The Link Between Amenorrhoea And Stress

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Overview

Menstruation, commonly known as period, occurs in monthly cycles to shed the uterine lining. This natural process is regulated by a complex interplay of hormones. However, disruptions to the normal functions of the menstrual cycle can occur for various reasons, resulting in amenorrhoea—the absence of menstruation.1

One significant factor contributing to amenorrhoea is stress, which manifests as a feeling of pressure or threat. Athletes, people with eating disorders, and those with underlying health conditions are particularly susceptible to this disruption due to the stress imposed by their lifestyle.2 Understanding the intricacies workings of menstruation and recognising risk factors for amenorrhoea is important for promoting reproductive health and identifying potential underlying health issues in people assigned female at birth (AFAB). 

This article will explore how the body responds to stress and how this can, in some instances, lead to temporary or prolonged amenorrhoea, wherein periods cease to occur.

Amenorrhoea

Types of amenorrhoea

There are two main types of amenorrhoea based on when it occurs:

  • Primary amenorrhoea

The absence of a first period by the age of 15, especially when there is breast development; or the absence of a first period within three years of breast development.1 Primary amenorrhoea is often attributed to genetic disorders such as Turner Syndrome or abnormalities of the uterus, such as Müllerian agenesis.3,4

  • Secondary amenorrhoea

The absence of a period for at least three months in a row in people who previously had a regular menstrual cycle.1

Common causes and risk factors

Secondary amenorrhoea has multiple causes and risk factors including:3,5

  • Stress (psychological)
  • Excessive exercise
  • Extreme weight loss or low body weight
  • Not eating enough food
  • Pregnancy or breastfeeding

Conditions that cause secondary amenorrhoea

The following conditions are associated with secondary amenorrhoea:4

Stress and Its effects on the body

Your body can exhibit both a psychological (mind) and physiological (body) response to stress, which leads to physical symptoms. A stress response is triggered when your body perceives a threat.6 You probably think of stress as feelings of anxiety or pressure arising from specific situations which stem from your thoughts. However, stress can also have a broader meaning when it disrupts the normal functions of your body, impacting overall health, as seen in cases of amenorrhoea.

Physiological response to stress

When you are stressed, your body responds to stress signals by releasing hormones from different parts of the brain, and the adrenal gland. This is like when your body gets ready to either fight or flee from danger.

At first, your adrenal gland releases norepinephrine and epinephrine, also known as noradrenaline and adrenaline, into your bloodstream. These hormones increase your heart rate, raise your blood pressure, and speed up your breathing. This process shifts blood flow from non-essential processes, such as digestion, to vital organs and muscles to help you cope with the stress.6

After some time, your brain's hypothalamus releases a hormone called corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH).7 ACTH then triggers the adrenal gland to release more stress hormones, like cortisol and adrenaline.6 

The relationship between stress and amenorrhoea

Impact of stress on hormones and reproductive system

Individuals AFAB have a complex reproductive system that relies on the balance of hormone levels. These hormones include luteinising hormone (LH), follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH), progesterone, and oestrogen. LH and FSH are released from the pituitary gland in response to GnRH. They regulate the growth of follicles in the ovaries leading up to ovulation and the thickening of the uterine lining.8 During the menstrual cycle, the levels of oestrogen and progesterone fluctuate, playing roles in regulating LH level and thickening of the uterine lining, respectively.9

In response to stress, the levels of these hormones can be altered, potentially causing secondary amenorrhoea. Stress triggers changes in hormone levels by reducing GnRH levels in response to circulating corticotropin-releasing hormone (CRH). This decrease in GnRH leads to lower levels of LH, FSH, and oestrogen. When these crucial reproductive hormones are disrupted, ovulation can cease, resulting in missed periods.10 Under normal circumstances, the balance of hormones is regulated by a process called the hypothalamic-pituitary-ovarian (HPO) axis, which usually controls the normal functions of the reproductive system in people AFAB.11,12 However, when GnRH levels are affected by stress, this axis can be thrown off course, impacting reproductive health.

Mechanisms underlying stress-induced amenorrhoea

The majority of cases of secondary amenorrhoea are linked to changes in the normal functioning of the hypothalamic-pituitary-adrenal (HPA) axis.11 The HPA axis acts as a connection between the hypothalamus, pituitary gland, and the adrenal gland, helping to maintain a hormone balance when the body senses stress. The HPA axis is activated in response to stress, which could be from your emotions or physical strain.11 This results in the release of CRH and arginine vasopressin, prompting the pituitary gland to release ACTH. ACTH, in turn, signals the adrenal gland to release cortisol. Increased levels of cortisol in the bloodstream block further production of ACTH and CRH, effectively shutting down the stress response.12

Functional hypothalamic amenorrhoea

A condition that often leads to secondary amenorrhoea due to stress. Functional hypothalamic amenorrhoea reduces levels of GnRH, which then affects reproductive hormone levels, ultimately causing amenorrhoea.13

Diagnosis of stress-induced amenorrhoea

Several laboratory tests can be conducted to check for altered hormone levels associated with amenorrhoea, including:

  • FSH level: Low or normal level is associated with stress-induced amenorrhoea
  • LH level: Low or normal level is associated with stress-induced amenorrhoea
  • FSH and LH levels: High levels of both FSH and LH indicate primary ovarian insufficiency
  • Prolactin level: High levels are associated with hyperprolactinaemia
  • Thyroid stimulating hormone level: A low level indicates hypothyroidism and a high level indicates hyperthyroidism
  • Total testosterone level: A high level is associated with Cushing’s syndrome

Diagnosis should begin with taking a medical history of the patient to assess diet, exercise, any history of eating disorders, weight fluctuations, stresses, and menstrual cycle. Diagnosis should exclude pregnancy and include a measurement of bone mineral density.4

Complications of stress-induced amenorrhoea

There are several complications associated with amenorrhoea due to stress, which need to be addressed to restore reproductive health in people AFAB. 

  • Low bone density

Stress-related amenorrhoea, including functional hypothalamic amenorrhoea, is associated with a decrease in bone density. Hormonal changes, such as high cortisol levels, low GnRH levels, and low levels of IGF-1 and insulin, contribute to bone density lower than normal. Low bone density can also result from an inadequate diet lacking in calcium and vitamin D, as well as excessive exercise and under-eating. Anorexia nervosa, in particular, leads to low bone density due to these factors.13

  • Infertility

As hormone levels in the HPA and HPO axis are altered, the ultimate result is that the body does not release an egg as it normally would during ovulation (a condition known as anovulation). This leads to infertility since fertilisation cannot occur without the release of an egg.10

  • Cardiovascular diseases 

Amenorrhoea leads to lower levels of oestrogen in the body than normal, which has been associated with cardiovascular diseases in people AFAB after menopause. Although this specific relationship hasn’t been studied, it could represent an underlying risk.10

  • Emotional and psychological impact

Amenorrhoea can lead to further emotional stress and anxiety due to concerns about fertility, body image, and worsening symptoms of stress that may have initially induced amenorrhoea. Additionally, underlying conditions that cause amenorrhoea, such as eating disorders, impact mental well-being.

Managing and treating stress-induced amenorrhoea

Recommended treatments aim at restoring health by addressing the stressors contributing to amenorrhoea.

For patients with functional hypothalamic amenorrhoea, restoring the normal functions of the HPO axis is crucial. This can be achieved by increasing calorie intake in those who were under-consuming and improving overall nutrition. In some cases, weight gain may be necessary.

Decreasing exercise activity in athletes experiencing amenorrhoea can help in restoring reproductive health. 

Cognitive behavioural therapy offers support in enhancing emotional well-being and effectively managing overall stress levels for patients.4

Summary

  • Stress is a significant risk factor for amenorrhoea, the absence of period in people AFAB, as it can disrupt the hormonal balance crucial for regular menstrual cycles
  • Secondary amenorrhoea, which occurs in individuals with previously regular periods, is often linked to stress and lifestyle factors such as excessive exercise and extreme weight loss
  • Functional hypothalamic amenorrhoea is a type of amenorrhoea caused by stress. The physiological stress response, involving the hormones in the HPA and HPO axes, disrupts ovulation and the menstrual cycle
  • Diagnosis involves testing hormone levels and a thorough medical history
  • Complications of stress-induced amenorrhoea include low bone density, infertility, potential cardiovascular risks, and emotional impacts
  • Treatments focus on addressing stressors, promoting hormonal balance, and considering lifestyle modifications to restore reproductive health

References

  1. Gibson MES, Fleming N, Zuijdwijk C, Dumont T. Where have the periods gone? The evaluation and management of functional hypothalamic amenorrhea. J Clin Res Pediatr Endocrinol [Internet]. 2020 Jan [cited 2023 Aug 4];12(Suppl 1):18–27. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053439/
  2. Ravi S, Ihalainen JK, Taipale-Mikkonen RS, Kujala UM, Waller B, Mierlahti L, et al. Self-reported restrictive eating, eating disorders, menstrual dysfunction, and injuries in athletes competing at different levels and sports. Nutrients [Internet]. 2021 Sep 19 [cited 2023 Aug 4];13(9):3275. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470308/
  3. Klein DA, Poth MA. Amenorrhea: an approach to diagnosis and management. afp [Internet]. 2013 Jun 1 [cited 2023 Aug 4];87(11):781–8. Available from: https://www.aafp.org/pubs/afp/issues/2013/0601/p781.html
  4. Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, et al. Functional hypothalamic amenorrhea: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism [Internet]. 2017 May 1 [cited 2023 Aug 4];102(5):1413–39. Available from: https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2017-00131
  5. Gordon CM. Functional hypothalamic amenorrhea. N Engl J Med [Internet]. 2010 Jul 22 [cited 2023 Aug 4];363(4):365–71. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMcp0912024
  6. Chu B, Marwaha K, Sanvictores T, Ayers D. Physiology, stress reaction. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 4]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK541120/
  7. Meczekalski B, Niwczyk O, Bala G, Szeliga A. Stress, kisspeptin, and functional hypothalamic amenorrhea. Current Opinion in Pharmacology [Internet]. 2022 Dec 1 [cited 2023 Aug 4];67:102288. Available from: https://www.sciencedirect.com/science/article/pii/S1471489222001151
  8. Tsutsumi R, Webster NJG. Gnrh pulsatility, the pituitary response and reproductive dysfunction. Endocr J [Internet]. 2009 [cited 2023 Aug 4];56(6):729–37. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307809/
  9. Holesh JE, Bass AN, Lord M. Physiology, ovulation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 4]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK441996/
  10. Morrison AE, Fleming S, Levy MJ. A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors. Clin Endocrinol [Internet]. 2021 Aug [cited 2023 Aug 4];95(2):229–38. Available from: https://onlinelibrary.wiley.com/doi/10.1111/cen.14399
  11. Fourman LT, Fazeli PK. Neuroendocrine causes of amenorrhea—an update. J Clin Endocrinol Metab [Internet]. 2015 Mar [cited 2023 Aug 4];100(3):812–24. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333037/
  12. Joseph DN, Whirledge S. Stress and the hpa axis: balancing homeostasis and fertility. Int J Mol Sci [Internet]. 2017 Oct 24 [cited 2023 Aug 4];18(10):2224. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666903/
  13. Meczekalski B, Katulski K, Czyzyk A, Podfigurna-Stopa A, Maciejewska-Jeske M. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest [Internet]. 2014 [cited 2023 Aug 4];37(11):1049–56. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207953/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Lisa Valeria Erika Pugnetti

Master of Science, MSc - Genetics of Human Disease, University College London (UCL)

Bachelor of Science (Hons), BSc - Biology with a Year in Data Analytics, University of Kent


Lisa is a graduate of an MSc in Genetics with a passion for understanding the genetic basis of disease and contributing to high-quality science communication. During her Master’s degree she worked on a project to include individuals of diverse ancestry in genetic studies of major depression, working to reduce healthcare inequalities.

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