated and relevant questions to ask include the start of menarche when the last cycle was and the regularity of cycles before amenorrhea. Often individuals will have normal ovulatory cycles followed by anovulatory cycles/irregular cycles and then amenorrhea.
Physical examination to assist in the diagnosis of HA includes observing for physical signs of weight loss including hirsutism, hypothermia, pale or thin skin, and oedema in the face and legs. A pelvic ultrasound will be useful to identify if there are any abnormalities or an absence of the uterus or cervix, an obstruction of the outflow tract and to observe the vaginal mucosa.
The hormones that should be tested for include luteinising hormone (LH), follicular stimulating hormone (FSH), estradiol, testosterone, DHEA, cortisol (stress hormone), prolactin, thyroid hormones (TSH, fT3, fT4), lipid profile (total cholesterol, triglycerides, VLDL & LDL), insulin and hepatic function (total protein, albumin, etc). HA is diagnosed when estradiol (E2) is under 50 pg/mL, and FSH and LH is under 10 mIU/ml.
HA is associated with neuroendocrine dysfunction and typically sex hormone-binding globulin (SHBG) levels are reduced. Individuals with HA will often present with increased cortisol (stress hormone), total cholesterol, triglycerides, VLDL & LDL.
In chronic dieters and/or individuals with eating disorders, women will present with hypothyroidism with increased levels of inactive reverse T3, and reduced levels of the thyroid hormones fT3 and fT4. The basal metabolic rate will also often be reduced, and individuals will often struggle to ‘feel warm’/will complain of the cold.
Lastly, it is important to not self-diagnose yourself based on this blog or any other internet/podcast/books/etc. Please see your healthcare practitioner to determine why your period may be absent.
REFERENCES
Baker, F., & Driver, H. (2007). Circadian rhythms, sleep, and the menstrual cycle. Sleep Medicine, 8(6), 613-622. doi: 10.1016/j.sleep.2006.09.011
Bearden, C. (2017). Clinical Nutrition: Functional Hypothalamic Amenorrhea. Today's Dietitian, (19), 12.
Chou, S., & Mantzoros, C. (2018). Bone metabolism in anorexia nervosa and hypothalamic amenorrhea. Metabolism, 80, 91-104. doi: 10.1016/j.metabol.2017.10.009
Current evaluation of amenorrhea. (2008). Fertility And Sterility, 90(5), S219-S225. doi: 10.1016/j.fertnstert.2008.08.038
Dundon, C., Rellini, A., Tonani, S., Santamaria, V., & Nappi, R. (2010). Mood disorders and sexual functioning in women with functional hypothalamic amenorrhea. Fertility And Sterility, 94(6), 2239-2243. doi: 10.1016/j.fertnstert.2010.01.012
Genazzani, A., Chierchia, E., Santagni, S., Rattighieri, E., Farinetti, A., & Lanzoni, C. (2010). Hypothalamic amenorrhea: From diagnosis to therapeutical approach. Annales D'endocrinologie, 71(3), 163-169. doi: 10.1016/j.ando.2010.02.006
Kyriakidis, M., Caetano, L., Anastasiadou, N., Karasu, T., & Lashen, H. (2016). Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice – systematic review. European Journal Of Obstetrics & Gynecology And Reproductive Biology, 198, 131-137. doi: 10.1016/j.ejogrb.2016.01.018
Lania, A., Gianotti, L., Gagliardi, I., Bondanelli, M., Vena, W., & Ambrosio, M. (2019). Functional hypothalamic and drug-induced amenorrhea: an overview. Journal Of Endocrinological Investigation, 42(9), 1001-1010. doi: 10.1007/s40618-019-01013-w
Liu, J., & Bill, A. (2008). Stress-Associated or Functional Hypothalamic Amenorrhea in the Adolescent. Annals Of The New York Academy Of Sciences, 1135(1), 179-184. doi: 10.1196/annals.1429.027
Meczekalski, B., Katulski, K., Czyzyk, A., Podfigurna-Stopa, A., & Maciejewska-Jeske, M. (2014). Functional hypothalamic amenorrhea and its influence on women’s health. Journal Of Endocrinological Investigation, 37(11), 1049-1056. doi: 10.1007/s40618-014-0169-3
Mancini, A., Vergani, E., Bruno, C., Barini, A., Silvestrini, A., & Meucci, E. et al. (2019). Relationships Between Thyroid Hormones, Insulin-Like Growth Factor-1 and Antioxidant Levels in Hypothalamic Amenorrhea and Impact on Bone Metabolism. Hormone And Metabolic Research, 51(5), 302-308. doi: 10.1055/a-0859-4285
O'Donnell, E., Goodman, J., & Harvey, P. (2011). Cardiovascular Consequences of Ovarian Disruption: A Focus on Functional Hypothalamic Amenorrhea in Physically Active Women. The Journal Of Clinical Endocrinology & Metabolism, 96(12), 3638-3648. doi: 10.1210/jc.2011-1223
Klein, D., & Poth, M. (2020). Amenorrhea: An Approach to Diagnosis and Management. American Family Physician, 87(11), 781-788.
Kyriakidis, M., Caetano, L., Anastasiadou, N., Karasu, T., & Lashen, H. (2016). Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice – systematic review. European Journal Of Obstetrics & Gynecology And Reproductive Biology, 198, 131-137. doi: 10.1016/j.ejogrb.2016.01.018
Jamieson, M. (2001). Hormone Replacement in the Adolescent with Anorexia and Hypothalamic Amenorrhea—Yes or No?. Journal Of Pediatric And Adolescent Gynecology, 14(1), 39. doi: 10.1016/s1083-3188(00)00082-6
Seaborg, E. (2017). Functional Hypothalamic Amenorrhea Treatment Guidelines. Retrieved 28 September 2020, from https://endocrinenews.endocrine.org/no-easy-answers-new-hypothalamic-amenorrhea-treatment-guidelines/
Sowińska-Przepiera, E., Andrysiak-Mamos, E., Jarząbek-Bielecka, G., Walkowiak, A., Osowicz-Korolonek, L., & Syrenicz, M. et al. (2015). Functional hypothalamic amenorrhoea — diagnostic challenges, monitoring, and treatment. Endokrynologia Polska, 66(3), 252-268. doi: 10.5603/ep.2015.0033
Torbati, T., Dutra, E., & Shufelt, C. (2017). Hypothalamic Amenorrhea and the Long-Term Health Consequences. Seminars In Reproductive Medicine, 35(03), 256-262. doi: 10.1055/s-0037-1603581
Tranoulis, A., Laios, A., Pampanos, A., Yannoukakos, D., Loutradis, D., & Michala, L. (2018). Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis. Fertility And Sterility, 109(4), 708-719. doi: 10.1016/j.fertnstert.2017.12.028
Wallach, E., & Jewelewicz, R. (1976). The Diagnosis and Treatment of Amenorrheas. Fertility And Sterility, 27(12), 1347-1358. doi: 10.1016/s0015-0282(16)42248-x
