Blood pressure and water regulation: understanding sex hormone effects within and between men and women

Abstract

Cardiovascular disease remains the leading cause of death for both men and women. Hypertension is less prevalent in young women compared with young men, but menopausal women are at greater risk for hypertension compared with men of similar age. Despite these risks, women do not consistently receive first line treatment for the early stages of hypertension, and the greater morbidity in menopause reflects this neglect. This review focuses on ovarian hormone effects on the cardiovascular and water regulatory systems that are associated with blood pressure control in women. The study of ovarian hormones within young women is complex because these hormones fluctuate across the menstrual cycle, and these fluctuations can complicate conclusions regarding sex differences. To better isolate the effects of oestrogen and progesterone on the cardiovascular and water regulation systems, we developed a model to transiently suppress reproductive function followed by controlled hormone administration. Sex differences in autonomic regulation of blood pressure appear related to ovarian hormone exposure, and these hormonal differences contribute to sex differences in hypertension and orthostatic tolerance. Oestrogen and progesterone exposure are also associated with plasma volume expansion, and a leftward shift in the osmotic operating point for body fluid regulation. In young, healthy women, the shift in osmoregulation appears to have only a minor effect on overall body water balance. Our overarching conclusion is that ovarian hormone exposure is the important underlying factor contributing to differences in blood pressure and water regulation between women and men, and within women throughout the lifespan.

Figures

Figure 1. Plasma fluctuations of hormones and gonadotropins over a normal 28 day menstrual cycle

A, follicle stimulating hormone (FSH) and luteinizing hormone (LH); B, oestrogens and progesterone. C, changes in 17 β-oestradiol and progesterone during gonadotropin releasing hormone (GnRH) antagonist administration followed by 17 β-oestradiol and progesterone administration.

Figure 2. Muscle sympathetic nerve activity (MSNA) burst frequency (A) and total activity (B) responses during a graded upright tilt in men and women during the early follicular phase (oestrogen and progesterone are low) and the mid-luteal phase (oestrogen and progesterone are high)

Data are mean ± SEM. Tilt5, Tilt10, Tilt20, Tilt30, Tilt40 and Tilt45 are 5, 10, 20, 30, 40 and 45 min after 60 deg upright tilt. From Fu et al. (2009) with permission.

Figure 3. Mean plasma arginine vasopressin concentration (P[AVP]) in response to increases in POsm during hypertonic saline infusion in the early follicular and mid-luteal phases in women and in men

Data are mean ± SEM. From Stachenfeld et al. (2001).

Figure 4. Mean P[AVP] and mean thirst responses to increases in plasma osmolality (POsm) during hypertonic saline infusion in the early follicular and mid-luteal phases and during oral contraceptive treatment with progesterone only and combined oestrogen and progesterone

Data are mean ± SEM. From Calzone et al. (2001).

Figure 5. Mean plasma arginine vasopressin concentration (P[AVP]) responses to increases in plasma osmolality (POsm) during hypertonic saline infusion (over 105 min) during lupron administration (GnRH antagonist) alone and with 17 β-oestradiol administration

Data are mean ± SEM.*P < 0.05, GnRHa alone versus hormone treatment. From Stachenfeld & Keefe (2002).

Figure 6. Mean urine osmolality as a function of mean plasma arginine vasopressins concentration (P[AVP]) in response to synthetic AVP infusions duirng administration of a gonadotropin releasing agonist (luprolide, GnRH antagonist) alone and with 17 β-oestradiol

Data are mean ± SEM. (Adapted from Stachenfeld et al. (2003).