We thank Drs. Eng and Quraishi1 for their thoughtful comments on our paper investigating the effects of short-term nasal continuous positive airway pressure (nCPAP) therapy on serum vitamin D, parathormone, and calcium levels in severe obstructive sleep apnea (OSA) patients.2 We found that only in male OSA patients who appropriately use nCPAP therapy for a 1-week period (≥ 4 hours per night, mean residual apnea-hypopnea index < 5 per hour, OSA-R) vitamin D increased to adequate serum levels. Surprisingly, female OSA-R patients did not show changes in serum vitamin D concentrations after nCPAP treatment.
In their letter, Dr. Eng and Dr. Quraishi suggested that vitamin D serum levels didn't change in female OSA-R patients due to the reciprocal interactions between estrogens and inflammatory markers affecting vitamin D homeostasis.1 Accordingly, authors based their assumption on the evidence that serum vitamin D levels may be negatively regulated by inflammation, which may be in turn modified by estrogens levels.3,4 However, they evidenced two specific conditions: in presence of adequate endogenous estrogen production, and during exogenous estrogen therapy.1
In our paper, we hypothesized that vitamin D serum levels were not modified by nCPAP therapy in female OSA-R group because of the mediation of female sexual hormones.2 Indeed, estrogens negatively influence vitamin D homeostasis, particularly in postmenopausal women.5 In our study female OSA-R group was prevalently constituted by postmenopausal women, since OSA is more frequent in those patients.6 Moreover, the female OSA-R group did not count patients taking exogenous estrogens therapy. On these basis, we concluded that in female OSA-R patients reduced estrogen levels, not changing after nCPAP therapy,6 did not allow the recovery of serum vitamin D concentrations.
Therefore, although the hypothesis from Dr. Eng and Dr. Quraishi is interesting, it is not applicable to our study for two reasons: firstly, our cohort of female OSA-R patients did not show adequate estrogen production due to postmenopausal condition; secondly, female OSA-R group did not count patients taking exogenous estrogen therapy.
In conclusion, taking into account that in female OSA patients the effect of nCPAP therapy is lowered due to hormonal and genetic factors,7 we agree with Eng and Quraishi in suggesting future studies interrogating the effect of inflammatory markers coupled with sexual hormones changes in altering micronutrient status in OSA patients, especially women.
This was not an industry supported study. The authors have indicated no financial conflicts of interest.
Liguori C, Romigi A, Izzi F, Mercuri NB, Marciani MG, Placidi F. Estrogen deficiency hampers the beneficial effect of continuous positive airway pressure therapy on serum vitamin D concentrations in postmenopausal women affected by obstructive sleep apnea. J Clin Sleep Med 2015;11(12):1473–1474.
Eng KJ, Quraishi SA, authors. Changes in vitamin D status after nasal continuous positive airway pressure: could alterations in systemic inflammatory markers explain these observations? J Clin Sleep Med. 2015;11:1471.
Liguori C, Romigi A, Izzi F, et al., authors. Continuous positive airway pressure treatment increases serum vitamin D levels in male patients with obstructive sleep apnea. J Clin Sleep Med. 2015;11:603–7. [PubMed]
Mellenthin L, Wallaschofski H, Grotevendt A, Völzke H, Nauck M, Hannemann A, authors. Association between serum vitamin D concentration and inflammatory markers in the general adult population. Metabolism. 2014;63:1056–62. [PubMed]
Davison S, Davis S, authors. New markers for cardiovascular disease risk in women: impact of endogenous estrogen status and exogenous postmenopausal hormone therapy. J Clin Endocrinol Metab. 2003;88:2470–8. [PubMed]
Lerchbaum E, author. Vitamin D and menopause: a narrative review. Maturitas. 2014;79:3–7. [PubMed]
Celec P, Mucska I, Ostantníková D, Hodosy J, authors. Testosterone and estradiol are not affected in male and female patients with obstructive sleep apnea treated with continuous positive airway pressure. J Endocrinol Invest. 2014;37:9–12. [PubMed]
Mermigkis C, Bouloukaki I, Mermigkis D, et al., authors. CRP evolution pattern in CPAP-treated obstructive sleep apnea patients. Does gender play a role? Sleep Breath. 2012;16:813–9. [PubMed]