Women with premenstrual disorders (PMDs) have been associated with a higher risk of death from non-natural causes, a study in Sweden has suggested, with under-25s being most at risk.
This supports the importance of careful follow-up for young patients and highlights the need to develop suicide prevention strategies for all women with PMDs, the researchers said.
While they found that women with PMDs did not have a heightened risk of overall mortality (adjusted HR 0.91, 95% CI 0.82-1.02) over a mean follow-up of about six years, they had, however, a greater risk of death due to non-natural causes (HR 1.59, 95% CI 1.25-2.04) and nearly twice the risk of death by suicide (HR 1.92, 95% CI 1.43-2.60) versus women without PMDs, reported Marion Opatowski, PhD, of the Karolinska Institutet in Stockholm, and colleagues in JAMA Network Open.
Women diagnosed with PMDs before 25 more than doubled the risk of all-cause mortality (HR 2.51, 95% CI 1.42-4.42) and death from both suicide (HR 3.84, 95% CI 1.18-12.45) and natural causes (HR 2.59, 95% CI 1.21-5.54) compared with unaffected women, and those with with PMDs diagnosed at ages 45-51 had a lower mortality risk (HR 0.79, 95% CI 0.64-0.97) versus their counterparts without PMDs.
“Because diagnosis is usually delayed, women diagnosed early may have a very severe form of PMDs,” Opatowski told Medpage Today.
“Although suicidal behaviour is more common in young women, the association between PMDs and premature mortality is not completely explained by suicide, which accounts for one-third of the deaths.
“More research is needed to better understand the findings and examine the cause-specific mortality – if they experience more severe disease course, or do not respond well to treatment options, for example.”
PMD symptoms include depression, mood swings, and mood disorders. PMDs encompass both premenstrual syndrome and premenstrual dysphoric disorder, which is a severe form of PMD experienced by 2% to 6% of women of reproductive age.
The latter is classified as a depressive disorder, Opatowski noted.
“Previous studies have linked PMDs with suicidal ideation and behaviours, but this is the first to further demonstrate that they are also at risk for completed suicide, which was not surprising.”
In their analysis, the team used used inpatient, outpatient, and drug dispensing data from Swedish national health and population registries.
Dates of death and underlying causes were tracked through the national death register. Suicides and accidents were considered deaths from non-natural causes.
The study included 406 488 women; of these, 67 748 had clinically diagnosed PMDs from 2002 through 2018. The mean age at PMD diagnosis was about 36.
More than half of the women in the matched cohort lived in the middle of Sweden. About 10% of women with PMDs and 9% of women without PMDs had one or more somatic comorbidity. Psychiatric disorders were more common for women with PMDs (23.8% vs 14.1%).
During a mean follow-up of 6.2 years, 367 deaths occurred among women with PMDs (8.4 deaths per 10 000 person-years), and 1 958 deaths occurred among women without PMDs (9.1 deaths per 10 000 person-years).
The top five top causes of death among the 367 women with PMDs were neoplasms (40.9%), suicide (27.2%), cardiovascular diseases (7.9%), accidents (7.9%), and nervous system diseases (4.9%).
Overall, the findings highlight the importance of a standard care pathway for PMDs and overall awareness of the disorder, the researchers noted.
A multidisciplinary care team including mental health specialists, gynaecologists, general practitioners, and other health professionals may help mitigate negative consequences including suicidal behaviour and premature death, they added.
Study limitations included the fact that PMD was identified through diagnoses received by specialists or through medication receipt, which may exclude many women with PMDs, Opatowski said.
“In addition, the duration of our follow-up restricted our investigation to premature death alone, leaving longer-term outcomes unexplored. Extending the follow-up period would offer valuable insights.”
Study details
Mortality risk among women with premenstrual disorders in Sweden
Marion Opatowski, Unnur Anna Valdimarsdóttir, Anna Sara Oberg et al
Published in JAMA Network Open on 28 May 2024
Importance
Premenstrual disorders (PMDs) adversely affect the quality of life of millions of women worldwide, yet research on the long-term consequences of PMDs is limited, and the risk of mortality has not been explored.
Objective
To estimate the associations of PMDs with overall and cause-specific mortality.
Design, Setting, and Participants
This nationwide, population-based, matched cohort study used data from population and health registers in Sweden. Participants included women of reproductive age with a first diagnosis of PMDs between January 1, 2001, and December 31, 2018. Data analysis was performed from September 2022 to April 2023.
Exposures
PMDs were identified through inpatient and outpatient diagnoses and drug dispensing.
Main Outcomes and Measures
Dates of death and underlying causes were ascertained from the National Cause of Death Register. Conditional Cox regression was used to estimate the hazard ratios (HRs) of overall and cause-specific death (eg, death due to natural or non-natural cause, suicide, or cardiovascular events), adjusting for age, socioeconomic status, and somatic and psychiatric comorbidities; in a separate sibling comparison, models were also adjusted for all factors that sisters share.
Results
A total of 67 748 women with clinically diagnosed PMDs and 338 740 matched unaffected women were included, for a total of 406 488 women. Women with PMDs received a diagnosis at a mean (SD) age of 35.8 (8.2) years. During a mean (SD) follow-up of 6.2 (4.6) years (range, 1-18 years), 367 deaths were observed among women with PMDs (rate, 8.4 deaths per 10 000 person-years; 95% CI, 7.6-9.3 deaths per 10 000 person-years), and 1958 deaths were observed among women without PMDs (rate, 9.1 deaths per 10 000 person-years; 95% CI, 8.7-9.6 deaths per 10 000 person-years). Compared with unaffected women, women with PMDs had increased risk of death due to non-natural causes (HR, 1.59; 95% CI, 1.25-2.04), particularly suicide (HR, 1.92; 95% CI, 1.43-2.60), but they did not have increased risk of overall mortality (adjusted HR, 0.91; 95% CI, 0.82-1.02). Notably, women who received a diagnosis before the age of 25 years experienced higher all-cause mortality (HR, 2.51; 95% CI, 1.42-4.42) and death from both suicide (HR, 3.84; 95% CI, 1.18-12.45) and natural causes (HR, 2.59; 95% CI, 1.21-5.54).
Conclusions and Relevance
The findings of this matched cohort study suggest that women with PMDs are not at increased risk of early death overall. However, the risk was elevated among young women and for death by suicide. This supports the importance of careful follow-up for young patients and highlights the need to develop suicide prevention strategies for all women with PMDs.
Medpage Today article – Suicide risk higher for women with premenstrual disorders (Open access)
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