The menopause is associated with a deficiency of reproductive hormones, and accompanied by a significant loss of bone mass. This bone loss is accelerated within the first five years post-menopause. Muscle strength at this time would have important clinical implications for correcting imbalance and preventing falls. The aim of the studies within this thesis were to 1) determine the rate and time course of force loss of the quadriceps muscle group over 12 months in three groups of women with varying hormonal status 2) establish the role of oestrogen in this weakness and 3) investigate the effectiveness of hormone replacement therapy (HRT) in maintaining muscle function.

The reliability of an isokinetic dynamometer and a strain gauge assembly was examined initially to determine the inherent variability of muscle function assessment. Strength of the knee extensors measured on the isokinetic dynamometer was deemed reliable in middle-aged women, although at 1.05 rad/s more practice trials were needed to attain peak torque. Measurements of the knee flexors were highly variable. Maximal voluntary isometric contractions were repeatable using the strain gauge system, for both the knee extensors and first dorsal interosseus (FOI) muscle. There was greater variability in force production generated from electrically stimulated contractions.

Maximal strength of the knee extensors declined by 9.3±4.6 and I0.3±3.1% (mean±SE) for dynamic (1.05 radls) and isometric strength respectively over 9 months in hypoestrogenic post-menopausal women. There were no changes at higher angular velocities, or for handgrip strength. These results support the role of reproductive hormones in influencing force production, which is further endorsed by the observation that females on HRT did not experience a reduction in strength over this time. The force loss was significant only when the post-menopausal and HRT group were compared (p<0.05). The postmenopausal group were within I to 3 years past the menopause, the time period in which bone loss is rapid. This rapid loss of strength would therefore be expected to level out, similarly to bone.

The menopause is an oestrogen-deficient and progesterone-deficient endocrinopathy. It is not possible to identify which hormone, if not both, is responsible for these observed changes in strength. To explore the relationship between acute changes in oestrogen and progesterone and strength, maximal force production of the quadriceps and first dorsal interosseus (FOI) was measured across the menstrual cycle. Maximal strength of the quadriceps was lowest prior to the surge in luteinizing hormone (LH) and reached its peak mid-luteal, a difference of 12.6±4.3% (mean±SE). These changes were significantly different (p<O.OS).From these results, there does not appear to be a role of unopposed oestrogen influencing force production but the pattern of strength changes implicates progesterone. There were no corresponding fluctuations in strength of the FOI, which remained relatively stable across the menstrual cycle. The contractility and fatigue resistance of the quadriceps did not differ significantly between any phase (p>O.OS).The difficulty in isolating oestrogen during the menstrual cycle does not render this a good model to assess its effects upon force production. Maximal strength and fatiguability of the FDI were examined in young women undergoing in vitro fertilisation (IVF) treatment when acute, massive changes in oestrogen are induced. There were no differences in muscle function of the FDI when assessed under very low or high oestrogen changes (p>O.05). The independent effects of oestrogen upon muscle function were not demonstrated here.

Hormone replacement therapy is the most efficacious treatment for preventing menopausally-related bone loss. The results from the longitudinal study suggest that HRT confers protection against muscle weakness as a consequence of ovarian failure. Whether HRT maintains or restores strength was examined in the FDI of post-menopausal women (n=9). The oestrogen only and oestrogen-progestogen phases were compared with baseline measurements. A positive change in strength was observed, although this did not reach significance (p<O.1). The increase in strength (15.2±20.6%) between baseline and the oestrogen-progestogen phase of HRT corroborates the involvement of progesterone in determining muscle function.

The findings suggest that the menopause is associated with a loss of strength, prevented by the administration of HRT. Oestrogen alone does not influence force production, although progesterone is impli~!ed. This has important ramifications in hysterectomised women who are prescribed preparations contammg oestrogen only.