Due to increased longevity, women can expect to live more than one-third of their lives in a post-menopausal state, which is characterised by low circulating levels of oestrogen and progesterone. The aim of this review is to provide insights into current knowledge of the effect of female hormones (or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality and is associated with substantial financial costs. Resistance training and dietary optimisation can counteract or at least decelerate the degenerative ageing process, but lack of oestrogen in post-menopausal women may reduce their sensitivity to these anabolic stimuli and accelerate muscle loss. Tendons and ligaments are also affected by sex hormones, but the effect seems to differ between endogenous and exogenous female hormones. Furthermore, the effect seems to depend on the age, and as a result influence the biomechanical properties of the ligaments and tendons differentially. Based on the present knowledge oestrogen seems to play a significant role with regard to skeletal muscle protein turnover. Therefore, oestrogen/hormonal replacement therapy may counteract the degenerative changes in skeletal muscle. Nevertheless, there is a need for greater insight into the direct and indirect mechanistic effects of female hormones before any evidence-based recommendations regarding type, dose, duration and timing of hormone replacement therapy can be provided.

Although oestrogen replacement therapy (ERT), which can affect the risk of major cancers, has been known to reduce total plasma homocysteine concentrations in postmenopausal women, the mechanisms and subsequent molecular changes have not yet been defined. To investigate the effect of ERT on homocysteine metabolism, thirteen healthy postmenopausal women were enrolled in a double-blind, placebo-controlled, randomized, cross-over study consisting of two 8-week long phases, placebo and conjugated equine oestrogen (CEE; 0·625 mg/d). Concentrations of total plasma homocysteine, vitamin B6 and serum folate and vitamin B12 were measured by conventional methods. Genomic DNA methylation was measured by a new liquid chromatography/MS method and promoter methylation status of the oestrogen receptor (ER)α, ERβ and p16 genes was analysed by methylation-specific PCR after bisulfite treatment. The CEE phase demonstrated a significantly decreased mean of total plasma homocysteine concentrations compared with the placebo phase (8·08 μmol/l (6·82–9·39) v. 9·29 (7·53–11·35), P < 0·05) but there was no difference in the blood concentrations of the three B vitamins. The CEE phase also showed a significantly increased genomic DNA methylation in peripheral mononuclear cells compared with the placebo phase (2·85 (SD 0·12) ng methylcytosine/μg DNA v. 2·40 ± (SD 0·15) P < 0·05). However, there was no difference in promoter methylation in the ERα, ERβ and p16 genes. This study demonstrates that decreased homocysteinaemia by CEE therapy parallels with increased genomic DNA methylation, suggesting a potential new candidate mechanism by which ERT affects the risk of cancers and a possible new candidate biomarker for the oestrogen-related carcinogenesis through folate-related one-carbon metabolism.

Whilst the oral contraceptive pill (OC) has been implicated on a number oif occasions as a cause of sensorineural hearing loss, there are no published reports linking hormone replacement therapy (HRT) to otological symptoms. A case of sensorineural loss with tinnitus following commencement of HRT is described, followed by a discussion outlining the fundamental differences between the OC and HRT, thus expaining why a vascular aetiology is unlikely. It is hypothesized that otological symptoms in such cases may be due to the effect of oestrogens on electrolyte balance disturbing inner ear function and also a direct effect on the auditory pathways mediated in part by alterations in neurotransmitter receptor concentrations.