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A case of resolution of amenorrhea after CPAP therapy for obstructive sleep apnea
Sleep Medicine 11 (2010) 224–226
Contents lists available at ScienceDirect
Sleep Medicine journal homepage: www.elsevier.com/locate/sleep
Letters to the Editor A case of resolution of amenorrhea after CPAP therapy for obstructive sleep apnea Dear Editor: We present a case of a 47-year-old Caucasian woman who reported symptoms of snoring, excessive daytime sleepiness, and witnessed apneas. She also had frequent nocturnal diaphoresis, which she attributed to the onset of possible menopause. The patient underwent a split night polysomnogram with continuous positive airway pressure (CPAP) titration, which demonstrated obstructive sleep apnea (OSA). At a CPAP titration pressure of 6 cm H2O, the respiratory disturbance index (RDI) was reduced to 6.0 and minimum oxyhemoglobin saturation rose to 87%. The patient had laboratory work-up for her menopausal symptoms shortly after the sleep study. The human chorionic gonadotropin (HCG) level was 2.1 mI U/ml. Follicle stimulating hormone (FSH) level was 52 mI U/ml. Lutenizing hormone (LH) level was 35.3 mI U/ml. Prolactin level was 6.5 N G/ml. These levels were consistent with a post-menopausal state. Upon the patient’s return to the sleep clinic 3 months after CPAP use, an improvement in her symptoms was noted. Also, the patient started having her menstrual cycles again at regular 28day periods, which had stopped 8 months prior. A repeat series of laboratory work was initiated. The FSH level was now 3.2 mI U/ml. The LH level was 8.1 mI U/ml. The prolactin level was 49.9 N G/ml. Approximately five weeks later a repeat FSH level was taken and was noted to be 2.1 mI U/ml. A HCG level was noted to be <2 mI U/ ml. LH was 3.2 mI U/ml. These results were no longer in the range of menopausal patients and indicated the return of normal cycling of these hormones as seen with normal menstrual cycles. The pulsatile release of luteinizing hormone is responsible for ovulation. Without ovulation, no endometrial proliferation would occur and thus no menses. Orexin-A is also found to modulate the pulsatile release of LH in animal studies [1–3]. Although one study [4] showed the contrary, other studies showed that individuals with OSA have chronically low levels of Orexin-A [5–7]. This decrease in Orexin-A could be what eliminates the pulsatility of LH release in humans. Orexin-A returns to normal levels with correction of the OSA with CPAP therapy [8]. Since Orexin-A production returns with correction of OSA, it could then allow for pulsatile release of LH and thus initiate resumption of ovulation and subsequent menses. We did not estimate orexin-A levels in our patient. This is speculation, but unfortunately further work into OSA’s effect on the menstrual cycle and its hormonal regulation is required. Acknowledgements Dr. Rifkin is a clinical researcher and has received research support from the pharmaceutical and medical equipment industry. Specifically, in regard to this letter to the editor, Dr. Rifkin has
received support (in excess of USD $10,000) to perform research on a medical device unrelated to this letter for ResMed. ResMed, among other activities, is a manufacturer of CPAP equipment. Furthermore, Dr. Rifkin is also an employee and stock holder (in excess of USD $10,000) of Avastra, USA, a sleep diagnostics company and durable medical equipment supplier. The remaining authors have nothing to disclose. No financial support or off-label or investigational use trials were performed by any of the authors of this manuscript. References [1] Small CJ, Goubillon ML, Murray JF, Siddiqui A, Grimshaw SE, Young H, Sivanesan V, et al. Central Orexin-A has site-specific effects on luteinizing hormone release in female rats. Endocrinology 2003;144:3225–36. [2] Furuta M, Funabashi T, Kimura F. Suppressive action of Orexin-A on pulsatile luteinizing hormone secretion is potentiated by a low dose of estrogen in ovariectomized rats. Neuroendocrinology 2002;75:151–7. [3] Kohsaka A, Watanobe H, Kakizaki Y, Suda T, Schiöth HB. A significant participation of Orexin-A, a potent orexigenic peptide, in the preovulatory luteinizing hormone and prolactin surges in the rat. Brain Res 2001;898:166–70. [4] Igarashi N, Tatsumi K, Nakamura A, et al. Plasma Orexin-A levels in obstructive sleep apnea hypopnea syndrome. Chest 2003;124:1381–5. [5] Nishijima T, Sakurai S, Arihara Z, Takahashi K. Plasma Orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome. Peptides 2003;24:407–11. [6] Sakurai S, Nishijima T, Takahashi JS, Yamauchi K, Arihara Z, Takahashi K. Clinical significance of daytime plasma Orexin-A-like immunoreactivity concentrations in patients with obstructive sleep apnea-hypopnea syndrome. Respiration 2004;71:380–4. [7] Busquets X, Barbé F, Barceló A, et al. Decreased plasma levels of Orexin-A in sleep apnea. Respiration 2004;71:575–9. [8] Sakurai S, Nishijima T, Takahashi S, Yamauchi K, Arihara Z, Takahashi K. Low plasma Orexin-A levels were improved by continuous positive airway pressure treatment in patients with severe obstructive sleep apnea-hypopnea syndrome. Chest 2005;127:731–7.
Bijal Kirit Mehta * Dept. of Neurology, SUNY Buffalo, 100 High Street, Buffalo, NY 14203, USA * Tel.: +1 949 547 6875. E-mail address: [email protected] Nicolas Saikali Dept. of Neurology, SUNY Buffalo, 100 High Street, Buffalo, NY 14203, USA Marc Schlegel Sleep Centers of Western New York, Buffalo, NY 14203, USA Daniel Rifkin Dept. of Neurology, SUNY Buffalo, Buffalo, NY 14203, USA Sleep Centers of Western New York, Buffalo, NY 14203, USA 1389-9457/$ - see front matter Ó 2009 Published by Elsevier B.V. doi:10.1016/j.sleep.2009.06.002
Contents lists available at ScienceDirect
Sleep Medicine journal homepage: www.elsevier.com/locate/sleep
Letters to the Editor A case of resolution of amenorrhea after CPAP therapy for obstructive sleep apnea Dear Editor: We present a case of a 47-year-old Caucasian woman who reported symptoms of snoring, excessive daytime sleepiness, and witnessed apneas. She also had frequent nocturnal diaphoresis, which she attributed to the onset of possible menopause. The patient underwent a split night polysomnogram with continuous positive airway pressure (CPAP) titration, which demonstrated obstructive sleep apnea (OSA). At a CPAP titration pressure of 6 cm H2O, the respiratory disturbance index (RDI) was reduced to 6.0 and minimum oxyhemoglobin saturation rose to 87%. The patient had laboratory work-up for her menopausal symptoms shortly after the sleep study. The human chorionic gonadotropin (HCG) level was 2.1 mI U/ml. Follicle stimulating hormone (FSH) level was 52 mI U/ml. Lutenizing hormone (LH) level was 35.3 mI U/ml. Prolactin level was 6.5 N G/ml. These levels were consistent with a post-menopausal state. Upon the patient’s return to the sleep clinic 3 months after CPAP use, an improvement in her symptoms was noted. Also, the patient started having her menstrual cycles again at regular 28day periods, which had stopped 8 months prior. A repeat series of laboratory work was initiated. The FSH level was now 3.2 mI U/ml. The LH level was 8.1 mI U/ml. The prolactin level was 49.9 N G/ml. Approximately five weeks later a repeat FSH level was taken and was noted to be 2.1 mI U/ml. A HCG level was noted to be <2 mI U/ ml. LH was 3.2 mI U/ml. These results were no longer in the range of menopausal patients and indicated the return of normal cycling of these hormones as seen with normal menstrual cycles. The pulsatile release of luteinizing hormone is responsible for ovulation. Without ovulation, no endometrial proliferation would occur and thus no menses. Orexin-A is also found to modulate the pulsatile release of LH in animal studies [1–3]. Although one study [4] showed the contrary, other studies showed that individuals with OSA have chronically low levels of Orexin-A [5–7]. This decrease in Orexin-A could be what eliminates the pulsatility of LH release in humans. Orexin-A returns to normal levels with correction of the OSA with CPAP therapy [8]. Since Orexin-A production returns with correction of OSA, it could then allow for pulsatile release of LH and thus initiate resumption of ovulation and subsequent menses. We did not estimate orexin-A levels in our patient. This is speculation, but unfortunately further work into OSA’s effect on the menstrual cycle and its hormonal regulation is required. Acknowledgements Dr. Rifkin is a clinical researcher and has received research support from the pharmaceutical and medical equipment industry. Specifically, in regard to this letter to the editor, Dr. Rifkin has
received support (in excess of USD $10,000) to perform research on a medical device unrelated to this letter for ResMed. ResMed, among other activities, is a manufacturer of CPAP equipment. Furthermore, Dr. Rifkin is also an employee and stock holder (in excess of USD $10,000) of Avastra, USA, a sleep diagnostics company and durable medical equipment supplier. The remaining authors have nothing to disclose. No financial support or off-label or investigational use trials were performed by any of the authors of this manuscript. References [1] Small CJ, Goubillon ML, Murray JF, Siddiqui A, Grimshaw SE, Young H, Sivanesan V, et al. Central Orexin-A has site-specific effects on luteinizing hormone release in female rats. Endocrinology 2003;144:3225–36. [2] Furuta M, Funabashi T, Kimura F. Suppressive action of Orexin-A on pulsatile luteinizing hormone secretion is potentiated by a low dose of estrogen in ovariectomized rats. Neuroendocrinology 2002;75:151–7. [3] Kohsaka A, Watanobe H, Kakizaki Y, Suda T, Schiöth HB. A significant participation of Orexin-A, a potent orexigenic peptide, in the preovulatory luteinizing hormone and prolactin surges in the rat. Brain Res 2001;898:166–70. [4] Igarashi N, Tatsumi K, Nakamura A, et al. Plasma Orexin-A levels in obstructive sleep apnea hypopnea syndrome. Chest 2003;124:1381–5. [5] Nishijima T, Sakurai S, Arihara Z, Takahashi K. Plasma Orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome. Peptides 2003;24:407–11. [6] Sakurai S, Nishijima T, Takahashi JS, Yamauchi K, Arihara Z, Takahashi K. Clinical significance of daytime plasma Orexin-A-like immunoreactivity concentrations in patients with obstructive sleep apnea-hypopnea syndrome. Respiration 2004;71:380–4. [7] Busquets X, Barbé F, Barceló A, et al. Decreased plasma levels of Orexin-A in sleep apnea. Respiration 2004;71:575–9. [8] Sakurai S, Nishijima T, Takahashi S, Yamauchi K, Arihara Z, Takahashi K. Low plasma Orexin-A levels were improved by continuous positive airway pressure treatment in patients with severe obstructive sleep apnea-hypopnea syndrome. Chest 2005;127:731–7.
Bijal Kirit Mehta * Dept. of Neurology, SUNY Buffalo, 100 High Street, Buffalo, NY 14203, USA * Tel.: +1 949 547 6875. E-mail address: [email protected] Nicolas Saikali Dept. of Neurology, SUNY Buffalo, 100 High Street, Buffalo, NY 14203, USA Marc Schlegel Sleep Centers of Western New York, Buffalo, NY 14203, USA Daniel Rifkin Dept. of Neurology, SUNY Buffalo, Buffalo, NY 14203, USA Sleep Centers of Western New York, Buffalo, NY 14203, USA 1389-9457/$ - see front matter Ó 2009 Published by Elsevier B.V. doi:10.1016/j.sleep.2009.06.002