Early menarche

Patients with later menarche, earlier menopause have higher risk for rheumatoid arthritis

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Key takeaways:

  • A study of UK Biobank data suggests that women with late menarche and early menopause demonstrate a higher risk for RA.
  • Other risk factors were fewer than 33 reproductive years, hysterectomy and oophorectomy.

Menarche after the age of 14 years, or going through menopause before 45 years of age, are among the hormonal and reproductive factors that increase the risk for rheumatoid arthritis, according to data published in RMD Open.

“Female reproductive features, such as puberty, pregnancy, childbirth, menopause, breastfeeding, and exogenous exposure to hormone levels (hormone replacement therapy (HRT) or oral contraceptives) may influence the hormonal environment,” Ling-Qiong Jiang of Anhui Medical University, in China, and colleagues wrote. “For example, Jethwa et al reported reduced RA disease activity in pregnancy and a flare in the postpartum period, while Bengtsson et al reported peak incidence of the disease at menopause.

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Menarche after the age of 14 years, or going through menopause before 45 years of age, are among the hormonal and reproductive factors that increase the risk for RA, according to data. 

“While there is a wealth of literature linking hormonal and reproductive factors to an increased risk of RA, female-specific hormonal and reproductive factors and the gender differences in RA present a burgeoning research path that, to our understanding, has not been entirely explored,” they added.

To explore the link between hormonal and reproductive factors and the risk for RA, Jiang and colleagues analyzed U.K. Biobank data from 223,526 women (mean [SD] age = 56.2 [8.02] years). Among these patients, 1.5% received a first-ever RA diagnosis over a 12.39-year median follow-up.

The researchers used restricted cubic spline to analyze the associations between reproductive factors and RA risk, and Cox proportional hazard regressions to estimate HRs for RA.

According to the researchers, both early — ie, prior to age 12 years — menarche (HR = 1.19; 95% CI, 1.07-1.32) and menarche after the age of 14 years (HR = 1.17; 95% CI, 1.05-1.3) were associated with RA occurrence. However, after adjusting for confounding factors, the effect of early menarche weakened (HR = 1.09; 95% CI, 0.98-1.21), while later menarche still appeared to increase RA risk (HR = 1.13; 95% CI, 1.02-1.26).

As for the effects of menopause, RA risk was greater among postmenopausal patients (HR = 1.19; 95% CI, 1.05-1.36) and those with fewer than 33 reproductive years (HR = 1.39; 95% CI, 1.21-1.59). Women who went through menopause before the age of 45 years demonstrated greater RA risk (HR = 1.46; 95% CI, 1.27-1.67), compared with those who went through menopause at age 50 to 51 years.

RA risk was also heightened among patients reporting a history of hysterectomy (HR = 1.4; 95% CI, 1.25-1.56), oophorectomy (HR = 1.21; 95% CI, 1.08-1.35) and those who had used exogenous hormone replacement therapy (HR = 1.46; 95% CI, 1.35-1.57).

Jiang and colleagues wrote that, contradictory to previous research, pregnancy history had no statistically significant effect on RA risk, including in a sensitivity analysis that factored in overweight and obesity status. However, having four or more children was associated with higher RA risk (HR = 1.18; 95% CI, 1.04-1.34).

“This large prospective study among 223,526 women in the UK Biobank indicates that several hormonal and reproductive factors were associated with the risk of RA,” Jiang and colleagues wrote. “When diagnosing and managing women with RA, hormonal and reproductive aspects should be carefully evaluated.

“In particular, women in later menarche or early menopause require additional attention,” they added. “The findings of this study are significant and form a basis on which novel and target-specific intervention measures to curb the risk of RA in women may be developed. Furthermore, future studies should investigate the involvement of female hormones in the pathophysiology of RA.”

Early Menarche, Menopause Tied to Higher CVD Risk

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Several reproductive factors contributed to a higher risk of cardiovascular disease among women, including early periods and early menopause, researchers found.

A history of hysterectomy was also linked with increased risk of cardiovascular disease (CVD) and coronary heart disease, reported Sanne AE Peters, PhD, and Mark Woodward, PhD, both of the University of Oxford in England.

However, history of oophorectomy, as well as age at first birth, had either no associations or only minor inverse associations with increased risk for cardiovascular disease, the authors wrote in Heart.

They pointed to “increasing evidence” that in addition to traditional risk factors such as elevated blood pressure, smoking, and obesity, certain reproductive factorsmay be linked with later cardiovascular disease, though the evidence is “mixed and inconsistent.”

This cross-sectional analysis of UK Biobank data comprised 267,440 women and 215,088 men ages 40 to 69 without a history of cardiovascular disease. The authors found that during 7 years of follow-up, there were 9,054 cases of cardiovascular disease, 5,782 cases of coronary heart disease, and 3,489 cases of stroke. Women comprised about a third of cardiovascular disease cases, a little under 30% of coronary heart disease cases, and about 40% of stroke cases.

Examining demographic data for women, the mean age was 56, about half were from a higher socioeconomic bracket in the U.K., and 60% said they never smoked.

Results were mixed for certain reproductive factors and increased risk for cardiovascular disease. The mean age for menarche was 13 years, and women who had their first periods prior to age 12 had a higher risk of cardiovascular disease (adjusted HR 1.10, 95% CI 1.01-1.30) than women who had menarche at a later age. Similar increased risks were seen for coronary heart disease (adjusted HR 1.05, 95% CI 0.93-1.18) and stroke (adjusted HR 1.17, 95% CI 1.03-1.32).

 Sixty-one percent of women in the study were postmenopausal, with a mean age at natural menopause of 50 years. But early menopause was also linked with increased risk of cardiovascular disease (adjusted HR 1.33, 95% CI 1.19-1.49), coronary heart disease (adjusted HR 1.29, 95% CI 1.10-1.51), and stroke (adjusted HR 1.42, 95% CI 1.21-1.66).

Likewise, history of hysterectomy was linked with an increased risk of cardiovascular disease (adjusted HR 1.12, 95% CI 1.03-1.22) and coronary heart disease (adjusted HR 1.20, 95% CI 1.07-1.34).

Eighty-five percent of women had been pregnant, and 44% of women had two children, while 42% of men had fathered two children. Compared with women and men without children, there was a significantly higher risk of coronary heart disease in women (adjusted HR 1.21, 95% CI 1.05-1.40). But because these risks were similar among men (adjusted HR 1.13, 95% CI 1.04-1.23), the authors concluded that “this is unlikely to be due to a biological cause.”

The authors suggested that, “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 CVD.”

Early Menarche, Menopause Tied to Higher CVD Risk

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More frequent heart screening for women may be useful

Several reproductive factors contributed to a higher risk of cardiovascular disease among women, including early periods and early menopause, researchers found.

A history of hysterectomy was also linked with increased risk of cardiovascular disease (CVD) and coronary heart disease, reported Sanne AE Peters, PhD, and Mark Woodward, PhD, both of the University of Oxford in England.

However, history of oophorectomy, as well as age at first birth, had either no associations or only minor inverse associations with increased risk for cardiovascular disease, the authors wrote in Heart.

They pointed to “increasing evidence” that in addition to traditional risk factors such as elevated blood pressure, smoking, and obesity, certain reproductive factorsmay be linked with later cardiovascular disease, though the evidence is “mixed and inconsistent.”

This cross-sectional analysis of UK Biobank data comprised 267,440 women and 215,088 men ages 40 to 69 without a history of cardiovascular disease. The authors found that during 7 years of follow-up, there were 9,054 cases of cardiovascular disease, 5,782 cases of coronary heart disease, and 3,489 cases of stroke. Women comprised about a third of cardiovascular disease cases, a little under 30% of coronary heart disease cases, and about 40% of stroke cases.

Examining demographic data for women, the mean age was 56, about half were from a higher socioeconomic bracket in the U.K., and 60% said they never smoked.

Results were mixed for certain reproductive factors and increased risk for cardiovascular disease. The mean age for menarche was 13 years, and women who had their first periods prior to age 12 had a higher risk of cardiovascular disease (adjusted HR 1.10, 95% CI 1.01-1.30) than women who had menarche at a later age. Similar increased risks were seen for coronary heart disease (adjusted HR 1.05, 95% CI 0.93-1.18) and stroke (adjusted HR 1.17, 95% CI 1.03-1.32).

Sixty-one percent of women in the study were postmenopausal, with a mean age at natural menopause of 50 years. But early menopause was also linked with increased risk of cardiovascular disease (adjusted HR 1.33, 95% CI 1.19-1.49), coronary heart disease (adjusted HR 1.29, 95% CI 1.10-1.51), and stroke (adjusted HR 1.42, 95% CI 1.21-1.66).

Likewise, history of hysterectomy was linked with an increased risk of cardiovascular disease (adjusted HR 1.12, 95% CI 1.03-1.22) and coronary heart disease (adjusted HR 1.20, 95% CI 1.07-1.34).

Eighty-five percent of women had been pregnant, and 44% of women had two children, while 42% of men had fathered two children. Compared with women and men without children, there was a significantly higher risk of coronary heart disease in women (adjusted HR 1.21, 95% CI 1.05-1.40). But because these risks were similar among men (adjusted HR 1.13, 95% CI 1.04-1.23), the authors concluded that “this is unlikely to be due to a biological cause.”

The authors suggested that, “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 CVD.”

Early menarche may predict overall obesity.

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Cardiovascular disease is the leading cause of death in women in the United States, but little is known about the effect of reproductive factors. In a recent substudy of the Framingham Heart Study, researchers determined that earlier age of menarche is linked to overall obesity.

“The purpose of this study was to examine whether female reproductive risk factors — including onset of menarche, number of births over a lifetime (parity), onset of menopause and menopausal status — are all associated with indices of body fat composition,” researcher Caroline S. Fox, MD, MPH, of the National Heart, Lung, and Blood Institute, said in a press release.

Researchers analyzed 1,638 patients (aged 40 years or older; weighing less than 160 kg) from the multidetector CT (MDCT) substudy of the Framingham Heart Study (FHS) from 2002 to 2005. The patients were offspring of the FHS and third-generation cohorts.

Besides female reproductive risk factors measured, the researchers also looked at visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) via MDCT.

To better understand the influences of body fat and female reproductive risk factors, the researchers also adjusted for covariates such as age, smoking status, alcohol consumption, physical activity, hormone therapy use and menopausal status.

According to data, earlier age of menarche was associated with increased BMI, waist circumference, VAT and SAT (all P<.0001). The researchers wrote that for each 1-year increase in menarche age, VAT was 61 cm3 lower. However, this association of earlier menarche with adiposity measures was weakened after adjustments for BMI. Associations between adiposity and parity, besides menopausal age, were not statistically significant, they added.

Although postmenopausal women had increased BMI, waist circumference, VAT and SAT compared with premenopausal women, the researchers said this was due to increased ages among postmenopausal women.

“This research suggests that select female reproductive risk factors, specifically onset of menarche, are associated with overall adiposity, but not with specific indices of body fat distribution,” researcher Subbulaxmi Trikudanathan, MD, of Harvard Medical School, said in a press release. “Ultimately, the important question is whether female reproductive risk factors can be used to target lifestyle interventions in high-risk women to prevent the metabolic consequences of obesity and cardiovascular disease.”

The researchers suggest that further studies determine whether female reproductive factors can be used in lifestyle interventions among women at high risk for the metabolic consequences of obesity and CVD.

  • Source: Endocrine Today