Musculoskeletal Syndrome of Menopause in Women

Nov 20

Menopause is the period during midlife when the production of estrogen decreases and ultimately stops. Approximately 2 million women in the US and more than 47 million women worldwide will enter menopause annually with this transition occurring between the ages of 45 to 55 years with a duration of symptoms lasting anywhere from 2 to 10 years (1). More than 35 symptoms are known to be associated with menopause, including hot flashes, sleep disturbances, anxiety, and loss of libido; however, musculoskeletal syndrome of menopause is less commonly recognized by healthcare providers and can be devastating unless addressed. More than 70% will experience musculoskeletal symptoms and 25% will be disabled by them through the transition from perimenopause to postmenopause yet 40% will have no structural findings following diagnostic workup (2). The musculoskeletal syndrome of menopause includes but is not limited to musculoskeletal pain, arthralgia (joint pain), loss of lean muscle mass, loss of bone density, increased tendon and ligament injury, adhesive capsulitis (frozen shoulder), progression of osteoarthritis and metabolic dysfunction (hypercholesterolemia, insulin resistance). The musculoskeletal syndrome of menopause may have a profound negative impact on the quality of life of postmenopausal women.

The National Institutes of Health defines menopause as a point in time 12 months after a woman’s last period and perimenopause as the years leading up to that point when women have changes in their monthly cycles, hot flashes or other symptoms. The average age for onset of perimenopause is 47.5, while the average age of menopause is 52.6 with Hispanics having an onset about 2 years earlier (3). For most women, perimenopause results in 10% reduction in bone mineral density (4) and a 0.6% reduction in muscle mass per year after menopause (5). This musculoskeletal disorder is caused by the precipitous decline in estradiol, the most biologically active form of estrogen, which impacts nearly all types of musculoskeletal tissue including muscle, bone, cartilage, tendon, adipose and ligament (6, 7). The fall in estradiol levels leads to five major changes: 1) Increased inflammation 2) sarcopenia (muscle loss) 3) progression of osteoarthritis with increased joint pain and 4) Decrease in bone density (osteoporosis). Let’s take a closer look at each and why hormone replacement therapy may be helpful for some perimenopausal or postmenopausal women.

Inflammation

More than half of perimenopausal women report joint pain symptoms (8,9). Estrogen is an important inflammatory modulator that can affect generalized joint pain. As women progress through the menopause transition and into the postmenopause phase, musculoskeletal pain increases and often without radiographic findings (x-ray or MRI) to explain the pain. The regulation of inflammation occurs through estradiol. Estrogen is a potent anti-inflammatory mediator, helping to regulate our immune system through modulation of pro-inflammatory signaling molecules (10,11). One important inflammatory molecule that estrogen inhibits is TNF-alpha (12). TNF-alpha has been shown to degrade muscle proteins and reduce the ability of the adult muscle to respond to damage (13). This can directly impact musculoskeletal healing and a woman's ability to recover from musculoskeletal injuries. Furthermore, TNF-alpha that is released by adipose cells impairs muscle function (14-16), negatively impacting a woman’s ability to maintain a functional musculoskeletal system. Therefore, one way postmenopausal women can help to naturally lower pain and inflammation is through HRT (hormone replacement therapy).

Muscle Loss

Sarcopenia is the age-related progressive loss of muscle mass and strength. The main symptom of the condition is muscle weakness and it is characterized by loss of type II muscle fibers which are the muscle fibers that generate power and force. Sarcopenia is a major factor in frailty, falls and fractures. Most notably, postmenopausal women experience a rapid decrease in muscle mass and strength and, therefore, are vulnerable to age-related frailty. Although nutritional interventions such as increasing protein intake and vitamin D combined with resistance strength training has shown to improve muscle mass and strength, estrogen has also been shown to be an important factor in maintaining muscle mass and strength. Studies have shown that decreased levels of estrogen can impair mitochondrial function and reduce insulin sensitivity in skeletal muscle (17,18) and that 6 months of estrogen deficiency can lead to 10% decrease in strength and 18% decrease in muscle volume (19).

When women are placed on HRT (hormone replacement therapy), there is evidence that estrogen helps to increase lean muscle mass (20,21), especially when used in conjunction with strength training (22,23). HRT can help increase sensitivity to anabolic stimuli such as with resistance training and lead to an increase in protein synthesis (24). In a 2005 study looking at postmenopausal women, those who were on hormone replacement therapy with estrogen had a statistically significant increase in both muscle cross sectional area and grip strength as compared to those not on estrogen therapy (25).

Osteoarthritis

Although progression of osteoarthritis can be due to many factors, it is known that the osteoarthritis incidence significantly increases around the time of menopause. Furthermore, studies report that women often experience more severe arthritic pain than men (26,27) and postmenopausal decrease in estrogen is associated with increased rate of hip, knee and finger arthritis. Use of HRT in postmenopausal women to slow the progression or treat osteoarthritis pain is debatable but there is some evidence that estrogen is protective against connective tissue and cartilage degeneration (28)

Osteoporosis

Osteoporosis is a serious health problem worldwide for many postmenopausal women and decreased bone density places women at increased risk for fractures in the spine, hip and wrist. More than 70% of hip fractures occur in women and osteoporotic fractures are very harmful since they often lead to chronic pain, disability and sometimes even death (29). As discussed earlier, estrogen deficiency is associated with significant bone loss, increased fragility and risk of fracture. Prevention of osteoporosis includes proper nutrition and weight bearing exercise such as resistance training, walking or jogging. HRT (hormone replacement therapy) has also been shown to reduce the risk as well as the incidence of osteoporotic fractures in postmenopausal women (30). Therefore, HRT should be indicated for the prevention and treatment of osteoporotic fractures due to its effectiveness and safety.

Most women who are perimenopausal or postmenopausal are candidates for HRT. Generally speaking, benefits from HRT are greater in women who start HRT earlier within their postmenopausal phase (ten years or less). Some contraindications to HRT include history of unexplained vaginal bleeding, estrogen-sensitive breast and endometrial cancers, history or blood clots or stroke.