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Gas transfer in the female lung varies over the menstrual cycle in parallel with the cyclic angiogenesis that occurs in the uterine endometrium. Given that vessels form and regress in the uterus under the control of hormones, angiogenic factors and pro-angiogenic circulating bone marrow-derived progenitor cells, we tested the possibility that variation in pulmonary gas transfer over the menstrual cycle is related to a systemic cyclic pro-angiogenic state that influences lung vascularity. Women were evaluated over the menstrual cycle with weekly measures of lung diffusing capacity and its components, the pulmonary vascular capillary bed and membrane diffusing capacity, and their relation to circulating CD34 + CD133 + progenitor cells, hemoglobin, factors affecting hemoglobin binding affinity, and pro-angiogenic factors. Lung diffusing capacity varied over the menstrual cycle, reaching a nadir during the follicular phase following menses. The decline in lung diffusing capacity was accounted for by ~25% decrease in pulmonary capillary blood volume. In parallel, circulating CD34 + CD133 + progenitor cells decreased bỹ 24%, and were directly related to angiogenic factors, and to lung diffusing capacity and pulmonary capillary blood volume. The finding of greater number of lung microvessels in ovariectomized female mice receiving estrogen as compared to placebo verified that pulmonary vascularity is influenced by hormonal changes. These findings suggest that angiogenesis in the lungs may participate in the cyclic changes in gas transfer that occur over the menstrual cycle.

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Phantom limb pain is a common consequence of limb amputation and is prevalent among the service members sustaining traumatic battlefield limb injuries during the conflicts in Iraq and Afghanistan. Current treatment to relieve phantom limb pain consists of physical, behavioral, and medical modalities including opioids and adjunct medications. Treatment failure resulting in persistent pain and disability may result. This case series describes four previously healthy service members who developed phantom limb pain following traumatic amputation successfully treated with buprenorphine/naloxone after failing traditional treatment. This is the first reported case series of patients expressing improved pain control with decreased frequency of phantom limb pain with the use of buprenorphine/naloxone instead of traditional opioid agonists.