Abstract
Objective:
Fezolinetant (Veozah) was approved as a non-hormone treatment for moderate-to-severe vasomotor symptoms of menopause in May 2023, providing a novel treatment option for women with contraindications to menopausal hormone therapy. The objective of the study was to characterize the uptake and utilization of fezolinetant in a real-world setting.
Methods:
We conducted a retrospective cohort study using TriNetX data, which includes 69 healthcare organizations and over 60 million patients. Females with an initial prescription for fezolinetant between May 1, 2023, and December 31, 2024, were included. We described baseline clinical and demographic characteristics and assessed the uptake in fezolinetant over time.
Results:
Our cohort included 9,853 women, including 1,315 (13.3%) who were over the age of 65 and 2,022 (20.5%) with a breast cancer diagnosis. Among the 7,222 individuals with at least three months of continuous enrollment, 1,477 (20.5%) had persistent use, defined as having a second fezolinetant prescription between 28 and 90 days of the initial fezolinetant prescription. Among persistent users, 42% received liver function testing in the three months after initiating fezolinetant, though regular monitoring is required after starting treatment. The total number of fezolinetant prescriptions increased over time, from 233 prescriptions between May 1 through July 31, 2023, to 1,871 prescriptions between May 1 and July 31, 2024.
Conclusions:
Our findings highlight a need for future post-marketing safety and effectiveness studies, especially among survivors of breast cancer and women 65 years and older, who were excluded from the randomized controlled trials.
Keywords: non-hormone therapy, fezolinetant, menopause, vasomotor symptoms
Background
Each year, over one million women in the United States enter menopause, and an estimated 34% to 80% of these women experience moderate-to-severe vasomotor symptoms, including hot flashes and night sweats.1–4 Menopause symptoms can significantly affect women’s quality of life, including sleep, work, mood, energy levels, sexual activity, and social and leisure activities.5–7 Menopause symptoms can be persist for years, and the Study of Women’s Health Across the Nation (SWAN) found that women experienced a median of 7.4 years of vasomotor symptoms during the menopause transition period.8 While hormone therapy is recommended for the treatment of vasomotor symptoms, it is often underutilized due to patient and provider concerns about elevated risk of cancer and heart disease.9 Hormone therapy is also contraindicated in women with the following conditions: prior estrogen-sensitive cancer, including breast cancer; liver disease; unexplained vaginal bleeding; prior coronary heart disease, stroke, myocardial infarction, or venous thromboembolism; and history or high risk of thromboembolic disease.10,11
In May 2023, the U.S. Food and Drug Administration (FDA) approved fezolinetant (Veozah) for the treatment of moderate-to-severe vasomotor symptoms (VMS) of menopause.5 Fezolinetant, a novel non-hormone neurokinin 3 receptor antagonist, is a first-in-class medication that crosses the blood-brain barrier and regulates neural activity in the thermoregulatory center to provide relief from hot flashes and night sweats.5 Randomized controlled trial data from the SKYLIGHT 1 and 2 studies suggest the safety and efficacy of fezolinetant for improving moderate-to-severe VMS, quality of life, and sleep disturbances.12–15 The SKYLIGHT 4 study found that roughly 2% of patients receiving fezolinetant had elevated liver enzyme levels more than three times the upper limit of normal.5 Fezolinetant is contraindicated in individuals with a history of cirrhosis, and the FDA has also added a black box warning about the risk of serious liver injury and recommends hepatic laboratory testing at baseline and at months 1, 2, 3, 6, and 9 after initiating treatment.16
As a non-hormone option, fezolinetant is a groundbreaking treatment option that has profound implications for improving quality of life for individuals who are unable to utilize hormone therapy for menopause symptoms.12 Generally, older women are not recommended to initiate hormone therapy, given the elevated risk for cardiovascular disease associated with initiating oral, systemic hormone therapy in this population.17,18 The 2022 Hormone Therapy Position Statement of the North American Menopause Society states that the risks of initiating hormone therapy may outweigh the benefits for women 60 years and older, though women currently receiving hormone therapy may continue treatment beyond 65 years old, with necessary risk assessments and counseling. The American Geriatrics Society’s Beers Criteria warns against the use of hormone therapy in women over the age of 65.11 However, menopause symptoms can significantly affect women’s quality of life long after the natural age of menopause.19
Treatment options for vasomotor symptoms are also limited for those with a history of breast cancer, as hormone therapy is associated with an increased risk of recurrence in survivors of breast cancer, especially those with hormone receptor positive breast cancer.20,21 The management of vasomotor symptoms is a largely unmet need in these patients, and survivors of breast cancer entering premature menopause following cancer treatment often experience more severe menopause symptoms than women entering menopause naturally.22,23 Prior to the approval of fezolinetant, the only approved non-hormone medication for moderate-to-severe vasomotor symptoms was paroxetine mesylate 7.5mg, an antidepressant shown to provide modest relief from hot flashes.24–26
To our knowledge, no studies have been conducted on the real-world utilization of fezolinetant. Therefore, the objectives of this study were to characterize fezolinetant use, with a special focus on populations under-represented or not included in the SKYLIGHT studies—individuals over 65 years of age and individuals with a history of breast cancer.
Methods
This retrospective cohort study was conducted using TriNetX data. Updated every 2–4 weeks, the TriNetX data’s Research Network encompasses 108 healthcare organizations in the United States and includes over 156 million participants.27 The database includes insurance claims data with diagnosis and procedural codes, electronic medical record data, and laboratory results.27 Clinical information from physician notes and reports are extracted using Natural Language Processing algorithms and made available in the TriNetX data.27
We identified female participants with an initial prescription for fezolinetant (RxNorm code 2637134) between May 1, 2023, and December 31, 2024. Younger women were included in our cohort to ensure that we would capture individuals experiencing premature menopause after treatment for breast cancer. We created the following three sub-cohorts to reflect the average age of menopause in the United States (i.e., 51 years old) and to allow for better comparison to the SKYLIGHT trials, which used an age cut-off of 65 years old: ≤50 years old, 51–65 years old, and ≥66 years old.
We also created a breast cancer sub-cohort, consisting of women with a code for breast cancer or breast cancer history (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes C50 and Z85.3) prior to the initiation of fezolinetant. We further stratified this cohort by age when presenting the results: ≤65 and ≥66 years old. To examine persistent fezolinetant use, we also identified a sub-cohort with at least 90 days of follow-up, defined as a clinic visit in the three months after fezolinetant initiation. Among this group, we identified persistent users who had a second fezolinetant prescription between 28 and 90 days of the initial fezolinetant prescription. The timeframe was chosen to allow for a grace period for the prescription refill.
To characterize the cohort and sub-cohorts, demographic variables such as age, race/ethnicity, and geographic location were assessed. Relevant clinical variables and baseline medical history were also examined, using all-available look-back (e.g., deep vein thrombosis, pulmonary embolism, cardiovascular disease, liver disease, hypertension, nicotine use, body mass index). We also examined the number of new fezolinetant prescriptions prescribed between May 1, 2023, and January 31, 2025, using 3-month intervals, to assess the change in uptake of fezolinetant over time (Figure 1).
Figure 1.
Quarterly trend in fezolinetant prescriptions, from May 1, 2023, and January 31, 2025.
As the TriNetX platform uses deidentified data and only provides aggregated counts, the Institutional Review Board at our institution has deemed the use of TriNetX data exempt from review. We conducted analyses on August 4, 2025. For all results, cell sizes between 1 and 10 were suppressed to comply with the minimum cell size policy.
Results.
Descriptive Statistics.
We identified 9,853 women who initiated fezolinetant between May 1, 2023, and December 31, 2024. The mean age of the cohort was 55.3 years (Standard Deviation 8.9 years), with 2,675 (27.1%) who were ≤50 years old, 5,863 (59.5%) who were 51–65 years old, and 1,315 (13.3%) who were ≥66 years old. The majority of fezolinetant initiators were White (72.5%), and 16.4% were Black or African American. Our cohort was geographically diverse, with 40% in the South, 23% in the West, 19% in the Midwest, and 19% in the Northeast. For the persistent users, however, the majority resided in the West (55%), followed by 18% in the South, 16% in the Midwest, and 11% in the Northeast. Using all-available data to examine baseline conditions, we found that chronic diseases were prevalent: 30.0% had hyperlipidemia, 37.4% had hypertension, 12.7% had type 2 diabetes mellitus, and 19.2% had hypothyroidism. Mental health conditions were also common: 42.6% had anxiety, 29.9% had a depressive episode, and 10.5% had recurrent major depressive disorder. Additionally, one in five individuals in the overall cohort had a code for any migraine (22.3%), a relative contraindication to hormone therapy. We found that the mean body mass index (BMI) was 29.5 kg/m2, which falls in the overweight and borderline obese range, according to the Centers for Disease Control and Prevention categories for overweight (BMI 25–29.9) and obesity (BMI 30+),28 and 22.5% of the cohort had a code for obesity (Table 1).
Table 1.
Characteristics of individuals initiating fezolinetant, overall and by age group (N,%).
| Characteristic Name | Overall | ≤50 years old | 51–65 years old | ≥66 years old |
|---|---|---|---|---|
| Total | 9,853 | 2,675 | 5,863 | 1,315 |
| Age at Index (mean, std) | 55.3 (8.9) | 45.6 (4.7) | 56.2 (4.0) | 71.2 (4.7) |
| Race | ||||
| American Indian or Alaska Native | 50 (0.5) | 21 (0.8) | 19 (0.3) | 10 (0.8) |
| Asian | 155 (1.6) | 55 (2.1) | 84 (1.4) | 16 (1.2) |
| Black or African American | 1616 (16.4) | 467 (17.5) | 991 (16.9) | 158 (12) |
| Native Hawaiian or Other Pacific Islander | 32 (0.3) | ≤10 (0.4) | 12 (0.2) | ≤10 (0.8) |
| White | 7,146 (72.5) | 1,858 (69.5) | 4,233 (72.2) | 1,055 (80.2) |
| Multi-racial or race not listed | 344 (3.5) | 116 (4.3) | 198 (3.4) | 30 (2.3) |
| Unknown Race | 529 (5.4) | 151 (5.7) | 326 (5.6) | 52 (4) |
| Ethnicity | ||||
| Hispanic or Latino | 571 (5.8) | 220 (8.2) | 312 (5.3) | 39 (3) |
| Not Hispanic or Latino | 7,446 (75.6) | 1,909 (71.4) | 4,480 (76.4) | 1,057 (80.4) |
| Unknown Ethnicity | 1,836 (18.6) | 546 (20.4) | 1,071 (18.3) | 219 (16.7) |
| Baseline conditions | ||||
| Hyperlipidemia | 2,958 (30) | 541 (20.2) | 1,728 (29.5) | 689 (52.4) |
| Hypertensive diseases | 3,684 (37.4) | 780 (29.2) | 2,146 (36.6) | 758 (57.6) |
| Type 2 diabetes mellitus | 1,255 (12.7) | 299 (11.2) | 730 (12.5) | 226 (17.2) |
| Chronic kidney disease (CKD) | 386 (3.9) | 82 (3.1) | 173 (3) | 131 (10) |
| Obesity | 2,220 (22.5) | 664 (24.8) | 1,271 (21.7) | 285 (21.7) |
| Hypothyroidism | 1,887 (19.2) | 393 (14.7) | 1,093 (18.6) | 401 (30.5) |
| Hyperthyroidism | 335 (3.4) | 80 (3) | 193 (3.3) | 62 (4.7) |
| Anxiety and other nonpsychotic mental disorders | 4,202 (42.6) | 1,306 (48.8) | 2,334 (39.8) | 562 (42.7) |
| Major depressive disorder, recurrent | 1,035 (10.5) | 309 (11.6) | 565 (9.6) | 161 (12.2) |
| Depressive episode | 2,942 (29.9) | 889 (33.2) | 1,621 (27.7) | 432 (32.9) |
| Migraine | 2,193 (22.3) | 738 (27.6) | 1,245 (21.2) | 210 (16) |
| Chronic pain | 3,181 (32.3) | 841 (31.4) | 1,815 (31) | 525 (39.9) |
| Sleep disorders | 3,222 (32.7) | 843 (31.5) | 1,864 (31.8) | 515 (39.2) |
| Nicotine dependence | 1,267 (12.9) | 457 (17.1) | 696 (11.9) | 114 (8.7) |
| Alcohol related disorders | 294 (3) | 101 (3.8) | 161 (2.8) | 32 (2.4) |
| BMI in kg/m2 | ||||
| BMI information available | 7,534 (76.5) | 2,109 (78.8) | 4,388 (74.8) | 1,037 (78.9) |
| BMI (mean, std) | 29.5 (6.7) | 30.1 (7.1) | 29.4 (6.6) | 28.4 (6.0) |
std: standard deviation
Counts under 11 were suppressed for data privacy.
We identified 2,022 (20.5%) individuals with a breast cancer diagnosis prior to initiating fezolinetant, 1,698 (84.0%) of whom were ≤65 years old and 324 (19.1%) were ≥66 years old. Among those with breast cancer history, nearly half of individuals had a code for anxiety or other non-psychotic mental health disorder at baseline (49.2%), 39% had insomnia or sleep disorders, and 33.6% had chronic pain. The majority of those with breast cancer history were ≤65 years old, and the mean age at fezolinetant initiation was 54.9 years (standard deviation, 10.3 years) (Table 2). We also identified 7,722 (78.4%) individuals who had continuous enrollment for at least 90 days. Among those with at least 90 days of enrollment, we found that only 1,477 (19.1%) had a second prescription between 30 and 90 days after the initial one, while 6,245 (80.9%) did not have a second prescription during that period (Table 3). We also assessed utilization of liver function tests among persistent users and found that 42% of persistent users had liver function testing in the three months after initiating fezolinetant.
Table 2.
Characteristics of breast cancer survivors initiating fezolinetant, overall and by age group.
| Characteristic Name | Breast cancer history | Breast cancer history, ≤65 years old | Breast cancer history, ≥66 years old |
|---|---|---|---|
| Total | 2,022 | 1,698 | 324 |
| Age at Index (mean, std) | 54.9 (10.3) | 51.7 (7.6) | 71.6 (4.7) |
| Race | |||
| American Indian or Alaska Native | ≤10 (0.5) | ≤10 (0.6) | ≤10 (3.1) |
| Asian | 50 (2.5) | 47 (2.8) | ≤10 (3.1) |
| Black or African American | 217 (10.7) | 188 (11.1) | 29 (9) |
| Native Hawaiian or Other Pacific Islander | ≤10 (0.5) | ≤10 (0.6) | 0 (0) |
| White | 1,559 (77.1) | 1,288 (75.9) | 271 (83.6) |
| Multi-racial or race not listed | 80 (4) | 72 (4.2) | ≤10 (3.1) |
| Unknown Race | 101 (5) | 89 (5.2) | 12 (3.7) |
| Ethnicity | |||
| Hispanic or Latino | 120 (5.9) | 115 (6.8) | ≤10 (3.1) |
| Not Hispanic or Latino | 1,570 (77.6) | 1,297 (76.4) | 273 (84.3) |
| Unknown Ethnicity | 332 (16.4) | 286 (16.8) | 46 (14.2) |
| Baseline conditions | |||
| Hyperlipidemia | 591 (29.2) | 418 (24.6) | 173 (53.4) |
| Hypertensive diseases | 751 (37.1) | 556 (32.7) | 195 (60.2) |
| Type 2 diabetes mellitus | 236 (11.7) | 177 (10.4) | 59 (18.2) |
| Chronic kidney disease (CKD) | 64 (3.2) | 43 (2.5) | 21 (6.5) |
| Obesity | 471 (23.3) | 396 (23.3) | 75 (23.1) |
| Hypothyroidism | 419 (20.7) | 324 (19.1) | 95 (29.3) |
| Hyperthyroidism | 85 (4.2) | 70 (4.1) | 15 (4.6) |
| Anxiety and other nonpsychotic mental disorders | 994 (49.2) | 836 (49.2) | 158 (48.8) |
| Major depressive disorder, recurrent | 215 (10.6) | 178 (10.5) | 37 (11.4) |
| Depressive episode | 650 (32.1) | 529 (31.2) | 121 (37.3) |
| Migraine | 432 (21.4) | 380 (22.4) | 52 (16) |
| Chronic pain | 680 (33.6) | 553 (32.6) | 127 (39.2) |
| Sleep disorders | 788 (39) | 647 (38.1) | 141 (43.5) |
| Nicotine dependence | 229 (11.3) | 200 (11.8) | 29 (9) |
| Alcohol related disorders | 81 (4) | 66 (3.9) | 15 (4.6) |
| BMI in kg/m2 | |||
| BMI information available | 1,717 (84.9) | 1,438 (84.7) | 279 (86.1) |
| BMI (mean, std) | 28.6 (6.3) | 28.7 (6.3) | 27.9 (6.1) |
std: standard deviation
Counts under 11 were suppressed for data privacy.
Table 3.
Characteristics of individuals with at least three months of continuous enrollment, overall and by persistence of fezolinetant use (N,%).
| Characteristic Name | Total with 3 months cont. enrollment | Persistent | Discontinued |
|---|---|---|---|
| Total | 7,722 | 1,477 | 6,245 |
| Age at Index (mean, std) | 55.4 (9.0) | 55.0 (8.8) | 55.5 (9.0) |
| Race | |||
| American Indian or Alaska Native | 37 (0.4) | 11 (0.5) | 26 (0.4) |
| Asian | 144 (1.6) | 28 (1.4) | 116 (1.7) |
| Black or African American | 1,414 (16.1) | 275 (13.5) | 1,139 (16.9) |
| Native Hawaiian or Other Pacific Islander | 20 (0.2) | ≤10 (0.5) | 17 (0.3) |
| White | 6,410 (73.1) | 1,514 (74.5) | 4,896 (72.7) |
| Multi-racial or race not listed | 304 (3.5) | 87 (4.3) | 217 (3.2) |
| Unknown Race | 439 (5) | 113 (5.6) | 326 (4.8) |
| Ethnicity | |||
| Hispanic or Latino | 514 (5.9) | 150 (7.4) | 364 (5.4) |
| Not Hispanic or Latino | 6,686 (76.3) | 1,641 (80.8) | 5,045 (74.9) |
| Unknown Ethnicity | 1,568 (17.9) | 240 (11.8) | 1,328 (19.7) |
| Baseline conditions | |||
| Hyperlipidemia | 2,806 (32) | 651 (32.1) | 2,155 (32) |
| Hypertensive diseases | 3,454 (39.4) | 781 (38.5) | 2,673 (39.7) |
| Type 2 diabetes mellitus | 1,180 (13.5) | 275 (13.5) | 905 (13.4) |
| Chronic kidney disease (CKD) | 377 (4.3) | 89 (4.4) | 288 (4.3) |
| Obesity | 2,110 (24.1) | 497 (24.5) | 1,613 (23.9) |
| Hypothyroidism | 1,782 (20.3) | 450 (22.2) | 1,332 (19.8) |
| Hyperthyroidism | 314 (3.6) | 95 (4.7) | 219 (3.3) |
| Anxiety and other nonpsychotic mental disorders | 3,961 (45.2) | 965 (47.5) | 2,996 (44.5) |
| Major depressive disorder, recurrent | 979 (11.2) | 269 (13.2) | 710 (10.5) |
| Depressive episode | 2,784 (31.8) | 702 (34.6) | 2,082 (30.9) |
| Migraine | 2,048 (23.4) | 569 (28) | 1,479 (22) |
| Chronic pain | 3,011 (34.3) | 759 (37.4) | 2,252 (33.4) |
| Sleep disorders | 3,054 (34.8) | 822 (40.5) | 2,232 (33.1) |
| Nicotine dependence | 1,187 (13.5) | 263 (12.9) | 924 (13.7) |
| Alcohol related disorders | 276 (3.1) | 67 (3.3) | 209 (3.1) |
| BMI in kg/m2 | |||
| BMI information available | 6,820 (77.8) | 1,605 (79.0) | 5,215 (77.4) |
| BMI (mean, std) | 29.5 (6.7) | 28.8 (6.2) | 29.7 (6.8) |
std: standard deviation
Counts under 11 were suppressed for data privacy.
Regarding baseline liver conditions, 6.8% of our cohort had a code indicative of metabolic dysfunction-associated steatotic liver disease (MASLD), previously called nonalcoholic fatty liver disease (NAFLD), and 0.7% had a code for nonalcoholic steatohepatitis (NASH). Additionally, we examined the history of cardiac conditions, as these are often contraindications for hormone therapy use. Among the overall cohort, 7.0% had a code for chronic ischemic heart disease. Few women had a history of venous thromboembolism (3.9%) or transient ischemic attack (2.3%) (Table 4). Roughly 15% of the cohort had a code signifying the acquired absence of the uterus.
Table 4.
Baseline conditions that are absolute or relative contraindications to hormone therapy or fezolinetant, among patients initiating fezolinetant (N,%).
| Characteristic Name | Total |
|---|---|
| Baseline liver conditions | |
| Nonalcoholic steatohepatitis (NASH) | 67 (0.7) |
| Fatty (change of) liver (MASLD) | 674 (6.8) |
| Chronic hepatitis | 30 (0.3) |
| Contraindications to hormone therapy | |
| Breast cancer history | 2,022 (20.5) |
| Coagulation defects, purpura and other hemorrhagic conditions | 607 (6.2) |
| Acute myocardial infarction | 168 (1.7) |
| Angina pectoris | 180 (1.8) |
| Chronic ischemic heart disease | 689 (7) |
| Other acute ischemic heart diseases | 50 (0.5) |
| Cerebral infarction | 272 (2.8) |
| Personal history of venous thrombosis and embolism | 381 (3.9) |
| Personal history of transient ischemic attack (TIA), and cerebral infarction without residual deficits | 231 (2.3) |
| Phlebitis and thrombophlebitis | 124 (1.3) |
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously nonalcoholic fatty liver disease (NAFLD)
Lastly, we depicted the 3-month counts of fezolinetant prescriptions between May 1, 2023, and January 31, 2025. The number of first-time prescriptions for fezolinetant increased from 233 prescriptions in the May 1, 2023, through July 31, 2023, period to 1,871 prescriptions in the May 1, 2024, to July 31, 2024, period (Figure 1).
Discussion.
Our study provides valuable insights into a real-world population of early fezolinetant initiators, especially groups that were excluded from the SKYLIGHT trials.12 In our study, 13.3% were ≥66 years old at the time of fezolinetant initiation, suggesting a need for future studies focusing on menopause symptom management in older women. Two large, prospective longitudinal studies have demonstrated that vasomotor symptoms can persist approximately 10 years after menopause in at least a quarter of women.18 In a study including 4,956 women presenting for menopause consultation at the Mayo Clinic, investigators found that 18% of women were 60 years and older, among which 41% experienced moderate-to-severe vasomotor symptoms of menopause.19 In the SKYLIGHT trials, though an age cutoff of 66 years was used, ~11% of individuals were between the ages of 60 through 65.12 Menopause symptoms affect a substantial group of older adults, and these symptoms should not be overlooked.
Individuals with a history of breast cancer comprised 20.5% of our cohort. The initial adoption of fezolinetant among individuals with a history of breast cancer despite the absence of clinical trial data highlights the large gap that fezolinetant fills in providing a non-hormone treatment option for survivors of breast cancer experiencing menopause symptoms. In a recent survey study with over 1,000 women with a breast cancer history, nearly all women experienced menopause symptoms (99.7%) and expressed their need for more support in addressing those symptoms (96%).29 Glynne and colleagues similarly found that most women undergoing premature menopause after breast cancer treatment felt uninvolved in treatment decisions around their menopause symptoms.29
Recently, the HIGHLIGHT 1 study, a randomized, placebo-controlled trial, began evaluating the safety and efficacy of fezolinetant used in patients with hormone receptor-positive breast cancer receiving adjuvant endocrine therapy. While future research is needed to assess the long-term safety and effectiveness of fezolinetant use in individuals with breast cancer and breast cancer history, it is promising that there is no currently determined or notable biological rationale suggesting an increased risk of breast cancer recurrence with fezolinetant use. As non-hormone menopause therapy options like fezolinetant become available, it is important that patients with breast cancer or breast cancer history are appropriately counseled and involved in treatment decisions for managing their menopause symptoms.
Notably, we also found a high proportion of the overall cohort discontinuing fezolinetant: 6,245 out of 7,722 individuals (80.9%) of those with at least three months of continuous enrollment did not have a second fezolinetant prescription between 28 and 90 days after the initial prescription. While we are unable to identify the causes of discontinuation, some common causes for drug discontinuation generally include side effects and adverse events, lack of efficacy, drug interactions, and high drug co-pay costs. As fezolinetant is associated with elevated liver function tests and hepatotoxicity in some individuals,30 the frequent liver function testing may also make adherence difficult. More research is needed to investigate patients’ access to liver function testing and adherence to the recommended intervals for hepatic laboratory testing (i.e., at baseline and months 1, 2, 3, 6, and 9 after starting treatment).
Barriers to initiating fezolinetant must also be considered. Between May 1, 2023, through July 31, 2024, we found an increasing number of new fezolinetant prescriptions in each 3-month interval, after which we noted a decline in new prescriptions. Fezolinetant uptake may be hindered by the extensive hepatic monitoring required, as it can be costly, time-consuming, and unpleasant for patients to adhere to the recommended monitoring schedule. Patients and providers may also be more cautious as fezolinetant is a new medication without long-term safety data. As with menopausal hormone therapy, patients may have concerns about potential risks with treatment or encounter financial barriers, whether with cost or lack of insurance.31
This study has several strengths. With the TriNetX data updated every 2–4 weeks, we were able to assess the utilization of this recently approved medication. Additionally, as TriNetX includes healthcare organizations across the United States, and we were able to obtain a geographically diverse cohort of fezolinetant initiators. This study is novel, as it is the first study to assess fezolinetant use in a real-world population and to provide important insights into its use in populations that have contraindications to hormone therapy. Recently, a randomized placebo-controlled trial (DAYLIGHT) was conducted, including women deemed unsuitable for hormone therapy (contraindication, use with caution, averse, or prior discontinuation).32 However, only 226 women were randomized to the fezolinetant group, including women with contraindications.32 In contrast, using the TriNetX data, we were able to capture a large cohort of fezolinetant initiators, including women with cancer history and other contraindications.
Despite these strengths, a limitation of this study is the short follow-up time, as fezolinetant was only approved in May 2023. Additionally, the claims data only indicate a prescription for fezolinetant, not administration or receipt of the medication. However, we included a sub-cohort of persistent users who had a second fezolinetant prescription between 28 and 90 days after the first prescription, thereby suggesting receipt and utilization of fezolinetant.
Conclusion.
The uptake of fezolinetant underscores a previously unmet need, as many women in our cohort had baseline conditions that were relative or absolute contraindications to using hormone therapy. Our study characterizes the use of fezolinetant and identifies several key areas for future research.
Sources of funding
Drs. Hsu and Adekanmbi are supported by a research career development award (K12AR084228: Building Interdisciplinary Research Careers in Women’s Health Program-BIRCWH; Berenson, PI) from the National Institutes of Health/Office of the Director (OD) and National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Footnotes
Financial disclosures/conflicts of interest
The authors have no conflicts of interest to disclose.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
National conference: this abstract has been accepted for a poster presentation at the International Society for Pharmacoepidemiology annual meeting in August 2025.
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