GENES AND MENOPAUSE: HOW YOUR DNA SHAPES THE CHANGE

By Dr Lara Varden, PhD, BCHHP, LEHP, CFGP, CFNC | The DNA Company

Menopause is a natural stage in every woman’s life, marking the end of menstrual cycles and fertility While it’s a universal experience, the age at which menopause begins and the symptoms women feel can vary greatly Why do some women breeze through menopause while others struggle with hot flashes, mood swings, or memory lapses? The answer, in part, lies in our genes

We are going to explore how specific genes influence menopause its timing, symptoms, and the transition from perimenopause to postmenopause using the latest scientific research

What Is Menopause and Why Does It Happen?

Menopause usually happens between ages 45 and 55 It’s defined as the point when a woman hasn’t had a period for 12 months The years leading up to this, called perimenopause, can bring hormonal ups and downs, causing symptoms like irregular periods, sleep problems, and mood changes

The main driver of menopause is the gradual decline in ovarian function, leading to lower levels of estrogen and other hormones. But not all women experience menopause the same way. Genetics play an impactful role in determining when menopause starts and how women feel during this transition [1].

Genes That Influence the Timing of Menopause

Studies have found genes influencing the onset of menopause

Some of the most influential are involved in DNA repair, hormone regulation, and the immune system [1,2]

Early menopause can affect fertility and increase the risk of health problems like cognitive decline [3], osteoporosis, and h

1 COMT (Catechol-O-Methyltransferase)

COMT helps break down estrogen and dopamine Some women have a version of the COMT gene (AA) that slows this process This can lead to higher levels of estrogen and dopamine in the brain

Impact: Women with the AA COMT type may have more intense symptoms during menopause, like anxiety, mood swings, or trouble sleeping Their bodies may also struggle to clear estrogen, which can affect hormone balance [5]

2 MAO-A (Monoamine Oxidase A)

MAO-A is an enzyme that breaks down neurotransmitters like serotonin, norepinephrine, and dopamine Research shows that women in perimenopause have higher levels of MAO-A, which can lead to lower levels of these “feel-good” chemicals

Impact: This may explain why depression is more common during perimenopause In one study, perimenopausal women had 34% higher MAO-A levels than younger women, making them more vulnerable to mood disorders [6]

3. DRD2 (Dopamine Receptor D2)

The DRD2 gene affects how the brain responds to dopamine, a neurotransmitter linked to motivation and pleasure. Estrogen boosts DRD2 activity, so as estrogen drops during menopause, dopamine function can decline.

Impact: This may contribute to changes in mood, motivation, and even the risk of depression as women transition into menopause [7]

4 5HTTLPR (Serotonin Transporter)

This gene controls how serotonin is recycled in the brain The short version of 5HTTLPR is linked to a poorer response to antidepressants in menopausal women, possibly because estrogen and serotonin are closely connected s ,

Genes and Hormone Metabolism

Other genes, like CYP19A1, are involved in making estrogen from other hormones Changes in these genes can affect how much estrogen a woman has as she approaches menopause, influencing symptoms like hot flashes, bone loss, and heart health [10]

Genes involved in detoxification, such as GSTT1, GSTM1, and SOD2, help clear harmful byproducts from the body. If these genes aren’t working well, oxidative stress can increase, raising the risk of chronic diseases after menopause [11,12].

What Does This Mean for You?

Understanding your genetic makeup can help predict when menopause might start and what symptoms you might face This knowledge can guide personalized treatments like choosing the right type of hormone therapy, supporting mental health, or targeting specific symptoms

For Practitioners: Genetic testing may help tailor menopause management, from hormone therapy to mental health support

For Women: Knowing your genetic risks can empower you to make lifestyle changes like regular exercise, healthy eating, and stress management to ease the transition

The Future: Personalized Menopause Care p p y ( )

As science uncovers more about the genetic side of menopause, the future of care will become more personalized. By understanding your DNA, you and your healthcare provider can work together to create a menopause plan that’s just right for you.

Published 2012 Jan 22 doi:10 1038/ng 1051

3 Sochocka M, Karska J, Pszczołowska M, et al Cognitive Decline in Early and Premature Menopause Int J Mol Sci 2023;24(7):6566 Published 2023 Mar 31 doi:10 3390/ijms24076566

4 Mishra GD, Davies MC, Hillman S, et al Optimising health after early menopause Lancet 2024;403(10430):958-968 doi:10 1016/S0140-6736(23)02800-3

5 Cleveland Clinic Low Estrogen: Causes, Symptoms, Diagnosis & Treatment. 02/08/2022.

6.Rekkas PV, Wilson AA, Lee VW, et al. Greater monoamine oxidase a binding in perimenopausal age as measured with carbon 11-labeled harmine positron emission tomography. JAMA Psychiatry. 2014;71(8):873-879. doi:10.1001/jamapsychiatry.2014.250

7 Czoty PW, Riddick NV, Gage HD, et al Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys Neuropsychopharmacology 2009;34(3):548-554 doi:10 1038/npp 2008 3

8 Gressier F, Verstuyft C, Hardy P, Becquemont L, Corruble E Menopausal status could modulate the association between 5-HTTLPR and antidepressant efficacy in depressed women: a pilot study Arch Womens Ment Health 2014;17(6):569-573 doi:10 1007/s00737-014-0464-1

9 Konishi K, Cherkerzian S, Aroner S, et al Impact of BDNF and sex on maintaining intact memory function in early midlife Neurobiol Aging 2020;88:137-149 doi:10 1016/j neurobiolaging 2019 12 014

10 Dos Santos BR, Casanova G, da Silva TR, Oppermann K, Spritzer PM Association between the aromatase (CYP19A1) gene variant rs10046 and cardiovascular risk in postmenopausal women Arch Endocrinol Metab 2024;68(Spec Issue):e240087 Published 2024 Nov 6 doi:10 20945/2359-4292-2024-0087

11 Minlikeeva AN, Browne RW, Ochs-Balcom HM, et al SingleNucleotide Polymorphisms and Markers of Oxidative Stress in Healthy Women PLoS One 2016;11(6):e0156450 Published 2016 Jun 7 doi:10 1371/journal pone 0156450

12 de Mendonça E, Salazar Alcalá E, Fernández-Mestre M Role of genes GSTM1, GSTT1, and MnSOD in the development of late-onset Alzheimer disease and their relationship with APOE*4 Neurologia 2016;31(8):535-542 doi:10 1016/j nrl 2014 10 012