Assessment of liver function tests of women taking hormonal contraceptives at University of Gondar comprehensive specialized hospital and Family Guidance Association of Gondar (FGAE), 2022; a comparative cross-sectional study
Authors: Chane Elias , Wondifraw Habtamu , Hadgu Rishan , Fasil Alebachew 
Published: August 2023

Introduction
Hormonal contraceptives are artificial preparations that contain artificial progestins and Ethinylestradiol; these preparations are utilized by women of reproductive age to prevent pregnancy. Roughly a billion women in the world use some form of contraceptive worldwide. Despite the utility of these preparations, they are linked with several adverse effects, including disturbances of liver functionality and integrity. However, previous studies conducted to assess the association between hormonal contraceptive utilization and liver function tests reported conflicting results, and the effects remained a matter of concern.

Methods
The study enrolled a total of 264 participants, who were allocated into two groups. One group of hormonal contraceptive users who use the medication for a minimum of six months: Depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), Norplant, and Implant users and another age-matched non-user control group in a ratio of 1:1. A semi-structured questionnaire was used to collect socio-demographic, behavioral, and clinical data. Five ml serum blood sample was collected for liver function test analysis on a Beckman Coulter Clinical Chemistry analyzer (DXC 700 AU). Independent t-test was used to compare liver function tests of hormonal contraceptive users and non-user controls, whereas ANOVA followed by a Bonferroni post hoc test was used for intra- (between classes of contraceptives) and inter-group (between each class of contraceptives and controls) comparisons and to identify factors associated.

Results
Hormonal contraceptive users were observed to have a statistically significant higher mean value of liver enzymes assessed compared to non-user control groups: aspartate aminotransferase (AST) (47.07±14.79 versus 25.92±7.37; p <0.001), alanine aminotransferase (ALT) (35.83±13.76 versus 16.56 ± 5.03; p <0.001), alkaline phosphatase (ALP) (63.34±14.74 versus 45.41±14.34, p <0.001) and for γ-glutamyl transferase (GGT) (47.37±24.32 versus 19.45 ± 6.86 p <0.001). Similarly, the mean value of total and direct bilirubin (mg/dL) among HC users showed a statistically significant elevation (0.68 ± 0.22 against 0.32 ± 0.13, p <0.001) for total bilirubin and (0.14 ± 0.06 against 0.06 ± 0.03, p <0.001) for direct bilirubin respectively. However, no statistically significant result was observed in the mean values of total protein and albumin. For total protein (6.7 ± 0.89 versus 6.5 ± 1.15, p 0.07) and for albumin (5.4 ± 0.92 versus 5.3 ± 1.08; p 0.30). The current study also indicates the level of hepatic function test alteration is related to the type of hormonal contraceptives, duration of usage, and level of adherence to a specific class of contraceptives.

Conclusion and recommendation
Hormonal contraceptive use was observed to affect hepatic function. Based on this finding, we strongly recommend to closely monitor liver function tests in women using hormonal contraceptives.