The allopregnanolone to progesterone ratio across the menstrual cycle and in menopause

PSYCHONEUROENDOCRINOLOGY

卷:112

Article

Kimball, Allison¹  Dichtel, Laura E.¹  Nyer, Maren B.²  Mischoulon, David²  Fisher, Lauren B.²  Cusin, Cristina²  Dording, Christina M.²  Nhi-Ha Trinh²  Yeung, Albert²  Haines, Melanie S.¹  Sung, Joshua C.³  Pinna, Graziano⁴  Rasmusson, Ann M.^5,6  Carpenter, Linda L.⁷  Fava, Maurizio⁸  Klibanski, Anne¹  Miller, Karen Klahr¹ 

[1] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA

[4] Univ Illinois, Dept Psychiat, Inst Psychiat, Chicago, IL 60612 USA

[5] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Dept Vet Affairs, Boston, MA 02118 USA

[6] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA

[7] Butler Hosp, Brown Dept Psychiat & Human Behav, Providence, RI 02906 USA

[8] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA

关键词: Neuroactive steroids;    Allopregnanolone;    Menstrual cycle;    Menopause;   

DOI  :  10.1016/j.psyneuen.2019.104512

来源: Elsevier

【 摘 要 】

The neuroactive steroid 3 alpha-5 alpha-tetrahydroprogesterone (allopregnanolone), a metabolite of progesterone, is a positive allosteric modulator of GABA A receptors, and low levels have been implicated in the etiology of mood disorders. However, it is not known whether metabolism of progesterone to allopregnanolone varies across the menstrual cycle or is low after menopause. We hypothesized that the allopregnanolone/progesterone ratio would decrease from the follicular to luteal phase. We also hypothesized that postmenopausal women would have lower levels of progesterone and allopregnanolone but similar allopregnanolone/progesterone ratios as premenopausal women in the follicular phase. Serum fasting allopregnanolone and progesterone levels were measured by gas chromatography-mass spectrometry in ten premenopausal women at the follicular, mid-cycle, and luteal phases of the menstrual cycle and in twenty-four postmenopausal women. Although allopregnanolone and progesterone levels increased from the follicular to luteal phase, the allopregnanolone/progesterone ratio decreased 8-fold [0.33 +/- 0.08 (follicular) vs 0.16 +/- 0.09 (mid-cycle) vs 0.04 +/- 0.007 (luteal), p = 0.0003]. Mean allopregnanolone and progesterone levels were lower in postmenopausal than premenopausal women at all menstrual cycle phases (p < 0.01). The mean allopregnanolone/progesterone ratio was similar in postmenopausal and premenopausal women in the follicular phase (0.39 +/- 0.08 vs 0.33 +/- 0.08, p = 0.94) but was significantly lower at mid-cycle and in the luteal phase than in postmenopausal women (p < 0.01). In conclusion, the serum allopregnanolone/progesterone ratio decreases 8-fold from the follicular to luteal phase and is lower at mid-cycle and the luteal phase than in postmenopausal women. Whether these data have implications for luteal phase and other mood disorders merits further study.

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