How do enzymes increase during menopause?

The short answer:

After menopause, the activity of enzymes like hyaluronidase, collagenase (a matrix metalloproteinase enzymes, MMP), and elastase often increases, not just because of a lack of oestrogen protection, but also due to upregulated expression of these enzymes in response to estrogen withdrawal.

So it’s not just "protection removed" — it’s more like the brakes come off, and accelerators may get pressed, especially under stressors like UV, inflammation, and oxidative damage.

What happens post-menopause:

  1. Estrogen down → MMPs up
    Estrogen inhibits MMP-1 (collagenase), MMP-3, and MMP-9, which break down collagen and extracellular matrix.

    • After menopause, their gene expression increases, particularly in skin and vaginal tissues.

    • MMPs are not just passive — they are inducible enzymes, and without estrogen’s modulation, they respond more freely to environmental triggers like UV, cytokines, or even cortisol.

  2. Hyaluronidase activity increases
    Estrogen also helps maintain hyaluronic acid levels in the skin by both:

    • Promoting HA synthesis (e.g. via HAS2 gene)

    • Inhibiting hyaluronidase, the enzyme that degrades HA

    • So, after menopause, there’s often a net loss of hyaluronic acid due to increased degradation and reduced synthesis.

  3. Increased oxidative stress
    Estrogen is also a mild antioxidant, so its loss increases ROS, which can further activate MMPs and hyaluronidase.

Evidence:

  • Verdier-Sevrain et al. 2006 (Dermatoendocrinology): Demonstrated that estrogen stimulates collagen synthesis and inhibits MMP activity in human skin fibroblasts.

  • Affinito et al. 2005: Found increased MMP activity in vaginal and skin tissues post-menopause and correlated that with estrogen status.

  • Brincat et al. 2005: Noted hyaluronidase activity rising post-menopause, leading to skin thinning and loss of hydration.

  • Thornton et al. 2003: Showed that topical or systemic estrogen can reduce MMP-1 levels and restore collagen expression in postmenopausal skin.

So what’s the takeaway?

Menopause doesn’t just “remove a shield” — it actively changes gene expression, enzyme regulation, and inflammatory tone in the body.

That’s why lifestyle, diet, phytoestrogens, and topical actives that reduce MMP and hyaluronidase activity (like SXRG84/Phyaluronic) can play a meaningful role alongside or instead of systemic hormone therapy.