Hormone replacement therapy after cervical cancer treatment: a Japanese claims-based cohort study

Only about one in five younger Japanese women treated for cervical cancer started hormone replacement therapy within six months of their primary treatment, according to a large analysis of a national insurance claims database, and those who did begin therapy tended to stop after roughly two years. The findings, drawn from more than 1,500 women treated between 2006 and 2024, point to what the researchers describe as a potential gap in survivorship care for a group at high risk of treatment-induced estrogen deficiency.

The study, published in BMC Women’s Health, used the JMDC claims database, which covers mainly employment-based insured persons and their dependents in Japan. The researchers included women aged 18 to 54 years who were diagnosed with cervical cancer from January 2006 to March 2024 and treated with surgery or radiotherapy. Their primary outcome was the initiation of hormone replacement therapy, or HRT, within six months of primary treatment. They estimated cumulative prescriptions over 72 months using the Kaplan–Meier method and assessed factors associated with HRT through multivariable logistic regression.

Of the 1,520 women included, 1,259 were treated with surgery and 261 with radiotherapy, and the median age was 44 years. In total, 334 women, or 22.0 percent, initiated HRT within six months. The rate was higher after surgery than after radiotherapy, at 23.4 percent versus 14.9 percent, and no woman aged 55 to 59 years initiated therapy. Use fell steeply with age, from 35.3 percent among those aged 18 to 34 years to 3.0 percent among those aged 50 to 54 years, and rose across treatment eras, from 16.7 percent to 23.9 percent.

Cumulative prescription over the longer follow-up period was significantly higher after surgery than after radiotherapy, and the two curves did not converge over 72 months. In the multivariable analysis, HRT initiation was associated with surgery, with an adjusted odds ratio of 2.52; with younger age, at an adjusted odds ratio of 0.91 per year of age; with concurrent chemotherapy, at an adjusted odds ratio of 2.05; and with more recent treatment era. The authors note that the odds ratios describe associations in this cohort rather than proven causal effects.

Among the women who did start HRT, treatment began early, at a median of 1.7 months after primary treatment. The regimens were predominantly transdermal and estrogen-only. Yet continuation was relatively short, with a median duration of about two years. The researchers suggest this pattern of early but brief use may reflect how HRT is discussed, prescribed and monitored in routine care rather than a deliberate, structured approach to managing estrogen deficiency after cancer treatment.

One finding drew particular attention from the authors. In the radiotherapy group, where the uterus is typically preserved, only 33 percent of HRT users received combination estrogen-progestin therapy. Because unopposed estrogen can stimulate the endometrium, the researchers flag this as a potential endometrial-protection concern that may warrant closer attention when prescribing HRT for women whose uterus remains in place after pelvic radiotherapy.

HRT plays a key role in maintaining quality of life in women with cancer treatment-induced estrogen deficiency, the authors write in the study background. Surgery and radiotherapy for cervical cancer can remove or damage the ovaries or impair their function, leaving women with sudden and sometimes severe estrogen deficiency at a young age. The study was designed to examine the real-world use of HRT among Japanese women with newly diagnosed cervical cancer who might experience this iatrogenic estrogen deficiency, rather than to test whether HRT itself improves outcomes.

The authors conclude that HRT prescription was uncommon in this claims-based cohort of younger women treated for cervical cancer, and that initiation was relatively short, suggesting a potential gap in survivorship care that warrants further investigation. They add that systematic assessment of ovarian status and structured counseling remain pragmatic targets for quality improvement. As an observational analysis of an insurance database covering mainly working-age insured women and their dependents, the study describes patterns of care in that population and does not establish why clinicians prescribed or withheld HRT in individual cases.

Subject of Research: Real-world use of hormone replacement therapy among younger Japanese women treated for cervical cancer, based on a national insurance claims database.

Article Title: Hormone replacement therapy after cervical cancer treatment: a Japanese claims-based cohort study

Article References: Gou, R., Fukuda, T., Tanaka, K., Ikeda, S., Tagaya, H., & Yoshino, O. (2026). Hormone replacement therapy after cervical cancer treatment: a Japanese claims-based cohort study. BMC Women's Health. https://doi.org/10.1186/s12905-026-05060-3

Image Credits: AI Generated

DOI: 10.1186/s12905-026-05060-3

Keywords: cervical cancer, hormone replacement therapy, estrogen deficiency, claims database, survivorship care, radiotherapy, surgery, transdermal estrogen, endometrial protection, Japan, cohort study, quality of life