Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.
Borrás. C C; Ferrando. M M; Inglés. M M; Gambini. J J; Lopez-Grueso. R R; Edo. R R; Mas-Bargues. C C; Pellicer. A A; Viña. J J
Key Findings
- Medically induced menopause sharply reduces estrogen, progesterone, antioxidant gene expression (MnSOD, GPx, etc.) and blood glutathione levels.
- Estrogen replacement therapy restores estrogen levels and significantly increases expression of antioxidant and longevity‑related genes (MnSOD, GPx, P53, P21, TERF2) and blood glutathione.
- Progesterone addition further raises some antioxidant genes (MnSOD, P53, SENS2, TERF2) compared to baseline.
Practical Outcomes
- For biohackers, the data suggest that controlled estrogen replacement can enhance the body’s antioxidant machinery, which may support longevity and metabolic health. However, any hormone therapy should follow medical dosing guidelines and be supervised, as the study used clinical replacement levels and did not assess long‑term safety.
Summary
The study shows that when women’s natural hormones are temporarily shut down (like with a GnRH drug such as triptorelin), their blood cells lose important antioxidant and longevity‑related gene activity. Giving back estrogen (and later progesterone) restores those genes and raises the body’s main antioxidant, glutathione, suggesting hormone replacement can boost cellular defenses against aging.
Abstract
Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.
Study Information
pubmed
2021
2021-09-09T00:00:00.000Z
10.1155/2021/8101615
27
48