Physical functioning measures are considered markers of aging1 integrating those physiologic, cognitive, environmental, and social factors required to accomplish fundamental tasks such as walking, climbing, lifting, carrying, and seeing.2 Measures of functional limitations are clinically relevant endpoints because of the associated increase in falls and fractures, mobility challenges, decline in quality of life, and contribution to increased healthcare costs.3–8 In women, physical functional limitations are frequent, particularly later in life.
Whether menopause or the menopause transition is associated with an accelerated decline in physical functioning is uncertain. However, it has been projected that by age 45, well within the time frame of the menopause transition, up to 10–15% of women could be classified as disabled.9 There is a dearth of information about the events of the menopause transition and their relation to physical functioning. One of the few studies, a cross-sectional investigation of 14,427 multiethnic women enrolled the Study of Women's Health Across the Nation found that women reporting substantial functional limitations were significantly more likely to be surgically or naturally postmenopausal compared with those with no limitations, after adjustment for age, race, body size, and economic stress.10 These cross-sectional findings of the Study of Women's Health Across the Nation were corroborated by a cross-sectional analyses of 1,497 women living on Kinmen island, just east of mainland China, although this analysis was unadjusted for demographic and health factors.11
This report describes the evidence for physical functioning losses in a population-based sample of women at the midlife studied longitudinally over 5 years. The study, which incorporates both perception of functioning based on an interview as well as performance measures, characterizes whether losses are related to the natural menopause, hysterectomy, or time, after adjustment for body size and smoking behavior.
MATERIALS AND METHODS
The Michigan Bone Health and Metabolism Study is a population-based longitudinal study of musculoskeletal disease and physical functioning in white women.12 The 664-woman sample was identified from two sampling frames, the family records of the now defunct Tecumseh Community Health Study and a 1992 Tecumseh community census. In 1992, 80% of the 24–44-year-old female offspring from Tecumseh Community Health Study were recruited. Also recruited in 1992 were 90% of those female residents who were not in the Tecumseh Community Health Study family records but were listed in a community census (Kohl's Directory). University of Michigan Institutional Review Board approval was granted for the study protocol and informed consent was obtained from each participant.
Data measurements from 2000/01 through 2005/06 were included in the longitudinal analyses for this report; in 2003, there was no annual visit due to lapse in funding. Measurements were selected to characterize perceived and performance-based aspects of physical functioning, including upper body and lower body muscle strength, flexibility and range of motion, balance, and coordination. The perception of physical functioning capacity was derived from an interview measure (Medical Outcomes Study SF-36 10-item physical functioning scale), which has been extensively evaluated for construct validity, internal consistency, and test-retest reliability in diverse ethnic groups and age ranges.13–16 The physical functioning scale includes a three-item response of “limited a lot,” “limited a little,” or “not limited at all” to the following items: vigorous activities; lifting or carrying groceries; climbing several flights of stairs; climbing one flight of stairs; bending, kneeling, or stooping; walking more than one mile; walking several blocks; walking one block; and bathing or dressing. The scale is scored using norm-based methods and transformed to have a mean of 50 (standard deviation ±10) in the general U.S. population. Lower scores suggest a perception of greater limitation.
A portable isometric chair, a replicate of the chair designed for the Dynamics of Health, Aging and Body Composition Study17 was used to measure leg strength. Quadriceps strength is measured as torque or the product of force and the torque arm length. Torque (Nm) from three successful trials was averaged. The left leg was tested unless participants reported knee surgery, knee replacement, or pain, conditions under which the alternate leg was tested.
To assess grip strength, a participant was seated in a chair with her forearm at a 90- degree elbow bend and hands placed with fingers and thumb parallel to her body. Three consecutive grip strength (kg) efforts were completed by each participant. The values for each hand were averaged.
Each participant was timed in two purposeful walks down a 40-foot carpeted (commercial knap) corridor. Measures of gait, including velocity, were obtained from an instrumented mat (Gaitrite, CIR Systems, Clifton, NJ) with an 80-Hz sampling frequency, placed midway in the corridor while women completed the second 40-foot walk. Individual footsteps recorded during the walk were displayed on a computer screen, and incomplete footsteps were manually removed.
Participants were timed during their ascent and descent of three standardized stairs fitted with rubber traction strips. Timing commenced with the toe-off of the leading leg at the start of ascent and ended with the final foot contact of the trailing leg after descent.
In chair-rise sit-to-stand performance, participants rose from a standard height, armless chair with arms folded over their chest. Movement time was measured from onset of trunk motion on the chair to achievement of an upright standing position.
In the forward reach measurement, participants were asked to stand, extend their arm at 90 degrees while standing perpendicular to the floor, and then reach the greatest distance (cm) possible forward while maintaining their arm at the same plane established in the perpendicular stance. For all performance-based measures, between- and within-rater comparisons were made. Intrarater percent coefficient of variation ranged from less than 4% (for velocity) to less than 5% (for leg strength), whereas interrater reliability ranged from less than 4% (for velocity) to less than 7% (for leg strength).
Menopausal status was based on the regularity of menstrual bleeding in the year before the study visit. A woman was classified as premenopausal if she had no menstrual irregularity in the previous year, defined as nine or more cycles in the past 12 months. Perimenopause was defined as having menstrual irregularity. Postmenopause was characterized as having at least 12 consecutive months of amenorrhea associated with no other medical cause. Final menstrual period was defined retrospectively as 12 months of amenorrhea with no alternative explanation.
Hormone therapy and oral contraceptive use, including duration, was assessed at each visit and hereafter will be referred to as HT because estrogen-based oral contraceptive preparations are used for menopause bleeding or symptoms in addition to contraception. Due to change in formulations and type of preparation over time, specific HT types were not addressed in subgroup analyses. Hysterectomy and oophorectomy were verified by medical record abstraction. For these analyses, separate transition stages based on HT use in surgical or natural menopause were defined. Medical records were requested to corroborate abdominal surgeries, and based on these records, 87 (approximately 70%) hysterectomies with and without unilateral or bilateral oophorectomy were confirmed. Unless otherwise noted, analyses included censoring information at time of surgery from participants with hysterectomy and/or no ovarian conservation or HT and participants with hysterectomy and ovarian conservation and/or HT for whom medical records could not be obtained.
Height (cm) and weight (kg) were measured at each study visit with a stadiometer and balance-beam scale, respectively. Body mass index (BMI) was calculated by dividing the weight (in kg) by the square of the height (in meters), and it was treated as a time-varying covariate in all models. Participants who reported current consumption of 7 or more cigarettes per week were classified as current smokers for that examination period. Smoking data were also treated as a time-varying covariate.
Performance and body size measures were evaluated for presence of outliers and marked deviations from the normal distribution using plots and residual analyses. When necessary, transformations were employed to assure more normal data distributions. Analysis of covariance was used to estimate the least squared means of age, BMI, and physical functioning measures, F tests were used to evaluate overall statistical significance, and t tests were used to assess pairwise differences. Use of the Benjamini-Hochberg false discovery rate indicated that findings reported with statistically significant P values were not false positives. Longitudinal mixed modeling was undertaken using SAS 9 (SAS Institute Inc., Cary, NC), and models were adjusted for BMI and current smoking status. Over the 5-year period in which performance measures were assessed, there were 2,017 observations from 544 women, who contributed from one to four data points each.
The mean age (±standard deviation) of the sample was 44.8 (±4.8) years in 2000/01 when annual collection of a more comprehensive battery of physical functioning measures was initiated. Mean (±standard deviation) BMI was 28.6 (±6.3), and approximately 60% (n=327 of 544, before censoring unconfirmed hysterectomy/double oophorectomy) of participants had a final menstrual period by 2005/06. Participant characteristics and physical functioning measures at 2005–2006 are shown by menopausal status in Table 1.
Significant differences existed between menopausal status categories for almost all physical functioning variables (Table 1). Least squared mean velocity was 149 cm/s in women with hysterectomy and ovarian conservation/HT compared with 170 in premenopausal women and 175 in naturally post women with HT and women in the HT use category. The least squared mean SF-36 physical functioning score was 80 (of 100) for women with hysterectomy and 77 in women with hysterectomy and an estrogen source, compared with a score of 91 in premenopausal and perimenopausal women.
Annualized rates of change in the physical functioning measures are shown in Table 2. The mean decline in perception of physical functioning (SF-36) was nearly one half point per year. Performance measures with the greater annual changes relative to their baseline values included greater time to lift a 2-pound weight (+2.9%/year), less leg strength (Nm, –2.6%/year), and greater time for the stair climb and walk (+1.9%/year and +1.4%/year, respectively). Distances became shorter in the forward reach measure.
Two menopause transition groups demonstrated significant 5-year changes in physical functioning, women with hysterectomy and women with natural menopause, after adjustment for time, BMI, and smoking behavior. Compared with premenopausal and perimenopausal women, women with confirmed hysterectomy (both those with and without estrogen availability) took longer to lift 2 lb and required more time for rising in sit-to-stand, walking 40 feet, as well as ascending and descending three stairs over the 5-year period. This is demonstrated in Table 3, which shows the changes in physical functioning performance over time, with regression coefficients from longitudinal mixed models. Women with hysterectomy (those with and without an ovarian estrogen source or using HT) also had a significantly greater annual decline in velocity and perceived physical functioning compared with the referent group (Figs. 1 and 2, Table 3). They had reduced levels of functioning and greater rates of change in the 2-lb lift (P<.005), sit-to-stand (P<.01), timed stair climb (P<.01), timed walk (P<.01), velocity (P<.05), and perception of physical functioning (P<.01).
Women who were naturally postmenopausal and without HT took longer to lift 2 lb and had less grip strength after adjustment for time, BMI, and smoking in comparison to premenopausal and perimenopausal women (see Table 3). Level of functioning among postmenopausal women with exogenous hormone replacement was similar to premenopausal women on eight of nine physical functioning measures. Diminished functioning in postmenopausal women was observed in hand grip (P<.005), 2-lb lift (P<.05), sit-to-stand (P<.05), velocity (P<.05), and perceived physical functioning (P<.05). In addition, women who were naturally postmenopausal and without HT walked with less velocity and perceived themselves as having more functional loss after adjustment for time, BMI, and smoking in comparison with premenopausal and perimenopausal women (see Table 3, Figs. 1 and 2).
Almost universally, assessment of physical functioning has been associated with describing diminished capacity in elder health. Typically, female participants have been characterized as having more functional limitation than males,18 experiencing a greater rate of decline in physical functioning and less likelihood of recovery from disability.19 Although two studies included women aged 51–61 years18 and 65 years or older,19 they did not consider the contribution of the menopause transition to the decline in physical functioning. In this longitudinal assessment of women at mid life, information from both interview and performance-based measures of physical functioning showed an increasing vulnerability with time as women age and traverse some aspects of the menopause transition, particularly hysterectomy.
Women at mid life were selected for study in anticipation that this time period represented a critical node for change in health status with aging. Although there was evidence of increasing compromise with time, as shown in the statistically significant regression coefficients associated with calendar time in the mixed longitudinal models, we specifically evaluated whether elements of the menopause transition contributed to decline in functioning apart from time. We had previously reported that the menopausal transition was associated with lower levels of physical functioning10; however, those findings were based on a cross-sectional survey, a design that precluded temporal or causal inferences and that did not include performance-based measures.
Hysterectomy was associated with statistically significant loss of physical functioning over a 5-year period in women at mid life. These losses were observed in both the performance-based measures as well as in the perception of physical functioning. The effect of hysterectomy was still evident even after considering estrogen contribution from ovarian conservation or exogenous hormone use. The observation of more compromise in performance-based physical functioning was corroborated by women's self-assessment of their overall health status. More than 20% of women with hysterectomy and no HT described their health as fair or poor whereas in the group of premenopausal and perimenopausal women, only 5% described their health as fair or poor.
The compromise in level of physical functioning occurring in those with hysterectomy may reflect the effect of the events that gave rise to the hysterectomy, the type of surgical procedure, or the effect from an abrupt alteration in hormone levels associated with surgery. Medical records were available for approximately 70% of the procedures reported, and we took the very conservative approach of censoring data from those women reporting surgery but for whom we were unsuccessful in securing medical records. Although procedures had changed somewhat over time, only a small fraction of procedures were laparoscopic. We considered whether removal of ovaries would result in alterations in estradiol and testosterone concentrations that could affect muscle mass and strength20 or lead to a shift in the collagen types in cartilage, ligaments, and skin.21–23 The similarity in physical functioning loss among women who did or did not retain exposure to an estrogen source through ovarian conservation or exogenous use suggests that having the surgical procedure is the more likely explanation for the diminished functioning.
In addition to the loss among women with hysterectomy, there was also loss among the postmenopausal women without hormone use. These losses were substantially less than those observed in women with hysterectomy, both in the number of tasks that reflected compromise and in the magnitude of the regression coefficients from the mixed models. It is noteworthy that among the postmenopausal women, there was substantial loss of hand grip strength, a factor not seen in other groups. Postmenopausal women using HT had regression coefficients for amount of physical functioning change that were not significantly different from those of the premenopausal and perimenopausal women.
The greater functional decline observed in women with hysterectomy was found in multiple measures selected to integrate a variety of functioning domains. The time to climb up and down stairs has been used as a performance-based measure of functional status of older adults.24 Stair climbing requires strength; large-joint torque at weight-bearing joints is considerably higher in stair climbing than during walking.25 Stair ascent and descent also requires dynamic balance control, because the body weight is controlled from a single support limb during swing. Grip and pinch strength are used as clinical indicators of strength and dexterity. Sit-to-stand is a task that requires an individual to transfer from a stable position on the chair seat to a much less stable position in upright stance. The task also requires substantial strength, especially of the knee extensor muscles,26,27 to accelerate the body upward. An important, consistently reported difference between the gait patterns of young and old walkers is a decrease in walking velocity and stride length and an increase in double-stance time in older walkers.28,29 Not only does the time required to walk increase with age but also the pattern of joint coordination changes; when and how these transitions occur is not known.
This study has notable strengths and limitations. It is a population-based study conducted with very good long-term retention, resulting in less likelihood of bias due to loss to follow-up. Although the population is younger than is typically reported in research on physical functioning, results are also less likely to reflect morbid and mortal disease events that could contribute to biased findings in the follow-up period. Obviously, the level and rate of change in functioning in this population does not reflect a “frail” subgroup, terminology frequently applied to those who are elderly and functionally limited. Rather, the group with more limitations may reflect an underlying vulnerability that, with time, could predispose them to less successful aging. Given the limited number of studies in this age group, it is important that the study be replicated.
In summary, we identified that in white women at mid life, those with hysterectomy were more vulnerable to having lower levels of physical functioning status as well as a greater decline in functioning. These negative characteristics persisted in women using HT. There was some evidence of more physical limitation in the postmenopausal women compared with the premenopausal women; but differences were more consistent, more frequent, and of greater magnitude among those with hysterectomy. If these findings are confirmed, it suggests that hysterectomy can lead to characteristics associated with greater “aging” and efforts should be expended to ameliorate those characteristics in addressing the long-term quality of life in these women. Hysterectomy, even with availability of an estrogen source, appears to be a “risk” state for diminishing physical function at mid life, and this may initiate a vulnerable stage for future compromised quality of life.
1. Chang M, Cohen-Mansfield J, Ferrucci L, Leveille S, Volpato S, de Rekeneire N, et al. Incidence of loss of ability to walk 400 meters in a functionally limited older population. J Am Geriatr Soc 2004;52:2094–8.
2. Verbrugge LM, Jette AM. The disablement process. Soc Sci Med 1994;38:1–14.
3. Freedman V, Martin L. Understanding trends in functional limitations among older Americans. Am J Public Health 1998;88:1457–62.
4. Fried TR, Bradley EH, Williams C, Tinetti ME. Functional disability and health care expenditures for older persons. Arch Intern Med 2001;161:2602–7.
5. Guralnik JM, Ferrucci L. Assessing the building blocks of function: utilizing measures of functional limitation. Am J Prev Med 2003;25 suppl:112–21.
6. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 1995;332:556–61.
7. Liao Y, McGee DL, Cao G, Cooper RS. Recent changes in the health status of the older U.S. population: findings from the 1984 and 1994 supplement on aging. J Am Geriatr Soc 2001;49:443–9.
8. Lubitz J, Cai L, Kramarow E, Lentzner H. Health, life expectancy, and health care spending among the elderly. N Engl J Med 2003;349:1048–55.
9. Minkler M, Fuller-Thomson E, Guralnik JM. Gradient of disability across the socioeconomic spectrum in the United States. N Engl J Med 2006;355:695–703.
10. Sowers M, Pope S, Welch G, Sternfeld B, Albrecht G. The association of menopause and physical functioning in women at midlife. J Am Geriatr Soc 2001;49:1485–92.
11. Fuh JL, Wang SJ, Lee SJ, Lu SR, Juang KD. Quality of life and menopausal transition for middle-aged women on Kinmen island. Qual Life Res 2003;12:53–61.
12. Sowers M, Crutchfield M, Bandekar R, Randolph JF, Shapiro B, Schork MA, et al. Bone mineral density and its change in pre- and perimenopausal white women: the Michigan Bone Health Study. J Bone Miner Res 1998;13:1134–40.
13. Ware JE Jr, Sherbourne CD. The MOS 36-item Short-form Health Survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.
14. Brazier JE, Harper R, Jones NM, O'Cathain A, Thomas KJ, Usherwood T, et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ 1992;305:160–4.
15. McHorney CA, Ware JE Jr, Raczek AE. The MOS 36-item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993;31:247–63.
16. McHorney CA, Ware JE Jr, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care 1994;32:40–66.
17. Goodpaster BH, Carlson CL, Visser M, Kelley DE, Scherzinger A, Harris TB, et al. Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study. J Appl Physiol 2001;90:2157–65.
18. Clark DO, Stump TE, Wolinsky FD. Predictors of onset of and recovery from mobility difficulty among adults aged 51–61 years. Am J Epidemiol 1998;148:63–71.
19. Beckett LA, Brock DB, Lemke JH, Mendes de Leon CF, Guralnik JM, Fillenbaum GG, et al. Analysis of change in self-reported physical function among older persons in four population studies. Am J Epidemiol 1996;143:766–78.
20. Taaffe DR, Sipilä S, Cheng S, Puolakka J, Toivanen J, Suominen H. The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention. Clin Physiol Funct Imaging 2005;25:297–304.
21. Brincat MP, Baron YM, Galea R. Estrogens and the skin. Climacteric 2005;8:110–23.
22. Richette P, Corvol M, Bardin T. Estrogens, cartilage, and osteoarthritis. Joint Bone Spine 2003;70:257–62.
23. Sowers MR, McConnell D, Jannausch M, Buyuktur AG, Hochberg M, Jamadar DA. Estradiol and its metabolites and their association with knee osteoarthritis. Arthritis Rheum 2006;54:2481–7.
24. West SK, Rubin GS, Munoz B, Abraham D, Fried LP. Assessing functional status: correlation between performance on tasks conducted in a clinic setting and performance on the same task conducted at home. The Salisbury Eye Evaluation Project Team. J Gerontol A Biol Sci Med Sci 1997;52:M209–17.
25. Andriacchi TP, Andersson GB, Fermier RW, Stern D, Galante JO. A study of lower-limb mechanics during stair-climbing. J Bone Joint Surg Am 1980;62:749–57.
26. Rodosky MW, Andriacchi TP, Andersson GB. The influence of chair height on lower limb mechanics during rising. J Orthop Res 1989;7:266–71.
27. Hughes MA, Myers BS, Schenkman ML. The role of strength in rising from a chair in the functionally impaired elderly. J Biomech 1996;29:1509–13.
28. Winter DA, Patla AE, Frank JS, Walt SE. Biomechanical walking pattern changes in the fit and healthy elderly. Phys Ther 1990;70:340–7.
29. Murray MP, Kory RC, Clarkson BH. Walking patterns in healthy old men. J Gerontol 1969;24:169–78.