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Study suggests that inflammation is behind period pain

Thursday 23 June 2016

"Scientists have finally discovered why periods hurt so much, following a ground-breaking study into menstrual pain," The Independent reports.

A new study suggests that the pain is caused by acute inflammation, as measured by the C-reactive protein (CRP). CRP is a protein produced by the liver; its levels rise when there is inflammation present in the body.

In this latest research, scientists wanted to see if raised levels of CRP were associated with the often reported feelings of dull painful cramping many women feel before their period. This symptom is a common occurrence in what is known as premenstrual syndrome (PMS).

PMS is the name given to the pattern of physical, psychological and behavioural symptoms that can occur two weeks before a woman's monthly period.

Overall, the study found that middle-aged women with raised CRP levels had about a 26-41% increase in risk of the various PMS symptoms. However, it is difficult to prove direct cause and effect between these two things and exclude the influence of other factors. The findings may also not apply to girls and younger women with PMS.

The authors hope that these results will pave the way for future research into therapeutic treatments for PMS. While not life-threatening, PMS can cause a considerable negative impact on quality of life.

Taking steps to avoid factors associated with increased inflammation – such as smoking, overweight and obesity – may also help.

Where did the story come from?

The US study was carried out by researchers from the University of California, Davis, and was funded by grants from the National Institutes of Health (NIH), the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH).

The study was published in the peer-reviewed medical publication Journal of Women's Health. It is available on an open-access basis and can be read for free online.

The Independent was slightly pre-emptive when reporting that, "a ground-breaking study has found a link between inflammation and PMS". This alleged link cannot be confirmed from the methodology used in this research, which was a cross-sectional analysis. However, the main body of the article was accurate.

What kind of research was this?

This was a cross-sectional analysis of data taken from a long-running cohort study being carried out in the US. It aimed to investigate whether CRP levels (C-Reactive Protein – a blood inflammatory marker) were associated with premenstrual symptoms.

Around 80% of women suffer from PMS and 50% seek medical advice for them, placing a sizeable burden on the healthcare system.

Cross-sectional studies like this are useful in assessing the incidence and prevalence of medical conditions or health indicators, but they are unable to prove causation, and say, for example, that raised inflammatory markers/inflammation cause the symptoms. It's probably more of a complex relationship that could involve other factors. A prospective cohort study would be one of the best ways to validate these findings.

What did the research involve?

The data for this analysis was obtained from the Study of Women's Health Across the Nation (SWAN), which is a longitudinal study of midlife women in the US. SWAN is currently following a cohort of 3,302 women from five ethnic groups at seven clinical institutions across the nation – it continues to collect data on reproductive health, plus demographic and lifestyle factors, through self-reported questionnaires.

As part of the initial questionnaire, participants were asked about their periods and to indicate a yes/no response to eight commonly reported premenstrual symptoms:

  • abdominal cramps/pain
  • breast pain/tenderness
  • weight gain/bloating
  • mood changes/suddenly sad
  • increase in appetite or craving
  • feeling anxious/jittery/nervous
  • back/joint/muscle pain
  • severe headaches

Blood CRP levels were also measured.

This cross-sectional analysis used the data from the baseline visit (in 1996/97) to assess whether CRP levels were associated with pre-menstrual symptoms. Participants were included in the analysis if they were aged 42-52 before or around the time of the menopause, had not undergone a hysterectomy or had both ovaries removed, were not pregnant, and were not using hormone replacement therapy or oral contraceptives at baseline. CRP-levels were categorised into "elevated" (>3mg/L) and "non-elevated" (≤3mg/L) for the analysis.

Other potential risk factors were controlled for to assess the true effect of CRP levels on PMS symptoms. This study included 2,939 women from the original cohort with full data available.

What were the basic results?

Overall, elevated CRP levels (>3mg/L) were significantly related to a 26-41% increased odds of reporting PMS symptoms. However, this relationship varied between different symptoms, suggesting that other mechanisms may be responsible for the occurrence of different symptoms.

The analysis also found that symptoms were reported more by Hispanic women and those around the time of the menopause, and significantly less in Chinese and Japanese individuals, compared to Caucasian or premenopausal women. A higher education (more than high school) and higher annual income were associated with fewer PMS symptoms.

Most symptoms were reported significantly more by obese women, those with active or passive smoke exposure, and women with elevated depressive symptoms.

How did the researchers interpret the results?

The researchers concluded: "These results suggest that inflammation may play a mechanistic role in most PMS symptoms, although further longitudinal study of these relationships is needed. However, recommending to women to avoid behaviours that are associated with inflammation may be helpful for prevention, and anti-inflammatory agents may be useful for treatment of these symptoms."


This study found that middle-aged women with elevated CRP levels were more likely to report symptoms of PMS.

The study had a good sample size, and represented a racially diverse and community-based sample of women who could be generalised to the US population of middle-aged women.

However, there are a few points to bear in mind:

  • It is unclear whether CRP levels were measured two weeks before a woman's period, so the results may differ, depending on the stage of the menstrual cycle.
  • As the researchers acknowledge, some of the associations observed may have resulted from other exposures, such as anti-inflammatory medications, physical activity and depressive symptoms.
  • It is difficult to imply the direction of effect/causation. A longitudinal study would be needed to better assess whether a rise in CRP levels preceded the onset of PMS, or vice versa.
  • No information was collected on the presence of infection in participants, which could have influenced the increased levels of inflammation.
  • Lastly, the findings cannot be applied to girls or younger women. It is also possible that PMS prevalence and associations could differ between women of different cultures and ethnicities than the US population sampled in this study.

The researchers hope that these results will pave the way for future research, as well as potential therapeutic treatments for PMS symptoms through advice about avoidable factors associated with increased inflammation, such as smoking, overweight and obesity.

Usually, a step-wise approach is recommended for PMS. Women with mild symptoms can usually relieve symptoms using over-the-counter painkillers and self-care techniques, such as eating smaller meals more frequently to help reduce bloating.

Women with more severe symptoms should see their GP, as they may benefit from the use of prescription medication.

Read about the treatment options for PMS symptoms.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Period pain: Scientists finally work out why menstruation hurts so much

The Independent, 21 June 2016

Links to the science

Gold EB, Wells C, Rasor MO.

The Association of Inflammation with Premenstrual Symptoms

The Journal of Women’s Health. Published online May 2016