Effects of short-term transdermal hormone replacement therapy on glycaemic control, lipid metabolism, C-reactive protein and proteinuria in postmenopausal women with type 2 diabetes or hypertension

Abstract

Background: The study was carried out to evaluate the effects of short-term transdermal hormone replacement therapy (HRT) on glycaemic control, lipid metabolism, C-reactive protein (CRP) and proteinuria in high-risk post-menopausal women. Methods: A total of 20 well-controlled type 2 diabetic, hypertensive and 21 well-controlled glucose-tolerant, hypertensive postmenopausal women were prospectively enrolled. After 12 weeks of transdermal HRT, the changes in serum lipid sub-fractions, fasting glucose, fructosamine, glycated haemoglobin (HbA1c), CRP, creatinine, 24 h urine protein levels, creatinine clearance and blood pressure were evaluated. Results: After 12 weeks of treatment, serum total-cholesterol and low-density cholesterols (LDL-cholesterol) appeared slightly reduced and serum triglyceride slightly elevated, although non-significantly so in both groups. The increase in HDL-cholesterol (P < 0.05) and reduction in very low density (VLDL)-cholesterol (P < 0.05) levels were significant in hypertensive patients. Elevation in the Apolipoprotein A1 (P < 0.05) and reduction in the Apolipoprotein B (P < 0.05) levels were statistically significant in all patients. HRT was associated with significant decreases in serum fasting glucose (P < 0.05) and fructosamine (P < 0.05) levels in diabetic patients. Serum HbA1c, CRP, creatinine, 24 h urine protein levels, creatinine clearance and systolic and diastolic blood pressure did not change significantly in either group. Conclusions: There were no detrimental effects of transdermal HRT on lipid profile, glucose metabolism, CRP and urine protein levels in our well-controlled diabetic or hypertensive patients. A decision regarding HRT use should be taken on a case-by-case basis.

Results:All of the patients completed the study. The mean body mass index (BMI) was 31.27 and 30.95 kg/m2 in the DM-HRT and HT-HRT groups respectively. Estraderm TTS plus NETA was associated with statistically significant decreases in serum mean fasting glucose and fructosamine levels, and with a non-significant reduction in serum mean HbA1c level in the DM-HRT group. Significant changes were seen in mean serum VLDL (decreased) and HDL-cholesterol (increased) levels in the HT-HRT group. The increase in mean serum Apo-A1 level and the reduction in mean serum Apo-B level were statistically significant in both treatment groups. Serum CRP, creatinine, 24 h urine protein levels, creatinine clearance and systolic and diastolic blood pressure did not change significantly during 12 weeks of transdermal HRT in both groups. High-risk postmenopausal women did not have any adverse effect on proteinuria and serum creatinine levels after 3 months of Estraderm TTS plus NETA treatment.

TypeofStudy:A prospective, open study evaluating the effects of short-term hormone replacement therapy (HRT) Estraderm TTS plus norethisterone acetate (NETA) (=Estracombi TTS) on glycemic control, lipid metabolism, C-reactive protein (CRP) and proteinuria in high-risk postmenopausal women with diabetes and/or hypertension.

DosageDuration:17beta-estradiol 0.05 mg daily and sequential norethisterone acetate 0.25 mg daily transdermally. Duration was 12 weeks.

AdverseEffects:2 subjects (10%) in the DM-HRT group and 1 subject (4.7%) in the HT-HRT group complained about abnormal vaginal bleeding such as metrorrhagia and 4 patients (19%) reported breast tenderness in the HT-HRT group. No patient experienced detrimental effects on lipid profile, glucose metabolism, CRP and urine protein levels.

AuthorsConclusions:Additional research will be necessary to determine the effects of long-term transdermal HRT in high-risk postmenopausal women. We conclude that decisions about HRT should be taken on a case-by-case basis, and in doing so it is important to include the potential personal benefits and risk profile, especially in high-risk postmenopausal women.

FreeText:In order to maintain their glucose levels in an acceptable range, women with type 2 diabetes were on dietary management alone (2 patients) or taking oral antidiabetic drugs that consisted of metformin and sulfonylureas (18 patients). Each diabetic patient received a diabetic diet with <30% of total calories as fat, ?10% saturated fat, ?10% monounsaturated fat and ?10% polyunsaturated fat. All patients took amlodipine 5-10 mg daily as an antihypertensive drug. The antidiabetic and antihypertensive medications were left unchanged during the study. Metabolic and physical examinations were performed at the onset of the study and then again after 12 weeks of receiving HRT. Blood pressure was measured during two clinical evaluations by an average of three measurements taken in the sitting position before the morning dose of the antihypertensive therapy. On the fourth day of the third hormonal cycle (in the estrogen only phase), blood samples were taken after a 10 h fast and serum total cholesterol (total cholesterol), triglyceride (TG), high density cholesterol (HDL-cholesterol), VLDL-cholesterol, apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), serum creatinine (sCr), urine creatinine (uCr), 24 h urine protein, fructosamine, HbA1c and glucose levels were determined in an automated analyzer. Low-density cholesterol (LDL cholesterol) levels were calculated by using Friedewald's formula. Serum CRP was turbidimetrically determined by clinical chemistry system.

Indications:20 patients with diabetes type 2 and hypertension and 21 patients with hypertension.

Patients:41 postmenopausal women. Type 2 diabetes and hypertension group (DM-HRT group): n=20, mean age was 50.9 years. Hypertension group (HT-HRT group): n=21, mean age was 52.6 years.