Influence of progestin-only hormonal use on hepatocellular adenomas: A retrospective cohort study

Abstract

Objectives: Exogenous estrogen is associated with growth of hepatocellular adenomas (HCAs), although the influence of progestin-only agents is unknown. We therefore evaluated the association of progestin-only agents on HCA progression compared to no hormone exposure and compared to estrogen exposure in female patients.

Study design: In this single-center, retrospective cohort study of reproductive-aged female patients (ages 16-45) with diagnosed HCAs between 2003 and 2021, we evaluated radiographic HCA growth during discrete periods of well-defined exogenous hormone exposures.

Results: A total of 34 patients were included. Nineteen (55.9%) had follow-up scans during periods without hormone exposure, 7 (20.6%) during estrogen exposure, and 8 (23.5%) during progestin-only exposure. Over a median follow-up of 11 months, percent change in sum of adenoma diameters from baseline to last available scan was -15.0% with progestin-only agents versus 29.4% with estrogen exposure (p = 0.04), and -7.4% with no hormonal exposure (p = 0.52 compared to progestin-only). Greater than 10% growth was observed in two individuals (25.0%) with progestin-only agent use (one patient on high-dose progestin for menorrhagia) versus five individuals (71.4%) with estrogen use (p = 0.13), and 7 (36.8%) with no exogenous hormone use (p = 0.68 vs progestin-only).

Conclusions: During discrete periods of progestin-only use, HCA growth overall declined, similar to declining growth during periods without exogenous hormonal exposure. This differed from discrete periods of exogenous estrogen exposure, during which time HCAs demonstrated overall increased growth. Though larger studies are needed, these findings support recent guidance supporting progestin-only agents for female patients with HCAs seeking non-estrogen alternatives for contraception.

Implications: In this small retrospective study, we observed overall decrease in HCA size during discrete periods of progestin-only contraception use, similar to that observed during periods without exogenous hormone exposure, supporting their use as a safe alternative to estrogen-containing contraceptives in this patient population.

Keywords: Contraceptive agents; Estrogens; Hepatocellular adenoma; Progestins; Women's health.

Fig. 1.

Patient selection and cohort population. Sixty-one female patients were identified with hepatocellular adenoma. Exclusions were procedural intervention prior to follow-up scan (n = 17), absence of two or more scans (n = 7), or unknown type or duration of hormonal exposure (n = 10). Of the 27 patients meeting study criteria, distinct periods of hormone exposure were analyzed (some individuals had multiple discrete periods of hormone exposure were counted in each respective group). The total number of periods of with discrete nonoverlapping periods of hormone exposure was 34 (19 intervals without hormone exposure, seven periods of estrogen exposure, and eight periods of progestin-only exposure).

Fig. 2.

Change in sum of adenoma diameters from baseline to follow-up by hormonal exposure. Lines represent individual patients. Baseline imaging was designated as first scan available, and final imaging designated as last scan during period of exposure. (A) No hormone exposure (n = 19). (B) Estrogen exposure (n = 7). (C) Progestin-only exposure (n = 8). † Truncated at 5 years from first scan. ‡ Up to 15 milligrams oral norethindrone for menorrhagia. § hormonal intrauterine device.