Associations of Sex Hormones and Hormonal Status With Arterial Stiffness in a Female Sample From Reproductive Years to Menopause

Abstract

ObjectiveLoss of sex hormones has been suggested to underlie menopause-associated increment in cardiovascular risk. We investigated associations of sex hormones with arterial stiffness in 19–58-years-old women. We also studied associations of specific hormonal stages, including natural menstrual cycle, cycle with combined oral contraceptives (COC) and menopausal status with or without hormone therapy (HT), with arterial stiffness.MethodsThis study includes repeated measurements of 65 healthy women representing reproductive (n=16 natural, n=10 COC-users) and menopause (n=5 perimenopausal, n=26 postmenopausal, n=8 HT-users) stages. Arterial stiffness outcomes were aortic pulse wave velocity (PWVao) and augmentation index (AIx%) assessed using Arteriograph-device. Generalized estimating equation models were constructed to investigate associations of each hormone (wide age-range models) or hormonal stage (age-group focused models) with arterial stiffness. PWVao models with cross-sectional approach, were adjusted for age, relative fitness, fat mass and mean arterial pressure, while models with longitudinal approach were adjusted for mean arterial pressure. AIx% models used the same approach for adjustments and were also adjusted for heart rate.ResultsNegative and positive associations with arterial stiffness variables were observed for estradiol and follicle-stimulating hormone, respectively, until adjustment for confounding effect of age. In naturally menstruating women, AIx% was higher at ovulation (B=3.63, p<0.001) compared to the early follicular phase. In COC-users, PWVao was lower during active (B=-0.33 - -0.57, p<0.05) than inactive pills. In menopausal women, HT-users had higher PWVao (B=1.43, p=0.03) than postmenopausal non-HT-users.ConclusionsWhen using wide age-range assessments covering reproductive to menopausal lifespan it is difficult to differentiate age- and hormone-mediated associations, because age-mediated influence on arterial stiffness seemed to overrule potential hormone-mediated influences. However, hormonal status associated differentially with arterial stiffness in age-group focused analyses. Thus, the role of sex hormones cannot be excluded. Further research is warranted to resolve potential hormone-mediated mechanisms affecting arterial elasticity.

Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers

“…To investigate the RNA content of EV and HDL particles, we collected plasma samples after overnight fasting from a subset of “Estrogen, microRNAs and the risk of metabolic dysfunction (EsmiRs) study” (Laakkonen et al, 2021) participants, consisting of 18 postmenopausal women (age range 52–57 years, Table S1). Of these women, nine used estrogen-based hormonal therapy (HT), and nine were HT nonusers.…”

The Association Between Route of Post-menopausal Estrogen Administration and Blood Pressure and Arterial Stiffness in Community-Dwelling Women

“…Interestingly, arterial compliance increased significantly in hormone users after 4 weeks of cessation, but the authors did not report the route of estrogen administration or concomitant progestin use (18). Conversely, a recent crosssectional study (19) of 36 menopausal women reported that hormone therapy (six oral, two transdermal estrogen)-users had higher aPWV, consistent with greater cardiovascular risk, than postmenopausal non-users (n = 26), although the authors did not report whether hormone therapy included a progestin. Similar to studies examining the effect of postmenopausal hormone therapy on blood pressure, it is possible that factors other than the route of estrogen administration contributed to the reported outcomes, including differing methodologies to measure arterial stiffness (54).…”

“…Previous studies have examined the impact of different routes of estrogen administration on vascular measures and have shown conflicting results (6,8,(14)(15)(16)(17)(18)(19), which is most likely due to differences in study populations, age and cause of menopause, timing of postmenopausal hormone initiation, and notably, the presence of progestin. The Women's Health Initiative (WHI), a trial in which postmenopausal women with a uterus were randomized to both oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) or placebo was stopped early due to negative cardiovascular outcomes in the intervention arm (3).…”

Significance of Low Muscle Mass on Arterial Stiffness as Measured by Cardio-Ankle Vascular Index

“…Sex hormones and their association with arterial stiffness is rather complex, especially in the women population with variable menstrual status. Laakkonen et al reported that age- and hormone-mediated associations in arterial stiffness cannot be differentiated, but still suggested that the potential role of sex hormones as hormonal status was differentially associated with arterial stiffness in age-group focused analyses ( 38 ). Overall, there may be a hormonal influence, albeit its power as a cardiovascular risk factor over other traditional risk factors may not be very strong.…”