Effects of estrogen and progesterone on cerebrovascular responses to euoxic hypercapnia in women

ABSTRACT

Objectives To determine the cerebral blood flow response to step changes in end-tidal Pco₂ in premenopausal women (n = 10; mean age±standard deviation 27.0±6.4 years) during the follicular (FP), mid-cycle (MC) and luteal (LP) phases of the menstrual cycle.

Methods Transcranial Doppler ultrasound was used to measure beat-by-beat averaged peak blood flow velocity () in the middle cerebral artery in response to 20 min of euoxic hypercapnia (end-tidal Po₂ = 88 Torr; end-tidal Pco₂ = 7.0 Torr above resting values). The responses to euoxic hypercapnia were fitted to a simple mathematical model that included gain terms for the on (G_on) and off (G_off) responses, time constants for the on (τ_on) and off (τ_off) responses, baseline terms and a time delay (T_d).

Results Serum progesterone levels were significantly greater for LP compared to FP and MC (40.6±13.2 vs. 32.6±1.4 nmol/l (p < 0.001) and 8.8±3.8 nmol/l (p < 0.001), respectively). Serum estrogen concentrations were significantly lower in FP compared to MC and LP (150.9±51.2 vs. 506.5±220.5 pmol/l (p = 0.002) and 589.1±222.8 pmol/l (p < 0.001), respectively). Arterial Pco₂ was significantly greater in MC compared to LP (35.0±2.1 and 32.6±1.4 Torr, respectively; p = 0.02). There was a significant increase in G_off during LP compared with FP and MC (3.38±0.68 vs. 2.79±0.82 cm s⁻¹ Torr⁻¹ (p = 0.021) and 2.74±0.90 (p = 0.018) cm s⁻¹ Torr2¹, respectively). Progesterone and the estrogen/progesterone ratio contributed to the observed differences in G_off.

Conclusion There is an increase in G_off during LP that is explained, at least in part, by increases in serum progesterone and estrogen and a decrease in arterial Pco₂.

Key words::

• CEREBRAL BLOOD FLOW
• ESTROGEN
• MIDDLE CEREBRAL ARTERY
• TRANSCRANIAL DOPPLER ULTRASOUND
• MENSTRUAL CYCLE
• PROGESTERONE

ACKNOWLEDGEMENTS

The authors would like to thank their dedicated subjects for their participation in this study.

Conflict of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Source of funding This study was supported by the Alberta Heritage Foundation for Medical Research (AHFMR), the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Foundation for Innovation. C.T.D. was supported by a National Science and Engineering Research Council Graduate Scholarship, K. I. was supported by an AHFMR Postdoctoral Fellowship, and M. J. P. was supported by a CIHR New Investigator Award and an AHFMR Senior Medical Scholarship.