Abstract
Many studies of vascular function limit the testing of premenopausal female participants to periods when female sex hormones, either endogenous or exogenous, are at their lowest concentration. This practice, when not part of the specific research question, may limit data surrounding the predominant physiological state of premenopausal females and pose a threat to external validity. In this Perspective, we briefly review the literature on the effect of female sex hormones on vascular function and discuss when limiting experimental testing to a certain phase of the menstrual cycle (MC) or oral contraceptive (OC) use may be appropriate. The goal of this Perspective is to open a dialog that may enhance data validity and the overall understanding of vascular function in premenopausal females.
Highlights
In vascular outcome research, current practice of many investigators is to limit experimental testing of premenopausal female participants to periods of low hormone concentration, such as the early follicular (EF) phase (~days 1–5) of the menstrual cycle (MC) or placebo phase of oral contraceptive (OC) use
It currently remains unclear whether ERβ action or reduced inflammation in response to I-R contribute to the preserved flow mediated dilation (FMD) response during the late follicular (LF) phase in premenopausal females
There is limited data regarding the impact of intrauterine devices (IUD) on markers of vascular or endothelial function, but studies that have been conducted suggest no changes in IUD users compared to non-users (Selim and Hussein, 2013; Zueff et al, 2017)
Summary
Current practice of many investigators is to limit experimental testing of premenopausal female participants to periods of low hormone concentration, such as the early follicular (EF) phase (~days 1–5) of the menstrual cycle (MC) or placebo phase of oral contraceptive (OC) use. Because of the role of estrogen and other female sex hormones in vascular control mechanisms, and the dynamic range of circulating female sex hormones across the normal MC, limiting experimental testing of premenopausal females to low hormone states represents a threat to external validity This traditional concept of controlling for female sex hormones by minimizing their effect may be more appropriately replaced by other control practices, such as accounting for MC/OC phase, assessing circulating hormone concentrations or systematically testing during more than one hormone phase. Rat studies suggest the protection from I-R injury in females compared to males may be related to the action of a subtype of estrogen receptor (ER), ERβ (Gabel et al, 2005), or a diminished inflammatory response (Wang et al, 2005) It currently remains unclear whether ERβ action or reduced inflammation in response to I-R contribute to the preserved FMD response during the LF phase in premenopausal females. It is unclear whether these mechanisms are modified across different MC or OC phases
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