How do hormones work for pain?

By Kate Ferguson, Chief of Staff at Samphire Neuroscience

Hormones often get the blame for menstrual pain - and often not without reason. They can drive cramps, inflammation, and mood changes that make discomfort harder to cope with. But they can also be part of the solution. For many, hormonal treatments bring dramatic relief; for others, they only take the edge off, or come with trade-offs like new side effects.

When it comes to pain, hormones can be both the trigger and the treatment - influencing not just where your pain begins, but how your brain receives, processes, and responds to it.

Hormones don’t “make” pain - they change how you feel it

Pain begins when sensory nerves send danger signals to the brain. Hormones influence that process in two main ways:

• At the source: by affecting inflammation and the sensitivity of the tissues involved (like the uterus during menstruation or pelvic lesions in endometriosis).
• In the brain: by changing how pain signals are processed, amplified, or dampened in key regions such as the prefrontal cortex and motor cortex

In the follicular phase - the time after menstruation (your period) and before ovulation - rising estrogen levels can boost brain chemicals like serotonin and brain-derived neurotrophic factor (BDNF), which help raise your pain threshold, meaning your brain does not categorize most experiences as “painful”. This means many people experience this part of the cycle as a “low-symptom” window.

For some, however, mid-cycle ovulation brings a spike of discomfort known as mittelschmerz. While the timing is hormonally driven - ovulation happens after a surge in luteinizing and follicle stimulating hormones (LH and FSH) - the pain itself is mechanical and inflammatory. When the ovarian follicle ruptures to release an egg, it can spill fluid (and sometimes a small amount of blood) into the abdominal cavity. This fluid can irritate nearby tissues, triggering sharp or aching pain. Inflammatory responses, or conditions like endometriosis, can make ovulation pain more intense or prolonged.

After ovulation, progesterone levels rise. Progesterone influences the GABA system - which normally calms the nervous system - but in high or fluctuating doses during the luteal phase, it can heighten emotional reactivity and make pain feel more intense.

You can read more about how hormones vary across the menstrual cycle here.

Why does some pain become chronic?

Hormones can also affect whether short-term pain becomes long-term. Conditions like endometriosis and primary dysmenorrhea often start with cycle-linked discomfort. Over time, the central nervous system can become “sensitized,” meaning the brain keeps amplifying pain signals even when the original trigger is gone. This helps to explain why some people experience pain throughout the month, not just during their period. While this feels counter-intuitive, this is an evolutionary response that evolved to help the brain adapt to and anticipate the potential for pain, as opposed to being “surprised” by it.

Why do hormonal treatments sometimes help?

Hormonal contraceptives - such as the pill, hormonal IUDs, or injections - work by flattening or altering natural hormone fluctuations. This can:

• Reduce endometrial growth and inflammation - helpful in endometriosis.
• Prevent ovulation - which may lower prostaglandin production and menstrual cramps, as well as prevent mittelschmerz.
• Smooth hormonal peaks and troughs - which can stabilize pain perception and reduce symptom flares in chronic conditions such as endometriosis, fibromyalgia and migraines.

For some, this is life-changing. For others, the relief is partial, or side effects - like mood changes or headaches - outweigh the benefits. Hormones can fuel pain, but in the right context, they can also calm it. For most, however, hormone doses and types are not personalized, often leading to years of trial and error before finding something that works.

But… What do hormones and pain have to do with the brain?

Whether you take hormones or not, your brain remains the control center for how pain is experienced. That’s why brain-based approaches - like Nettle™’s gentle, targeted neuromodulation - are gaining traction. By working directly on the neural circuits involved in pain perception and emotional regulation, they can complement or even replace hormonal strategies for those who want non-hormonal relief.

Hormonal vs. brain-based pain interventions

Table showing the key differences between how hormonal and brain-based interventions work for menstrual concerns.

Where does this leave you?

Hormones can be both the cause and the cure when it comes to menstrual pain. They shape the intensity, timing, and emotional weight of pain signals - and in the right form, can also help calm them. Understanding your own hormonal patterns, and how they interact with your nervous system, is the first step toward finding the right mix of solutions. Samphire helps you uncover those patterns over time, making it easier to see when hormonal treatments, brain-based therapies like Nettle™, or a combination of both, work best for you.

References

• Tu, Y., Zhang, B., Cao, J., Wilson, G., Zhang, Z., & Kong, J. (2019). Identifying inter-individual differences in pain threshold using brain connectome: A test-retest reproducible study. NeuroImage, 202, 116049.

• Mouraux, A., & Iannetti, G. D. (2018). The search for pain biomarkers in the human brain. Brain, 141(12), 3290–3307.

• Maulitz, L., Nehls, S., Stickeler, E., Ignatov, A., Kupec, T., Henn, A. T., Chechko, N., & Tchaikovski, S. N. (2024). Psychological characteristics and structural brain changes in women with endometriosis and endometriosis-independent chronic pelvic pain. Human Reproduction, 39(11), 2473–2484.

• Ding, S., Zhu, T., & Zhang, X., et al. (2018). Role of brain-derived neurotrophic factor in endometriosis pain. Reproductive Sciences, 25(7), 1102–1110.

• As-Sanie, S., Kim, J., Schmidt-Wilcke, T., Sundgren, P. C., Clauw, D. J., Napadow, V., & Harris, R. E. (2016). Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. The Journal of Pain, 17(1), 1–13.

• Iannetti, G. D., Zambreanu, L., Wise, R. G., et al. (2005). Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. Proceedings of the National Academy of Sciences, 102(50), 18195–18200. x

• Nijs, J., Meeus, M., Versijpt, J., Moens, M., Bos, I., & Knaepen, K. (2015). Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: A new therapeutic target? Expert Opinion on Therapeutic Targets, 19(4), 565–576.

• Vannuccini, S., Clemenza, S., Rossi, M., et al. (2022). Hormonal treatments for endometriosis: The endocrine background. Reviews in Endocrine and Metabolic Disorders, 23, 333–355.