The impact of hormonal contraceptives containing estradiol, estradiol valerate, and estetrol on liver proteins, lipids, glucose, blood pressure, and bone. A literature review.

OBJECTIVE

We investigated the metabolic profile induced by contraceptives containing body-identical oestrogens.

METHODS

A literature search was made for articles on contraceptives with oestradiol/nomegestrol acetate (E2/NOMAc), oestradiol valerate/dienogest (E2V/DNG), estetrol/drospirenone (E4/DRSP) and metabolic parameters.

RESULTS

The three formulations induced a similar, slight but significant increase of liver proteins. Levels of angiotensinogen were measured only during E4/DRSP, and were significantly increased (p < 0.05). Scanty data indicate a neutral effect of the three formulations on blood pressure. Lipids and lipoproteins were not modified by E2/NOMAc and E2V/DNG, while triglycerides slightly but significantly increased (p < 0.05) during E4/DRSP. Fasting glucose was unaffected by any association while fasting insulin increased during E2/NOMAc and E2V/DNG. Data were not reported for E4/DRSP. Insulin resistance was increased by E4/DRSP and not by E2V/DNG. Bone turnover was tested only in users of E2V/DNG. Markers of bone formation did not change while markers of bone absorption decreased. Bone mineral density (BMD) did not change after 6 months of E2V/DNG and after 2 years of E2/NOMAc. No data on BMD is available for users of E4/DRSP.

CONCLUSIONS

The three contraceptive formulations exert a similar, almost neutral effect on metabolism and blood pressure. Only a slight increase of triglycerides and a decrease of insulin sensitivity emerged with the use of E4/DRSP. The few data on bone, suggest a neutral effect of E2V/DNG and E2/NOMAc. There is no data evaluating the effect of the contraceptive association of E4/DRSP on bone.