Menopause: The Journal of The North American Menopause Society Vol. 22, No. 7, pp. 797/799 DOI: 10.1097/gme.0000000000000478 * 2015 by The North American Menopause Society
LETTERS
TO THE
EDITOR
To the Editor: Vitamin D is currently a hot issue for physicians and the public. Vitamin D level is closely correlated with bone health, and many recent reports on 25-hydroxyvitamin D [25(OH)D] levels and cardiovascular disease, inflammation, depression, cancer, pelvic pain, and other conditions have been published. Physicians who treat postmenopausal women reporting sleep disturbances, emotional depression, or chronic fatigue are curious about whether adding vitamin D supplementation to hormone therapy would lead to a synergistic effect on relieving these symptoms. After vitamin D supplementation and hormone therapy had been prescribed to women with serum 25(OH)D levels indicative of vitamin D deficiency, some reported a decrease in menopause-related symptoms. LeBlanc et al1 concluded that there is no evidence linking 25(OH)D levels and menopauserelated symptoms in postmenopausal women. They also hypothesized that estrogen increases the activity of the enzyme responsible for activating vitamin D; we agree with their hypothesis. Administration of estradiol increases the expression of estrogen receptor (which maintains bone strength and bone health) and vitamin D.2 Vitamin D stimulates estradiol biosynthesis in ovaries and in cells pretreated with noncalcemic analogs, which increases the expression of estrogen receptor-> protein.3 What exactly increases the synergistic effect of estrogen and vitamin D? Why are there differences (including ethnic differences) in improvement of menopausal symptoms with vitamin D and hormone therapy among women? We believe that vitamin D affects estrogen levels and that estrogen levels also affect vitamin D levels. We have hypothesized that the vitamin D receptor (VDR) itself and VDR genetic polymorphisms have different effects on women. VDR is a member of a superfamily of nuclear receptors; it mediates the actions of vitamin D. Membrane signaling can be correlated with nongenomic effects of VDR; correlations and effects of vitamin D levels on diseases and conditions such as cancer, immunity, bone pain, cardiovascular disease, and depression have been reported. However, reports on potential effects of VDR on diseases are rare. Another hypothesis is that VDR gene polymorphisms affect menopause-related symptoms. Postmenopausal women and their physicians want evidence-based data on whether levels of vitamin D and estrogen have a synergistic effect on menopauserelated symptoms or other conditions. Therefore, further research on VDR gene polymorphisms and the relationship between VDR or serum vitamin D levels and health conditions, including menopausal symptoms, should be performed.
Funding/support: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2014R1A1A3049819).
Financial disclosure/conflicts of interest: None reported.
Tae-Hee Kim, MD, PhD Hae-Hyeog Lee, MD, PhD Department of Obstetrics and Gynecology Soonchunhyang University College of Medicine Bucheon, Republic of Korea Jun-Mo Kim, MD, PhD Department of Urology Soonchunhyang University College of Medicine Bucheon, Republic of Korea
REFERENCES 1. LeBlanc ES, Desai M, Perrin N, et al. Vitamin D levels and menopauserelated symptoms. Menopause 2014;21:1197-1203. 2. Kim TH, Lee HH, Jeon DS, Byun DW. Compression fracture in postpartum osteoporosis. J Bone Metab 2013;20:115-118. 3. Somjen D, Kohen F, Gayer B, et al. A non-calcemic vitamin D analog modulates both nuclear and putative membranal estrogen receptors in cultured human vascular smooth muscle cells. J Steroid Biochem Mol Biol 2004;89-90:397-399.
To the Editor: In a recent issue of this journal, Wang et al1 reported on the prevalence of nonalcoholic fatty liver disease (NAFLD) and its metabolic risk factors in women of different ages and body mass indexes (BMIs). They stated that obese and postmenopausal women have a high prevalence of NAFLD and severe metabolic disorders and that the prevalence of nonalcoholic steatohepatitis (NASH) is increased in this patient group. Although we appreciate their great contribution to answering an important question regarding the prevalence of NAFLD and NASH in a large series of women of different ages and BMIs, some methodologic points in their well-written article require further clarification and discussion. Although a variety of noninvasive tests have demonstrated reasonable ability to predict the presence of advanced disease with NASH and fibrosis, BAAT (BMI, age, alanine aminotransferase, and triglycerides) score is the least used method for this assessment. BAAT index is calculated as the sum of four distinct variables: BMI, age, alanine aminotransferase, and triglycerides. A score of 0 or 1 has a sensitivity of 100%, a specificity of 45%, and a negative predictive value of 100%; a score of 4 has only 14% sensitivity for the diagnosis of septal fibrosis and cirrhosis.2,3 In other words, the presence of one factor (or the absence of factors) excludes septal fibrosis or cirrhosis in women with NAFLD, but a lack of elevated scores does not rule out advanced fibrosis. In fact, Ratziu et al,4 who first proposed BAAT score, replaced this test with FibroTest-FibroSURE because of the low sensitivity of the Menopause, Vol. 22, No. 7, 2015
Copyright © 2015 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
797
LETTERS
TO THE
EDITOR
To the Editor: Vitamin D is currently a hot issue for physicians and the public. Vitamin D level is closely correlated with bone health, and many recent reports on 25-hydroxyvitamin D [25(OH)D] levels and cardiovascular disease, inflammation, depression, cancer, pelvic pain, and other conditions have been published. Physicians who treat postmenopausal women reporting sleep disturbances, emotional depression, or chronic fatigue are curious about whether adding vitamin D supplementation to hormone therapy would lead to a synergistic effect on relieving these symptoms. After vitamin D supplementation and hormone therapy had been prescribed to women with serum 25(OH)D levels indicative of vitamin D deficiency, some reported a decrease in menopause-related symptoms. LeBlanc et al1 concluded that there is no evidence linking 25(OH)D levels and menopauserelated symptoms in postmenopausal women. They also hypothesized that estrogen increases the activity of the enzyme responsible for activating vitamin D; we agree with their hypothesis. Administration of estradiol increases the expression of estrogen receptor (which maintains bone strength and bone health) and vitamin D.2 Vitamin D stimulates estradiol biosynthesis in ovaries and in cells pretreated with noncalcemic analogs, which increases the expression of estrogen receptor-> protein.3 What exactly increases the synergistic effect of estrogen and vitamin D? Why are there differences (including ethnic differences) in improvement of menopausal symptoms with vitamin D and hormone therapy among women? We believe that vitamin D affects estrogen levels and that estrogen levels also affect vitamin D levels. We have hypothesized that the vitamin D receptor (VDR) itself and VDR genetic polymorphisms have different effects on women. VDR is a member of a superfamily of nuclear receptors; it mediates the actions of vitamin D. Membrane signaling can be correlated with nongenomic effects of VDR; correlations and effects of vitamin D levels on diseases and conditions such as cancer, immunity, bone pain, cardiovascular disease, and depression have been reported. However, reports on potential effects of VDR on diseases are rare. Another hypothesis is that VDR gene polymorphisms affect menopause-related symptoms. Postmenopausal women and their physicians want evidence-based data on whether levels of vitamin D and estrogen have a synergistic effect on menopauserelated symptoms or other conditions. Therefore, further research on VDR gene polymorphisms and the relationship between VDR or serum vitamin D levels and health conditions, including menopausal symptoms, should be performed.
Funding/support: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2014R1A1A3049819).
Financial disclosure/conflicts of interest: None reported.
Tae-Hee Kim, MD, PhD Hae-Hyeog Lee, MD, PhD Department of Obstetrics and Gynecology Soonchunhyang University College of Medicine Bucheon, Republic of Korea Jun-Mo Kim, MD, PhD Department of Urology Soonchunhyang University College of Medicine Bucheon, Republic of Korea
REFERENCES 1. LeBlanc ES, Desai M, Perrin N, et al. Vitamin D levels and menopauserelated symptoms. Menopause 2014;21:1197-1203. 2. Kim TH, Lee HH, Jeon DS, Byun DW. Compression fracture in postpartum osteoporosis. J Bone Metab 2013;20:115-118. 3. Somjen D, Kohen F, Gayer B, et al. A non-calcemic vitamin D analog modulates both nuclear and putative membranal estrogen receptors in cultured human vascular smooth muscle cells. J Steroid Biochem Mol Biol 2004;89-90:397-399.
To the Editor: In a recent issue of this journal, Wang et al1 reported on the prevalence of nonalcoholic fatty liver disease (NAFLD) and its metabolic risk factors in women of different ages and body mass indexes (BMIs). They stated that obese and postmenopausal women have a high prevalence of NAFLD and severe metabolic disorders and that the prevalence of nonalcoholic steatohepatitis (NASH) is increased in this patient group. Although we appreciate their great contribution to answering an important question regarding the prevalence of NAFLD and NASH in a large series of women of different ages and BMIs, some methodologic points in their well-written article require further clarification and discussion. Although a variety of noninvasive tests have demonstrated reasonable ability to predict the presence of advanced disease with NASH and fibrosis, BAAT (BMI, age, alanine aminotransferase, and triglycerides) score is the least used method for this assessment. BAAT index is calculated as the sum of four distinct variables: BMI, age, alanine aminotransferase, and triglycerides. A score of 0 or 1 has a sensitivity of 100%, a specificity of 45%, and a negative predictive value of 100%; a score of 4 has only 14% sensitivity for the diagnosis of septal fibrosis and cirrhosis.2,3 In other words, the presence of one factor (or the absence of factors) excludes septal fibrosis or cirrhosis in women with NAFLD, but a lack of elevated scores does not rule out advanced fibrosis. In fact, Ratziu et al,4 who first proposed BAAT score, replaced this test with FibroTest-FibroSURE because of the low sensitivity of the Menopause, Vol. 22, No. 7, 2015
Copyright © 2015 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
797
