📄 other

Long-term prescribing patterns of hormone therapy and concomitant medications among women with menopausal disorders: a 20-year retrospective database study in Japan

This 20-year retrospective study of a Japanese university hospital database reveals a significant decline in hormone therapy prescribing for menopausal disorders among women aged 45–60, without a corresponding rise in psychotropic medications but with a modest increase in Kampo medicine use.

Original authors: Mutsuhiro Nakao, Hokuto Morohoshi, Yumiko Kurata, Akiou Nakamura

Published 2026-07-27

📖 4 min read☕ Coffee break read

CC BY 4.0

Original authors: Mutsuhiro Nakao, Hokuto Morohoshi, Yumiko Kurata, Akiou Nakamura

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Imagine your body is a bustling city that has been running on a very specific, high-octane fuel for decades. Around the time a woman reaches her late 40s or early 50s, the city's main power plant starts to wind down its production. This natural slowdown, called menopause, can cause the city's lights to flicker, the temperature to swing wildly, and the mood to become a bit stormy. For a long time, doctors had a "magic switch" they could flip to keep the lights on: hormone therapy. It was like plugging the city back into a steady power grid. But then, a massive report came out in 2002 that made everyone nervous about the safety of that switch. Suddenly, the city planners (doctors) started turning the switch off more often, wondering if there were better, safer ways to keep the lights from flickering. The big question became: as they turned off the old switch, did they start using a different kind of fuel, or did the city just learn to live with the dimmer lights?

This is exactly the story a team of researchers in Japan set out to investigate. They didn't just look at a few patients; they dug into a massive digital treasure chest containing over 8 million prescription records from a single university hospital, spanning a full 20 years (from 2002 to 2021). They were looking specifically at women between the ages of 45 and 60 who were dealing with the "stormy weather" of menopausal disorders. Their goal was to see how the prescription habits changed over two decades: Did doctors stop giving the "magic switch" (hormone therapy)? If they did, did they immediately start handing out "emergency batteries" like antidepressants or sleeping pills? Or did they turn to a traditional Japanese herbal remedy known as Kampo medicine, which is like a gentle, time-tested herbal tea for the body?

The researchers found that the "magic switch" (hormone therapy) was indeed being turned off significantly more often as the years went by. This matches what happened in many other countries after the big safety report. However, here is the twist: the city didn't just panic and grab the "emergency batteries." The use of strong psychiatric drugs—like antidepressants, anxiety relievers, and sleeping pills—did not skyrocket to fill the empty space left by the hormone therapy. The doctors didn't simply swap one heavy medication for another.

Instead, the data showed a slow, modest rise in the use of Kampo medicine. Think of Kampo as a reliable, gentle herbal companion that has been part of the Japanese medical landscape for a long time. The study found that women who were not getting the hormone therapy were slightly more likely to be prescribed these herbal remedies. But the researchers are careful to say this doesn't mean the herbal tea replaced the hormone switch in a direct swap. It's more like the doctors were exploring different tools in their toolbox.

The study also looked at who was getting the hormone therapy and who wasn't. They found that women who were younger (between 50 and 55) and those visiting the gynecology department were more likely to still be getting the hormone treatment. Interestingly, women who were already taking drugs for heart or metabolism issues were less likely to get the hormone therapy, perhaps because their doctors were being extra cautious.

In the end, this 20-year look at the prescription records tells us that the medical world has shifted its approach. The "magic switch" is used much less frequently now, but the city hasn't just switched to a different heavy-duty medication. Instead, there's a quiet, steady trend toward using traditional herbal remedies alongside other treatments. The researchers admit they can't see the patients' actual symptoms or hear their personal stories from these digital records, so they can't say for sure why every doctor made their choice. But this long-term view gives us a clear picture of how real-world medicine is evolving: moving away from the old standard, but not necessarily rushing to a single new replacement, instead trying a mix of approaches to help women navigate their changing years.

Technical Summary: Long-term Prescribing Patterns of Hormone Therapy and Concomitant Medications in Japan

Problem Statement
Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms associated with menopause, yet its utilization has shifted significantly following the 2002 Women's Health Initiative (WHI) report. While international guidelines have evolved to support HT for specific populations (e.g., women within 10 years of menopause or under age 60), real-world prescribing data in Japan regarding long-term trends and concomitant medication usage remains limited. In routine clinical practice, women with menopausal disorders often receive a spectrum of non-HT medications, including psychotropics, Kampo medicine (traditional Japanese herbal medicine), and cardiometabolic drugs. The study addresses the gap in understanding how HT prescribing patterns have evolved over two decades in Japan and whether declines in HT have been paralleled by increases in alternative pharmacological treatments.

Methodology
The authors conducted a 20-year retrospective database study (April 1, 2002 – March 31, 2022) utilizing electronic prescription records from a single tertiary university hospital in a metropolitan area of Japan. The study encompassed 8,374,408 prescriptions issued to 180,226 female patients.

The analysis employed two complementary approaches:

Prescription-level Analysis: This described annual prescribing prevalence for HT and six concomitant medication categories (SSRIs/SNRIs, anxiolytic benzodiazepines, hypnotics, Kampo medicine, cardiometabolic drugs, and osteoporosis drugs) across the entire female population. Temporal trends were evaluated using the Cochran–Armitage trend test.
Patient-level Analysis: Focusing on women aged 45–60 years with ICD-10-coded menopausal disorders (N95.1), the study identified 1,167 unique women. Patients were classified as HT users (received at least one HT prescription) or non-users. Multivariable logistic regression was used to identify factors associated with ever receiving HT, adjusting for department group, age, inpatient/outpatient status, and calendar period.

Key Contributions

Long-term Real-World Evidence: The study provides a rare, two-decade longitudinal view of prescribing patterns in a Japanese tertiary care setting, capturing the post-WHI era transition.
Concomitant Medication Trends: Unlike previous studies focusing solely on HT, this research simultaneously tracks the temporal trends of major concomitant medication categories, including the specific role of Kampo medicine in menopausal care.
Multivariable Characterization: The study moves beyond simple trend description to identify patient-level characteristics (e.g., department, age, comorbidity proxy via drug use) independently associated with HT utilization.

Results

Overall Trends: Among the 1,167 women with menopausal disorders, 268 (23.0%) received HT. HT prescribing declined significantly over the 20-year period ( $p < 0.001$ ).
Concomitant Medications:
- Psychotropics: Prescribing of SSRIs/SNRIs, anxiolytic benzodiazepines, and hypnotics did not show a corresponding increase to offset the decline in HT. In fact, the overall prevalence of psychotropic drugs among female patients decreased significantly over the study period.
- Kampo Medicine: Prescribing showed a modest but significant increasing trend ( $p < 0.001$ ).
- Other Categories: Cardiometabolic and osteoporosis drug prescribing also increased significantly.
Patient-Level Associations: In multivariable logistic regression, the use of Kampo medicine was inversely associated with HT use (Odds Ratio [OR] 0.838; 95% CI 0.768–0.915), suggesting Kampo was more likely to be prescribed in the absence of HT. Conversely, the use of cardiometabolic drugs was associated with a lower likelihood of receiving HT (OR 0.619). Patients in the Obstetrics and Gynecology department and those aged 50–55 were more likely to receive HT compared to other groups.

Significance and Claims
The paper claims to describe real-world prescribing patterns that reflect the complex interplay between evolving clinical guidelines, physician preferences, and patient characteristics in Japan. The authors assert that the significant decline in HT was not accompanied by a parallel rise in psychotropic medications, challenging the assumption that antidepressants or anxiolytics simply replaced HT in this population. While Kampo medicine showed an inverse relationship with HT, the study explicitly states it cannot determine if Kampo replaced HT or was prescribed for different indications due to the lack of symptom severity data.

The authors conclude that these findings contribute to a better understanding of routine clinical practice in Japan. They emphasize that the results should be interpreted cautiously, as the database lacks data on treatment indications, symptom severity, and patient preferences. The study positions itself as a foundational descriptive report intended to inform future multicenter and population-based studies evaluating the pharmacological management of menopausal symptoms.

Technical Summary: Long-term Prescribing Patterns of Hormone Therapy and Concomitant Medications in Japan

More like this