The Role of Vitamin D in Menopause: Relationship to Menopausal Symptoms in Body Composition
Condition: Hot Flushes; Menopause, Premature; Obesity; Vitamin D Deficiency
MeSH terms: Menopause, Premature; Primary Ovarian Insufficiency; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 1

Summary: 
      Specific Aim 1: To compare effects of Vitamin D supplementation to usual care on symptoms in
      women transitioning to early postmenopause and determine the associated effect size in order
      to conduct a power analysis for a future RCT. Hypothesis: Vitamin D insufficient women in
      early postmenopause who are randomized to supplementation, titrated to achieve sufficiency
      for 2 months, will have fewer symptoms including hot flashes, mood, and musculoskeletal
      complaints than women randomized to usual care.

      Specific Aim 2: To compare effects of Vitamin D supplementation to usual care on body
      composition (by dual-energy x-ray absorptiometry [DXA] and by weight, BMI, waist to hip
      ratio) in overweight/obese women transitioning to early postmenopause and determine the
      associated effect size for a power analysis for a future RCT. Hypothesis: Vitamin D
      insufficient women in the menopausal transition randomized to supplementation, titrated to
      achieve sufficiency for 9 months, will improve DXA body composition (less total body and
      abdominal fat), compared to women in usual care, who will have increased body weight,
      including total and abdominal fat.

      Specific Aim 3: To estimate the proportion of overweight/obese middle-aged women who achieve
      sufficiency by 1 month versus 2 or more months and to determine if achieving sufficiency by 1
      month varies by baseline characteristics. Hypothesis: About 80% of participants will achieve
      sufficient Vitamin D level by 1 month. Those who need more than 1 month for sufficiency will
      have lower baseline levels and higher initial BMI.
    

Detailed description: 
      It is increasingly recognized that Vitamin D deficiency affects more than just bone health.
      Links between Vitamin D deficiency have been established or purported for diabetes, the
      metabolic syndrome, cardiovascular disease, and cancer. We propose to explore if Vitamin D
      replacement (safe, readily available, and inexpensive) has beneficial effects on 2 novel
      outcomes in early postmenopausal women: menopause-related symptoms and body composition.

      Most women transitioning through menopause, especially those with higher percent body fat,
      will experience hot flashes through a mean of 4 to 5 years. Many also have mood disturbances
      and muscle aches although the link with the menopausal transition is less clear. In many,
      these symptoms are severe enough to negatively impact their quality of life, work
      performance, and interpersonal relationships. Current treatments for menopause-related
      symptoms, such as menopausal hormone therapy, antidepressants, and anticonvulsants, have
      significant side effects and serious long term adverse consequences and symptoms recur after
      treatment discontinuation. A safe, inexpensive, well-tolerated treatment is therefore of high
      priority.

      Both our preliminary data in early postmenopausal women and a 2010 publication of women on
      aromatase inhibitors for breast cancer show an association between Vitamin D deficiency and
      menopause-related symptoms including hot flashes. It is postulated that a contributor to hot
      flashes is a menopausal decline in serotonin, a neurotransmitter with known effects on
      thermoregulation. As Vitamin D can protect against experimental serotonin depletion in rats,
      one proposed mechanism for symptom alleviation is prevention of serotonin decline in
      menopause.

      Both Vitamin D deficiency and the menopausal transition are associated with mood disturbances
      and musculoskeletal aches. Because estrogen increases the activity of the enzyme responsible
      for activating Vitamin D, the fall in estrogen that occurs during the menopausal transition
      could uncover previously subclinical Vitamin D deficiency. Indeed, Vitamin D can improved
      mood and muscle aches in non-menopausal populations, but its effects in menopausal women,
      where the benefits may be magnified, have not been previously studied.
    

Intervention name(s): Vitamin D; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): We will administer 100,000 IU Vitamin D3 orally as an observed 1-time bolus and then prescribe 1000 IU by mouth daily. These doses have achieved sufficiency in other populations.99, 100 We will use the level of sufficiency (≥30 ng/ml [≥75 nmol/L]) that is recommended by most experts in the field.89-91, 93, 95, 96, 101-105 We will repeat the bolus at 1 month if the target level is not achieved. The control group will receive matching placebo and a similar proportion will go through a dummy titration. All women consuming less than 800 mg/day of calcium (by dietary history) will receive 500 mg of calcium to ensure sufficiency.; Current standard of practice does not dictate that otherwise healthy early menopausal women have Vitamin D levels evaluated. Women with Vitamin D levels between 10 and 29 ng/ml who receive placebo will be receiving usual care (i.e., no additional Vitamin D repletion above intake at the time of screening).
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Health Services Research
Keywords: Vitamin D; Obesity; Menopause; Hot Flashes