Menopause’s inflammatory impact and how to reduce it

If you’ve read the earlier articles in our menopause series, you know that many of the issues during and after menopause come from decreased levels of hormones like estrogen and progesterone. Other hormones — like DHEA and pregnenolone — also drop naturally with age. These are often called “precursors” to hormones like estrogen, so low DHEA and pregnenolone can contribute to low estrogen and progesterone as well.

So what do these hormones do to protect the body, and how does losing large amounts of them increase inflammation? Let’s look at the effects on bone, joint, muscle, and brain health — then at how to reduce the inflammation that follows.

Bone, joint, muscle & brain health

Bone health

Bone health needs real attention in the peri-, meno-, and postmenopausal stages. Osteoclasts heal and grow bone by breaking down bone tissue and releasing minerals into the blood — a process called resorption. It’s essential for maintaining blood calcium, but there can be too much of a good thing: unchecked bone breakdown by osteoclasts leads to fragile bones.¹

In an inflamed state, T cells recruit and prolong the life of osteoclasts via interleukin-6 (IL-6). With adequate estrogen, that estrogen inhibits IL-6 and prevents excessive bone breakdown. Low estrogen also sensitizes bone to parathyroid hormone (PTH), further increasing resorption.² The result over time can be lost bone density — osteopenia, or eventually osteoporosis.

The precursors help here too: research finds DHEA may preserve bone mass (and muscle mass) in older women,³ and pregnenolone can help prevent osteoporosis and bone destruction.⁴

Joint health

Estrogen and other hormones also protect joint cartilage. Researchers have found connections between decreased estrogen and arthritis, including osteoarthritis (a degenerative joint disease). In animal studies, estrogen protects joint integrity through complex molecular mechanisms — for example, inhibiting COX-2 mRNA expression in joint cartilage cells. COX-2 produces inflammatory prostaglandins; estrogen blunts those effects and shields cartilage cells from reactive-oxygen-species damage.⁵

Muscle health

Estrogen (and its precursors) affect muscle mass too. Estrogen supports both muscle mass and strength, and postmenopausal women show a rapid decline in muscle mass. While middle-aged men and women respond similarly to nutrition and training, postmenopausal women have a reduced muscle response to nutrition and training compared with men of the same age.⁶ Without these protective hormones, menopausal and postmenopausal women are more open to arthritis, joint pain, stiffness, and muscle aches.

Brain health

Estrogen helps keep neuroinflammation down. In chronic neuroinflammation, microglia are continually activated to produce inflammatory cytokines and clear damaged neurons; if that becomes the brain’s constant state, it opens the door to neurodegenerative diseases like multiple sclerosis, Alzheimer’s, and Parkinson’s. Estrogen has inhibitory effects on neuroinflammation — specifically on microglia — protecting against these diseases and even minor issues like brain fog.⁷

Pregnenolone, a neurosteroid made in the brain, regulates mood and memory and plays neuroprotective, neuroplastic, and neurogenesis roles; low pregnenolone is associated with depression, impaired memory, and hormone fluctuations.⁸ DHEA has similar brain effects, and low levels are associated with cognitive decline such as Alzheimer’s and dementia.⁹ As estrogen’s precursors fall, women lose much of this neuroprotection.

Weight gain & inflammatory fat

As covered in the first article in this series, menopause changes where women gain weight. Before menopause, weight tends to settle on the buttocks and thighs; afterward, hormone shifts move it to the abdomen as visceral fat — which is very inflammatory. Increasing abdominal adiposity raises adipocytokines (cytokines secreted by fat tissue), including C-reactive protein (CRP), IL-6, and tumor necrosis factor-α (TNFα) — all inflammatory. That inflammation can drive conditions like type 2 diabetes, which in turn raises the risk of Alzheimer’s.^10,11

An anti-inflammatory lifestyle & supplements

When women lose the anti-inflammatory effects of hormones during menopause, it’s important to lower inflammation in other ways. Lifestyle comes first — sufficient sleep, lower stress, a nutritious anti-inflammatory diet, and controlling toxin exposure. Alongside those, a few key supplements help keep inflammation down.

Menopausal changes can leave the body more inflamed — but working with a doctor who specializes in functional medicine can make a world of difference. We look for root health issues and customize a plan to your needs, whether you’re years postmenopausal or just entering the transition, in person or via telehealth.