The Effects of Transdermal Estradiol Alone or with Cyclical Dydrogesterone on Markers of Cardiovascular Disease Risk in Postmenopausal Women with Type 2 Diabetes: A Pilot Study

Abstract

The objective of this open, longitudinal, controlled study was to assess the effect of transdermal estradiol alone or combined with cyclical dydrogesterone on the markers of cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes. The control group consisted of postmenopausal diabetic women who declined menopausal hormone replacement therapy (HRT). Twenty-eight postmenopausal women (19 on HRT and 9 controls) with type 2 diabetes were followed up for 12 months. From the active treatment group 14 women with a uterus in situ had 80 microg/24 hr transdermal estradiol (Fematrix 80; Solvay Healthcare Ltd, Southampton, UK) and oral dydrogesterone 10 mg daily for the first 12 days of the calendar month, whereas 5 women with previous hysterectomy had 80 microg/24 hr transdermal estradiol (Fematrix 80) alone. CVD risk markers were measured before and at regular intervals after starting HRT. The main outcome measures were weight, systolic and diastolic blood pressure, fasting plasma glucose, glycated hemoglobin (HbA1c), glucose/insulin ratio, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein (a), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and endothelin-1. Transdermal estradiol with or without dydrogesterone in women with type 2 diabetes did not adversely affect any of the measured markers of cardiovascular risk. There was a significant decrease in HbA1c, total cholesterol, and LDL cholesterol at 6 months in women receiving HRT. Some of the cardiovascular disease risk markers may improve in postmenopausal women with type 2 diabetes with transdermal estradiol. This effect may have important clinical implications and it deserves further investigation in appropriately designed trials.

Effects of Hormone Replacement Therapy on Insulin Resistance and Platelet Function Tests

“…There was a significant decrease in HbA1c, total cholesterol and LDL cholesterol at 6 months in women receiving HRT. Other risk indicators such as HDL cholesterol, triglyceride, hsCRP, and fibrinogen were not changed as previously reported [19] . Likewise, a significant increase in fasting glucose was not seen in the women treated with combined conjugated equine estrogens and medroxyprogesterone acetate, suggesting a beneficial effect of HRT on fasting glucose [20] .…”

“…Stojanovic et al [19] suggested that transdermal estradiol with or without dydrogesterone in women with type 2 diabetes did not adversely affect any of the measured markers of cardiovascular risk in these women. There was a significant decrease in HbA1c, total cholesterol and LDL cholesterol at 6 months in women receiving HRT.…”

Estrogen and hypertension

“…Similarly, natural progesterone has not been found to interfere with the BP-lowering effect of transdermal estrogen [31]. Another prospective study also showed no difference in BP between the group of diabetic postmenopausal women randomized to transdermal estradiol plus dydrogesterone, a progestogen closely related to natural progesterone, and the group of women treated with transdermal estrogen alone [75]. More recently, drospirenone, a novel progestin with mineralocorticoid receptor antagonistic and antiandrogenic properties, has been shown to lower BP in hypertensive postmenopausal women when combined with oral estradiol [76].…”

High C‐reactive protein levels are associated with oral hormonal menopausal therapy but not with intrauterine levonorgestrel and transdermal estradiol

“…In fact, in women taking oral HRT, elevated CRP levels were repeatedly observed to occur during the first year of treatment, suggesting a key mechanism to excessive CVD morbidity [10,11]. However, transdermal HRT was not associated with an increase in CRP, apparently because of its avoidance of first-pass hepatic metabolism where CRP is synthesized under the estrogen effect [12][13][14][15][16]. Intrauterine levonorgestrel (LNG) combined with transdermal estrogen (TDE) is a relatively novel HRT combination whereby progestin is administered directly to the endometrium [17].…”