Table 2.
Empirical evidence of the influence of hormone replacement therapy on TL.
| Methods | Study Groups | Studied Molecule | Mechanism and Conclusions | Reference |
|---|---|---|---|---|
| TL by qPCR | G1: 65 women on HT for >5 years G2: 65 women matched in age HT-naive |
Oestrogen and progesterone | G1 exhibited greater TL compared to G2. Long-term HT inhibit TL shortening. |
[170] |
| TL by qFISH | Mice | Oestrogen-replacement therapy (ORT) | ORT resulted in elevated levels of TERT gene expression, enhanced telomerase activity, elongated TL, and stimulated ovarian tissue growth. Oestrogen insufficiency or excessive activity can lead to the ageing of ovarian tissue or the development of tumours, respectively, via influencing the remodelling of telomeres through oestrogen control. |
[171] |
| TL by qPCR | 1048 women in Sister Study | Oestrogen and progesterone | No association between HT and TL. Reproductive histories that indicate higher levels of naturally occurring oestrogen were linked to shorter TL. |
[172] |
| TL by qPCR | 100 newborns from expecting mothers recruited in early pregnancy (tracked prospectively from intrauterine life to early childhood) | Endogenous E3 | An elevation in maternal E3 concentration during the initial stages of pregnancy was linked to a 14.42% rise in child TL. | [173] |
| TRAP for telomerase activity; qPCR for TERT gene expression | G1: female rats G2: female rats with a placebo |
21-day release oestrogen formulation | Without oestrogen, the TERT gene’s expression and telomerase activity were decreased. Oestrogen insufficiency leads to a notable reduction in the TL in the adrenal cortex. Oestrogen for 3 weeks restores TERT gene expression, telomerase activity, and cell proliferation. |
[174] |
| TL by qPCR | G1: 333 breast cancer sister-sets G2: 409 unaffected sisters |
HT | Shortened TL in unaffected sisters showed a statistically significant correlation with HT-naïve sisters. An inverse relationship was detected between the duration of HT and the TL. |
[175] |
| TL by qPCR | G1: 415 females with IPF G2: 718 males with IPF G3: 204,321 healthy females G4: 174,254 healthy males |
Endogenous sex hormones (analysis for the prospective role of HT in telomere maintenance) | Females who experienced early menopause and premature ovarian failure had a greater likelihood of developing IPF. The prevalence of IPF in males was correlated with the levels of bioavailable testosterone in the blood and the stages of the disease. Both males and females showed a correlation between lower levels of sex hormones and shorter TL. Elevated levels of sex hormones provide a protective effect against the development and advancement of IPF, potentially by decelerating the process of TL shortening. Hormonal supplements can potentially delay or prevent the start of diseases in those at risk of telomere-associated IPF and enhance the prognosis of the disease. |
[176] |
| telomerase activity by TRAP; TERT by qPCR | G1: healthy subjects G2: subjects with TERT mutations |
androgens; E2 | Both drugs increased telomerase activity in G1 in a dose-dependent manner, which was associated with higher amounts of TERT mRNA. Sex hormones activate the expression of TERT by binding to the oestrogen receptor, which can then interact with certain regions in the promoter region of the TERT gene. |
[177] |
Legend: TL—telomere length; HT—hormone replacement therapy; qPCR—quantitative polymerase chain reaction; TERT—telomerase reverse transcriptase; TRAP—telomerase repeated amplification protocol; E2—estradiol; E3—estriol; IPF—idiopathic pulmonary fibrosis.