Once a woman (or person with female sex hormones) reaches menopause, things change. I experienced the usual rush of hot flushes, brain fog (later found to be previously undiagnosed ADHD – and responsive to methyphenidate – yay!) and an array of other symptoms like night sweats, sleep problems, wrinkled skin, and lost libido.
Every person who menstruates will, if they live long enough, stop menstruating. The impact of hormone changes over the course of our lives is enormous, and it seems has more of an effect on musculoskeletal pain than we’ve considered. Women are disproportionately represented in chronic pain statistics (Mills, et al., 2019; Zimmer et al., 2022) and female’s nociceptive systems are not the same as males (Osborne & Davis, 2022), so it’s pleasing to see the commitment IASP has made to retaining the ‘DEI’ lens we sorely need.
Some commentators have called for the pain people experience around and after menopause to be called ‘the musculoskeletal syndrome of menopause’ to help clarify what is going on, raise awareness of the issues, and help focus research efforts in this area. The hallmark paper is by Wright et al., (2024) where they argue that by recognising these issues as a specific diagnostic entity there will be increased awareness – similar to the term ‘genitourinary syndrome of menopause’ which has enhanced awareness of and better care for people experiencing genital symptoms such as vaginal dryness, burning and irritation, dysuria and recurrent urinary tract infections.
In the paper by Wright and colleagues (2024), it’s pointed out that musculoskeletal pain in perimenopausal women is about 71% (citing Lu et al., 2020) and higher than in pre-menopausal women. Given that women’s experiences of pain can be dismissed (see Loscar, 2018; Prego-Jiminez, 2022, and Wilford, 2022) and that stereotypes may be applied to women when they seek help (Wratten et al., 2019) it seems important to raise awareness. It’s also important to note that imaging (X-ray, MRI etc) in these people may show no structural changes – the pain seems to be arising from altered processing in the nociceptive system. Note that in saying this, I am not suggesting ‘altered processing’ is at the cortical level – this is not a ‘neurocentric’ take on pain.
What are the mechanisms involved? Well it’s a little difficult to answer because, as we know, pain is a personal experience that is not equivalent to nociception. Some of the theorised mechanisms, according to Wright et al (2024) include:
(1) increased inflammation related to the loss of oestrogen that usually regulates inflammation. 17beta estradiol is thought to be the culprit, as this inhibits TNF-alpha which is an inflammatory cytokine known to reduce how well muscles respond to damage. Oestrogen is also modulated by the ‘inflammasome’ which is part of our immune system and processes pro-inflammatory cytokines, and the inflammasome is also modulated by oestrogen receptor beta. Oestrogen can inhibit pro-inflammatory cytokines that are released with inflammation, and thus regulate the inflammasome, so MHT might be a good option for management.
(2) sarcopenia (loss of muscle mass in older people) involves loss of fast muscle fibres, type ii fibres, reduced motor units and more intra-muscular fat tissue. Sarcopenia leads to greater risk of falls, greater frailty and poorer bone density and the treatment often involves increasing nutrition including proteins, vitamin D and creatine, and resistance training. Interestingly, oestrogen influences energy in cells through changes in mitochondrial function, increased mitochondrial H202 production, reduced antioxidant proteins, and insulin sensitivity because oestrogen is involved in cellular redox and glucose homeostasis in skeletal muscle. Again, MHT may be a useful treatment to counteract the negative effects of lower levels of oestrogen – along with maintaining activity, particularly resistance-based or strength training.
(3) satellite cell proliferation – these cells promote plasticity and regeneration in muscle fibres, and particularly activate after injury or in chronic inflammatory situations. Estradiol stimulates the production of these cells through oestrogen receptors, and when oestrogen is not as present (and therefore not binding to oestrogen receptor alpha, recovery after injury is impaired. While keeping active is a really good thing, recent research suggests that without MHT, fewer satellite cells present may create conditions for more osteopenia and increased frailty because the muscles simply can’t generate enough muscle power or regenerate sufficiently.
(4) bone density has long been seen as a post-menopausal problem, it’s often under-diagnosed and yet it’s both preventable and treatable. Oestrogen deficiency is associated with bone loss, and while treatment can include appropriate nutrition and exercise, it’s probably worth recognising the MHT might have an integral part to play because at least one study shows that it reduced the incidence of osteoporotic bone fractures.
(5) cartilage changes accelerate in menopausal women with some studies demonstrating that oestrogen modulates cartilate and bone remodeling (in rats!) but also in humans when it’s been found to influence intervertebral disc height (Muscat Baron et al., 2007). But, as ever, studies are not equivocal with one study showing greater incidence of knee OA in those taking HRT. Watch this space.
What does all this mean?
For clinicians there are some very clear points to take away.
- Perimenopausal people will likely experience significant changes in their body and pain is often a problem.
- Dismissing a person’s report of pain as ‘because menopause’ and pointing them to counselling or dealing with anxiety is insufficient and inadequate management. Menopause has a myriad of effects including the ones I’ve outlined above – and I haven’t commented yet on the impact of poor sleep on pain! Take reports of pain seriously.
- The absence of findings on imaging to explain reports of pain doesn’t mean the pain is ‘imaginary’! or ‘because menopause’. It does not mean the ’cause’ of a person’s pain is psychological. It simply means imaging is not capturing what is going on – and remember that NO imaging can confirm or disconfirm whether a person is experiencing pain.
- Consider peri-menopause in anyone over the age of 35ish (arbitrary figure, BTW) who has female reproductive organs. Menopause can start earlier than we think. If a person reports pain and any of the other signs and symptoms of menopause, consider menopause as part of the picture.
- MHT can be used even if a person has been in menopause for years. While it’s always a clinical decision, and there’s a need to balance benefits with adverse effects, it seems like MHT on the whole might be a good option for maintaining health of older women. This paper by Shifren, Crandall & Manson (2019) in JAMA might be helpful. This webpage from the Australasian Menopause Society lists research related to menopause and is also an excellent source of information.
Loscar, T. (2108) Not all in her head: how women experience pain differently. EMS World Expo pp 38-41
Lu CB, Liu PF, Zhou YS, et al. (2020) Musculoskeletal pain during the menopausal transition: a systematic review and meta-analysis. Neural Plast. 2020:8842110–8842110. doi: 10.1155/2020/8842110.
Mills SEE, Nicolson KP, Smith BH. Chronic pain: a review of its epidemiology and associated factors in population-based studies. Br J Anaesth. (2019) 123:e273–83. doi: 10.1016/j.bja.2019.03.023
Muscat Baron Y, Brincat MP, Galea R, et al. Low intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures compared to hormone-treated and untreated postmenopausal women and premenopausal women without fractures. Climacteric. 2007;10(4):314–319. doi: 10.1080/13697130701460640.
Osborne NR, Davis KD. Sex and gender differences in pain. Int Rev Neurobiol. (2022):164. doi: 10.1016/bs.irn.2022.06.013
Prego-Jimenez, S., Pereda-Pereda, E., Perez-Tejada, J., Aliri, J., Goni-Balentziaga, O, & Labaka, A. (2022). The Impact of Sexism and Gender Stereotypes on the Legitimization of Lower Back Pain. Pain management nursing.12 p18-25.
Shifren, J. L., Crandall, C. J., & Manson, J. E. (2019). Menopausal Hormone Therapy. JAMA, 321(24), 2458-2459. https://doi.org/10.1001/jama.2019.5346
Wilford, K., Mena-Iturriaga, M., Vugrin, M., Wainer, m., Sizer, P., & Hendrijke, G. (2022). International Perspective on healthcare provider gender bias in musculoskeletal pain management: a scoping review protocol. BMJ Open (12)
Wratten, S., Eccleston, C., & Keogh, E. (2019). Perceptions of gendered and ungendered pain relief norms and stereotypes using Q-methodology. Pain, 160(2), 395-406. https://doi.org/10.1097/j.pain.0000000000001409
Wright, V. J., Schwartzman, J. D., Itinoche, R., & Wittstein, J. (2024). The musculoskeletal syndrome of menopause. Climacteric, 27(5), 466-472. https://doi.org/10.1080/13697137.2024.2380363
Zimmer Z, Fraser K, Grol-Prokopczyk H, Zajacova A. A global study of pain prevalence across 52 countries: examining the role of country-level contextual factors. Pain. (2022) 163:1740–50. doi: 10.1097/j.pain.0000000000002557