By: Hemanta Paudel
Editor’s Note: Stress is such a normal part of life that its impact is often taken for granted, but there is more to the story. This week’s summary describes ways the hypothalamic-pituitary-gonadal (HPG) axis interacts with the hypothalamic-pituitary-adrenal (HPA) axis to regulate stress and bring homeostasis, or balance, to the body. Fourth-year medical student Hemanta Paudel summarized a 2017 article [1] by Joseph and Whirledge titled, “Stress and the HPA Axis: Balancing Homeostasis and Fertility.”
Want to learn more about the relationship between stress and fertility? Join us October 10-11, 2025 for the FACTS virtual conference: Lifestyle for Healthy Cycles! Among other health-related topics, FACTS speaker and student elective case study leader, Teresa Kenney, APRN, will share tips to optimize fertility in the face of stress. Register today!
Introduction
Stress is ubiquitous and comes to our lives in many sizes and forms, from physical to emotional and everything in between, and it can have deleterious effects on our bodies. The hypothalamic-pituitary-adrenal (HPA) axis is a primary driver of stress in the human body. This primary response to stress activates some systems and suppresses others. An important example of suppression is the reproductive system. In the reproductive system, the activation of the HPA axis and subsequent release of cortisol impact fertility. [1]
Interplay between HPA and HPG
The hypothalamic-pituitary-gonadal (HPG) axis is the primary driver of fertility and ovulation in women. The activation and release of cortisol through the HPA axis triggered by a stressor mainly inhibits the HPG axis. [1]
The HPG axis consists of the hypothalamus releasing gonadotropin releasing hormone (GnRH), which causes the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). FSH causes the ovaries to form and mature a follicle; under the influence of the LH surge, the ovarian follicle ruptures during ovulation, releasing an egg. It is the release of FSH that causes the ovaries to produce estradiol which, in turn, triggers the LH surge. Progesterone is later released by the corpus luteum to prepare the uterus for implantation and support of the zygote if conception occurs. [1]
The stress-mediated release of high levels of glucocorticoids via the HPA axis inhibits the release of GnRH from the hypothalamus; glucocorticoids also inhibit the pituitary hormones directly as well as end target sex organs, such as the ovaries. [1] This inhibition can result in a change in cycle length and impact other aspects of a woman’s cycle. For example, high levels of stress and suppression of GnRH, FSH, LH, and the ovaries can lead to a cycle where no ovulation occurs (anovulation) or cycle lengths that become abnormally long. [1]
“The stress-mediated release of high levels of glucocorticoids via the HPA axis inhibits the release of GnRH … and suppression of GnRH, FSH, LH, and the ovaries can lead to a cycle where no ovulation occurs (anovulation) or cycle lengths that become abnormally long.”
The emotional stress of not having a child after trying for a while can be debilitating for a couple. [2] The additional stress can result in a feedback loop with further negative impact on fertility and ovulation. By learning to track fertility using modern fertility awareness-based methods (FABMs), a woman can tackle challenges posed by these hormonal shifts.
The Role of Modern FABMs and Fertility Tracking
Modern FABMs can provide valuable information to women, whether tracking cervical mucus with the Billings Ovulation Method or the Creighton Model, or relying on double confirmatory methods, such as sympto-thermal or sympto-hormonal methods. The TwoDay Method provides less information but is easy to use and teach. The Standard Days Method is also available but can be limited, as it is only reliable for women who experience regular cycles between 26 and 32 days long. [3]
Knowledge gained from these methods comes primarily through charting the female cycle, which women can learn from a trained instructor. Tracking fertility with FABMs empowers women and couples through information on when to have intercourse to maximize their likelihood of conception. It can also provide valuable information on medical conditions that affect women and may impact their fertility. Such knowledge gained by collaborating with a trained instructor or physician to learn how to track her cycles can reduce anxiety and stress, and have a positive impact not only on fertility but also on her general wellbeing.
“Tracking fertility with FABMs empowers women and couples through information on when to have intercourse to maximize their likelihood of conception. It can also provide valuable information on medical conditions that … may impact their fertility.”
Reducing Emotional Burden and Stress
Modern approaches to cope with the stress of not being able to conceive are available, and some were developed by patients who faced infertility. Organizations like Organic Conceptions provide emotional support to couples experiencing infertility and can be invaluable to patients needing support. Although not definitive, recent research suggests psychological interventions are valuable and help couples with the psychological burden of infertility and possibly even to increase pregnancy rates. [2] This would be consistent with the mechanisms described above. Excess glucocorticoids in utero have been shown to have deleterious effects even beyond the womb; they are associated with increased anxiety and cognitive issues that may stretch into early adulthood. [1] This would be another reason to ensure stressors are minimized, not only during the time before conception but also throughout pregnancy.
“Although not definitive, recent research suggests psychological interventions are valuable and help couples with the psychological burden of infertility and possibly even to increase pregnancy rates.”
Conclusion
In summary, the activation of the HPA cycle due to stress can have a negative impact on fertility and psychological wellbeing. Modern fertility awareness-based methods and psychological interventions are important tools to mitigate the impact of stress on fertility.
References
[1] Joseph, D. N., & Whirledge, S. (2017). Stress and the HPA axis: balancing homeostasis and fertility. International Journal of Molecular Sciences, 18(10), 2224. https://doi.org/10.3390/ijms18102224
[2] Rooney, K. L., & Domar, A. D. (2018). The relationship between stress and infertility. Dialogues in Clinical Neuroscience, 20(1), 41–47. https://doi.org/10.31887/dcns.2018.20.1/klrooney
[3] Duane M, Stanford JB, Porucznik CA, Vigil P. Fertility Awareness-Based Methods for Women’s Health and Family Planning. Front Med (Lausanne). 2022;9:858977. Published 2022 May 24. doi:10.3389/fmed.2022.858977
ABOUT THE AUTHOR
Hemanta Paudel
Hemanta Paudel is a fourth-year medical student at Kansas City University in Kansas City, Missouri. He completed his undergraduate education at the University of Maryland, Baltimore County. He plans to complete residency in internal medicine and is interested in health education. He enrolled in the FACTS elective to gain a better understanding of natural family planning methods and how to share them with future patients so they feel more empowered over their health and reproductive decisions.
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