A study including almost half a million people finds that starting periods before the age of 12 increases the risk of heart disease and stroke later in life.

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A range of reproductive factors are linked with health risks in a new study.

As cardiovascular disease (CVD) is the leading cause of death and disability worldwide, it is vital to understand what increases risk.

Although many of the factors involved — such as obesity, hypertension, and smoking — are now well-known, there are still some missing parts to the puzzle.

Certain reproductive factors — which might include early menopause, early periods, or menarche, complications of pregnancy, miscarriage, stillbirth, and hysterectomy — have long been thought to predict CVD later in life.

Some studies, for example, have shown that early menopause might be linked to increased CVD risk, while a history of miscarriage may be linked to an increased risk of coronary heart disease. And, some studies have found a relationship between stillbirth and CVD.

However, other similar investigations failed to find significant links. So, although there is growing evidence that reproductive factors play a role in CVD risk, the exact scope and breadth of the relationship is unclear.

So, researchers from the University of Oxford in the United Kingdom set out to get a more definitive answer. They wanted to know which reproductive factors, if any, increased CVD risk. Their results are published this week in the BMJ.

They delved into data from the U.K. Biobank, which is a population-based study including more than half a million men and women under the age of 69, recruited from 2006 to 2010.

Individuals who enrolled in the study filled out questionnaires covering information on lifestyle, medical history, and their environment. Each participant also had blood, urine, and saliva tests.

In total, 267,440 women and 215,088 men were tracked up to March 2016 or until they had their first stroke or heart attack. None had signs of CVD at the start of the trial.

Of the women, 51 percent came from the most affluent third of the U.K., and 60 percent had never smoked. Their average age was 56 at the start of the study.

Other demographic information included the fact that:

  • their average age at menarche was 13
  • 85 percent had been pregnant
  • 44 percent had two children
  • their average age at first child was 26
  • 25 percent had miscarried
  • 3 percent had had a stillbirth
  • 42 percent of men had fathered two children before the study

Before analysis, a number of potential influencing factors were taken into account. Across 7 years of monitoring, there were 9,054 cases of CVD (5,782 cases of coronary artery disease and 3,489 cases of stroke). Of these cases, 34 percent were in women.

They found that women who had had their first period before the age of 12 had a 10 percent greater risk of CVD compared with those who started at the age of 13 or older.

Also, women who went through the menopause before the age of 47 had a 33 percent increase in CVD risk. The risk was particularly pronounced for stroke, rising to 42 percent.

Similarly, miscarriages were found to increase the risk of heart disease, raising the risk by 6 percent for every miscarriage. Stillbirth increased CVD risk by 22 percent overall, and by 44 percent for stroke.

Women who had undergone a hysterectomy had a 12 percent greater risk of CVD and a 20 percent increase in heart disease risk. If these women had undergone the removal of the ovaries, or an oophorectomy, before the hysterectomy, their risk of CVD was doubled.

Also, women who had children at a younger age saw an increased CVD risk, which dropped by 3 percent with every year older.

The authors advise:

More frequent cardiovascular screening would seem to be sensible among women who are early in their reproductive cycle, or who have a history of adverse reproductive events or a hysterectomy, as this might help to delay or prevent their onset of [cardiovascular disease].”

Some studies had shown that the number of children that a woman has, or parity, increases CVD risk. This relationship was also found in this analysis.

That being said, the same incremental increase in risk was measured in the men — so, rather than being due to biological factors, it is more likely to do with behavioral and psychological factors.

The authors note some limitations. For instance, the study was observational, so it is not possible to draw firm conclusions. The team also relied on participants’ recall of reproductive events, which, in some cases, happened many years prior.

However, because the study involved a large sample size and detailed information on each participant, the findings certainly carry weight.

As ever, more work is needed to illuminate the details behind these interactions. The authors end their paper by saying, “Future studies are needed to confirm the present findings and to clarify the biological, behavioral, and social mechanisms involved.”