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SSRIs for Vasomotor Symptoms and Bone Health

Recent research has indicated that selective serotonin reuptake inhibitors (SSRIs) may be an effective option for the treatment of vasomotor symptoms associated with menopause. However, it has been documented in some recent observational studies that SSRIs are associated with an increased risk of bone loss in older patients (2, 4). Since postmenopausal women are already at risk for bone loss and osteoporosis based on age and biological sex, taking an SSRI for vasomotor symptoms or depression and potentially adding additional risk for osteoporosis is a valid concern. To date, no precise mechanism of SSRI-induced bone loss has been determined, but in vitro and animal studies have suggested that serotonin and serotonin transporters play a role in bone health.

One major limitation seen across much of the literature is the inability to separate the effects of the medication (SSRIs) from the effects of the illness (depression) on bone health. In attempt to decipher the direct effect of SSRIs on bone health without depression as a confounding variable, a recent study was conducted to evaluate the effects of escitalopram treatment on markers in bone turnover in peri- or postmenopausal nondepressed women (3).

In this 8-week, placebo-controlled, double-blind multicenter trial, nondepressed women were given 10-20 milligrams of escitalopram or placebo for the treatment of menopausal vasomotor symptoms. Bone mineral density is typically the gold standard for measuring bone health; however, the length of the study would not allow for notable changes in this measure. Thus, more dynamic measures of bone health were examined. Procollagen type 1 amino-terminal propeptide (P1NP) and carboxy-terminal collagen crosslinks (CTX) were used as markers of bone formation and resorption (loss), respectively.

Escitalopram did not differ from placebo with regard to levels of  P1NP and CTX, two markers of bone turnover.  Specifically, serum P1NP decreased by 1.02 ng/mL in those taking escitalopram and by 1.88 ng/mL in those taking a placebo (p=0.65). Serum CTX decreased by 0.02 ng/mL in those taking escitalopram and by 0.00 ng/mL in those taking a placebo (p=0.24).

Overall, the results suggest that escitalopram does not significantly alter bone metabolism in the short term in nondepressed peri- and postmenopausal women. However, according to data from the Study of Women’s Health Across the Nation, women experience vasomotor symptoms for an average of 7.4 years (1). Thus, while the findings of this study are reassuring, we do not know if the results from an 8-week study would be the same for women who must take SSRIs for many years for the treatment of menopausal vasomotor symptoms.

Nonetheless SSRIs might be the best option for perimenopausal women with vasomotor symptoms, especially in those with comorbid anxiety or depression.  If SSRI treatment for vasomotor symptoms is deemed appropriate, women with other risk factors for osteoporosis should consider trying to balance this risk through preventive interventions like resistance or weight bearing exercise.

Alexandra Sosinsky, BS

  1. Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, Hess R, Joffe H, Kravitz HM, Tepper PG,Thurston RC. Duration of menopausal vasomotor symptoms over the menopause transition. Arch Intern Med. 2015: 175(4):531-9.
  1. Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE. Use of antidepressants and rates of hip bone loss in older women.  Arh Intern Med. 2007:167:1240-1245.
  1. Diem SJ, Joffe H, Larson JC, Tsai JN, Guthrie KA, LaCroix AZ, Ensrud KE, Freeman EW, Leder BZ. Effects of escitalopram on markers of bone turnover: a randomized clinical trial. J Clin Endocrinol Metab. 2014:99(9):E1732-7.
  1. Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, Orwoll E, Bliziotes MM. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007: 167:1246-1251.


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