Changes in sex hormones during menopause increases risk of cardiovascular problems

Changes in sex hormones during menopause lead to increases in bad cholesterol levels, according to a study published in the European Journal of Preventive Cardiology, a publication from the European Society of Cardiology. According to the researchers from the University of Jyväskylä, Finland, this increases the risk of cardiovascular problems in women undergoing menopause.

Most women undergo menopause between the ages of 48 and 52. This leads to a decline in oestrogen levels and an increase in follicle-stimulating hormone (FSH). Researchers already know that menopause predisposes women to heart disease, but this study shows for the first time that this is because there’s a shift in female sex hormones. These shifts were partially blocked with hormone replacement therapy (HRT).

“Menopause is unavoidable, but it is possible that the negative metabolite shift can be diminished by eating healthily and being physically active,” said study author Dr. Eija K. Laakkonen of the University of Jyväskylä, Finland. “In particular, women should pay attention to the quality of fat in their diet and getting sufficient exercise to maintain cardiorespiratory fitness. HRT is an option that women should discuss with healthcare providers at this point in their lives.”

The study involved 218 perimenopausal women not using HRT. The team measured the levels of 180 compounds, including cholesterol, lipoproteins, and lipids, as well as estradiol and FSH at the beginning of the study and then every 3-6 months until early postmenopause. Menopause was assessed using menstrual diaries and blood FSH levels. Early postmenopause was defined as no periods for six months and high levels of FSH on two consecutive measurements. During the study, 35 women started HRT.

“Our study investigated whether the menopausal hormonal change modulates the metabolite profile measured in blood samples taken before and after menopause. Because the menopausal transition, i.e., the time with variable hormone levels and irregular menses, varies tremendously from person to person, the time points for assessment were individualised,” said Dr. Laakkonen.

The results showed that menopause was associated with a significant change in 85 of all metabolites measured, including higher low-density lipoprotein (LDL) cholesterol (“bad” cholesterol), triglycerides, and fatty acids. Crucially, the researchers showed that these changes were caused mainly by changes in sex hormones. In contrast, women on HRT had higher levels of high-density lipoprotein (“good”) cholesterol and lower levels of LDL cholesterol.

“This study links hormonal changes during menopause to metabolic alterations that promote heart disease. Previous studies did not confirm menopausal status with hormone measurements, meaning that they could not differentiate menopausal effects from ageing,” said Dr. Laakkonen.

“Regarding HRT, very strong conclusions cannot be drawn solely based on our observational study since the number of women starting therapy was small and the type of drug was not controlled. Nevertheless, our findings indicate that initiating HRT early into menopause, i.e., during the menopausal transition, offers the greatest cardioprotective effect. Women considering HRT should discuss it with their healthcare professional since there are numerous choices and some potential contraindications such as cancer or stroke history that need to be considered.”


Karppinen JE, Törmäkangas T, Kujala UM, et al (2022) Menopause modulates the circulating metabolome: evidence from a prospective cohort study. Eur J Prev Cardiol. doi:10.1093/eurjpc/zwac060



Changes in sex hormones during menopause increases risk of cardiovascular problems