Infertility, miscarriage, and stillbirth increase early menopause risk

Infertility, miscarriage, and stillbirth increase early menopause risk | Image Credit: © highwaystarz - © highwaystarz - stock.adobe.com.

According to a recent study published in the American Journal of Obstetrics & Gynecology, infertility or miscarriage history increases risks of premature and early menopause.

Menopause begins at an average age of 51 years in White women and 48 to 49 years in Asian women, with menopause before age 40 years defined as premature menopause and menopause at ages 40 to 45 years defined as early menopause. Increased risks of menopause symptoms and noncommunicable diseases are seen in women with premature or early menopause.

Reproductive and health factors have been linked to age at natural menopause, but there is little data on how stillbirth, infertility, and miscarriage impact premature and early menopause. As these reproductive outcomes are associated with shifts in sex hormones, they may impact age at menopause.

Early and premature menopause is more common in Asian women, making it possible there are differences in the associations of reproductive outcomes with age at menopause based on race. Investigators conducted a study to determine the associations of infertility, miscarriage, and stillbirth with age at natural menopause and whether these associations differ by race.

The study, known as the InterLACE, pooled 27 observational studies from 12 countries with over 850,000 women. Of the studies, 9 had data on at least 1 reproductive history and age at menopause. Seven of the studies recruited women at midlife, while the other 2 recruited women at birth. Studies were conducted between 1990 and 2010.

Study entry was defined as baseline in most studies. Participants included women who experienced natural menopause with data on at least 1 reproductive history, possible cofounders, and age at menopause available.

Baseline and follow-up questionnaires were used to gather data on infertility, stillbirth, and miscarriage. Infertility was determined by a lack of successful pregnancy after 12 months of regular, unprotected intercourse. Consolation, diagnosis, or treatment for infertility was also used to determine infertility.

Miscarriages and stillbirths were categorized by the number experienced. Categories included 0, 1, 2, and 3 or more. Recurrent miscarriages were defined as 3 or more, while recurrent stillbirths were defined as 2 or more. 

Surveys were also used to collect data on age at natural menopause, with categories including under 40 years, 40 to 44 years, 45 to 49 years, 50 to 51 years, and 52 or more years. Baseline characteristics collected include education level, smoking status, race and ethnicity, alcohol intake, age at menarche, body mass index, and number of children.

There were 303,594 postmenopausal women included in the analysis, with a median age at natural menopause of 50 years. Premature menopause was seen in 2.1% of women and early menopause in 8.4%. Infertility was experienced by 9.7% of women, miscarriage by 17.5%, and stillbirth by 6.1%. 

Women without data on a reproductive history were excluded from its analysis. This included 13.8% of women for infertility, 3.9% for miscarriage, and 2.8% for stillbirth.

Higher risks of premature menopause and early menopause were seen in women with a history of infertility. Asian women with infertility had a definitive increased risk of premature menopause and possible increased risk of early menopause compared to White women with infertility.

Premature and early menopause risks also increased based on the number of miscarriages a woman experienced. Higher risks were seen in Asian women with miscarriage, especially those with recurrent miscarriages, compared to non-Asian women with an equal number of miscarriages.

A history of stillbirth, especially with recurrent stillbirths, also increased premature and early menopause risks. Asian women were at increased risks of premature and early menopause compared to non-Asian women with an equal number of stillbirths.

These results indicated increased risks of premature and early menopause in women with a history of infertility, miscarriage, or stillbirth, with risks increased further in Asian women Investigators recommended further studies on the causes of infertility or pregnancy loss be conducted.

Reference

Liang C, Chung H, Dobson AJ, et al. Is there a link between infertility, miscarriage, stillbirth, and premature or early menopause? Results from pooled analyses of 9 cohort studies. American Journal of Obstetrics & Gynecology. 2023;229(1).doi:10.1016/j.ajog.2023.04.009