Also see:
High Estrogen and Heart Disease in Men
Oral Contraceptives, Estrogen, and Clotting
Quotes by Ray Peat, PhD
“Veins and capillaries are highly sensitive to estrogen, and women are more likely than men to have varicose veins, spider veins, leaky capillaries, and other vascular problems besides rosacea.”
“Spider veins are another anatomical variation that commonly appears under the influence of estrogen.”
“The pooling of blood in veins, a basic feature of shock, has recently become another of estrogen’s “protective” features for the circulatory system–the reasoning seems to be that reduced circulation of blood makes life easier for the circulatory system. The relevant contexts, though, are the contribution this makes to the formation of blood clots, and the quality of oxygenation of all tissues.”
“An excess of estrogen is associated with varicose veins in men, as well as women. (Raj, 2006; Ciarudullo, et al., 2000; Kendler, et al., 2009; Asciutto, et al., 2010; Raffeto, et al., 2010)”
J Vasc Surg. 2000 Sep;32(3):544-9.
High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women.
Ciardullo AV, Panico S, Bellati C, Rubba P, Rinaldi S, Iannuzzi A, Cioffi V, Iannuzzo G, Berrino F.
OBJECTIVE:
The purpose of this study was to determine if there is an association between elevated sex hormones (ie, serum estradiol, sex hormone binding globulin [SHBG], testosterone) and increased venous distension and clinical evidence of varicose veins in menopausal women.
METHODS:
Participants were 104 healthy volunteer menopausal women, aged 48 to 65 years, who were not undergoing hormonal treatment. Of these 104, 14 were excluded from analyses because their estradiol levels were compatible with a premenopausal condition (4), because they had missing values for insulin concentration (5), and because they did not show up at venous vessel examination (5). Patients underwent a physical examination to determine the presence of varicose veins; a venous strain-gauge plethysmographic examination to compute instrumental measures of venous distensibility; and laboratory analyses of blood so serum testosterone, estradiol, SHBG, glucose, and insulin could be measured. There were also prevalence ratios and odds ratios used to test the presence of an association between biochemical and instrumental variables.
RESULTS:
Serum levels of estradiol in the upper tertile of the frequency distribution were significantly associated with clinical evidence of varicose veins (prevalence odds ratios 3.6; 95% CI 1.1-11.6) and with increased lower limb venous distensibility (prevalence odds ratios 4.4; 95% CI 1.2-15.5). No association was found for SHBG and testosterone.
CONCLUSIONS:
Our finding that high serum levels of estradiol are associated with clinical evidence of varicose veins and instrumental measurements indicating increased venous distensibility in menopausal women suggests that endogenous estrogens may play a role in the development of this very common venous vessel abnormalities.
Angiology. 2009 Jun-Jul;60(3):283-9. doi: 10.1177/0003319708323493. Epub 2008 Oct 14.
Elevated serum estradiol/testosterone ratio in men with primary varicose veins compared with a healthy control group.
Kendler M, Blendinger Ch, Haas E.
The role of sex hormones in men with varicose veins remains unclear. Therefore, we set up a prospective pilot-study. In 34 men, venous blood was sampled during morning hours, for the determination of serum estradiol (E2), dehydroepiandrostendion, androstendion, and free testosterone (fT). Serum E2:fT ratio was calculated. The study protocol also included patient history, physical examination, color duplex ultrasound of both limbs, and assignment of CEAP clinical stage (C) classification. About 21 symptomatic varicose men (VM [C > or = 2] mean age of 40.3/+6.9 years) and 13 healthy men (HM [C < or = 1] mean age of 38.1/+ 7.4 years) were analyzed. The serum E2:fT ratio (VM 2.83/+ 0.79 and HM 2.32/+0.63) was significantly different (P < .05) between the two groups. No major differences were seen on the serum levels of the sex hormones. In summary, our results demonstrate a changed serum E2:fT ratio among men with varicose veins compared to healthy men. By the fact of a small study sample, the interpretabillity of this result is limited.
J Vasc Surg. 2010 Apr;51(4):972-81. doi: 10.1016/j.jvs.2009.11.074.
Estrogen receptor-mediated enhancement of venous relaxation in female rat: implications in sex-related differences in varicose veins.
Raffetto JD, Qiao X, Beauregard KG, Khalil RA.
BACKGROUND:
A greater incidence of varicose veins has been reported in premenopausal women than in men. We hypothesized that the sex differences in venous function reflect reduced constriction and enhanced venous dilation in women due to direct venous relaxation effects of estrogen on specific estrogen receptors (ER).
METHODS:
Circular segments of inferior vena cava (IVC) from male and female Sprague-Dawley rats were suspended between two wires, and isometric contraction (in mg/mg tissue) to phenylephrine, angiotensin II (AngII), and 96 mM KCl was measured. To investigate sex differences in venous smooth muscle, Ca(2+) release from the intracellular stores, and Ca(2+) entry from the extracellular space, the transient phenylephrine contraction in 0 Ca(2+) Krebs was measured. Extracellular CaCl(2) (0.1, 0.3, 0.6, 1, 2.5 mM) was added, and the [Ca(2+)](e)-dependent contraction was measured. To investigate sex differences in venous endothelial function, acetylcholine-induced relaxation was measured. To test the role of specific ERs, the amount of venous tissue ERs was measured using Western blots, and the venous relaxation in response to 17beta-estradiol (E2, activator of most ERs), 4,4,’4”-(4-propyl-[1H]-pyrazole-1,3,5-triyl)-tris-phenol (PPT; ERalpha agonist), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ERbeta agonist), and ICI 182,780 (ERalpha/ERbeta antagonist, and G protein-coupled receptor 30 [GPR30] agonist) was measured in IVC segments nontreated or treated with the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME).
RESULTS:
Phenylephrine caused concentration-dependent contraction that was less in female (max 104.2 +/- 16.2) than male IVC (172.4 +/- 20.4). AngII (10(-6))-induced contraction was also less in female (81.0 +/- 11.1) than male IVC (122.5 +/- 15.0). Phenylephrine contraction in 0 Ca(2+) Krebs was insignificantly less in female (4.8 +/- 1.8) than male IVC (7.2 +/- 1.7), suggesting little difference in the intracellular Ca(2+) release mechanism. In contrast, the [Ca(2+)](e)-dependent contraction was significantly reduced in female than male IVC. Also, contraction to membrane depolarization by 96 mM KCl, which stimulates Ca(2+) influx, was less in female (129.7 +/- 16.7) than male IVC (319.7 +/- 30.4), supporting sex differences in Ca(2+) entry. Acetylcholine relaxation was greater in female (max 80.6% +/- 4.1%) than male IVC (max 48.0% +/- 6.1%), suggesting sex differences in the endothelium-dependent relaxation pathway. Western blots revealed greater amounts of ERalpha, ERbeta, and GPR30 in female than male IVC. ER agonists caused concentration-dependent relaxation of phenylephrine contraction in female IVC. E2-induced relaxation (max 76.5% +/- 3.4%) was more than DPN (74.8% +/- 9.1%), PPT (71.4% +/- 12.5%), and ICI 182,780 (67.4% +/- 7.8%), and was similar in L-NAME-treated and nontreated IVC.
CONCLUSION:
The reduced alpha-adrenergic, AngII, depolarization-induced, and [Ca(2+)](e)-dependent venous contraction in female rats is consistent with sex differences in the Ca(2+) entry mechanisms, possibly due to enhanced endothelium-dependent vasodilation and increased ER expression/activity in female rats. E2/ER-mediated venous relaxation in female rats is not prevented by NOS blockade, suggesting activation of an NO-independent relaxation pathway. The decreased venous contraction and enhanced E2/ER-mediated venous relaxation would lead to more distensible veins in female rats.
Eur J Vasc Endovasc Surg. 2010 Jul;40(1):117-21. doi: 10.1016/j.ejvs.2010.01.023. Epub 2010 Mar 3.
Oestradiol levels in varicose vein blood of patients with and without pelvic vein incompetence (PVI): diagnostic implications.
Asciutto G, Mumme A, Asciutto KC, Geier B.
PURPOSE:
To assess the difference in the oestradiol levels of blood taken from varicose veins in patients with and without pelvic vein incompetence (PVI).
MATERIALS AND METHODS:
Women of child-bearing age with symptomatic primary or recurrent varicose veins of the great saphenous vein (GSV) were included in a prospective study. Patients underwent duplex ultrasonography and pelvic vein phlebography. They were divided into a group with PVI (PVI group) and a control group with GSV reflux alone (VV group). Blood samples were collected from the GSV at the sapheno-femoral junction or lower in the thigh as well as from the arm. Oestradiol levels were determined by electroluminescence.
RESULTS:
Between January and December 2007, 40 women were studied, of which 19 showed phlebographic evidence of PVI (PVI group), while 21 were included in the VV group. Phlebography revealed an incompetent ovarian vein in 14 (74%) patients of the PVI group, dilated uterine and ovarian plexuses in 12 (63%) and an incompetent internal iliac vein in six cases (32%). In the PVI group, the median oestradiol level in GSV samples was 121 pgml(-1) (range: 12-4300), while in the VV group the median level was 75 pgml(-1) (range: 9-1177). In the upper limb, the PVI group patients had a median level of 78 pgml(-1) (range: 15-121) and the VV group patients 68 pgml(-1) (range: 13-568). The ratio of lower limb/upper extremity was significantly higher (p<0.002) in patients of PVI group (median: 1.9; range: 0.7-33) than in those of the VV group (median: 1.1; range: 0.8-13). A threshold ratio of 1.4 showed the highest combined sensitivity and specificity in differentiating patients with PVI from those without.
CONCLUSIONS:
In patients with varicose veins arising from the GSV, oestradiol levels were significantly higher in the lower limb than in the upper extremity in the subgroup with associated PVI. It may be possible to use this observation as a diagnostic test in patients with suspected PVI. This deserves further study.
Indian Pacing Electrophysiol J. 2006 Apr-Jun; 6(2): 84–99.
The Postural Tachycardia Syndrome (POTS): Pathophysiology, Diagnosis & Management
Satish R Raj, MD MSCI
“The disorder primarily affects women of child-bearing age. The female:male ratio is 4:1. The reason for the strong female predominance is not known, but it should be noted that orthostatic tolerance is reduced in normal healthy females [7]. Others disorders such as autoimmune diseases and irritable bowel syndrome are seen commonly in patients with POTS, and also have higher prevalence in women.
Patients frequently report that their symptoms began following acute stressors such as pregnancy, major surgery, or a presumed viral illness, but in others cases, symptoms develop more insidiously. About 80% of female patients report an exacerbation of symptoms in the pre-menstrual phase of their ovulatory cycle (unpublished data). Gazit et al. have also reported an association between joint hypermobility and POTS [8]. Many patients have bowel irregularities and have been co-diagnosed with irritable bowel syndrome, and some have abnormalities of sudomotor regulation [9].”
