A survey on treatment satisfaction with leuprorelin acetate in girls with central precocious puberty

Abstract.

Central precocious puberty (CPP) is often treated with gonadotropin-releasing hormone (GnRH) analogs to manage compromised adult height and psychological distress. In Japan, only monthly formulations are available, and the perceived burden and satisfaction associated with long-term treatment have not been well described. We conducted a retrospective questionnaire survey among 78 girls with CPP who received leuprorelin acetate between 2012 and 2018. Patients and caregivers were asked about reasons for treatment initiation, perceived burden, and satisfaction with height-related and psychological outcomes. Thirty-six (46%) participants completed the questionnaire. Although treatment was initiated at a mean age of 8.86 yr, when the height benefit was limited, improving final height was the most common reason for treatment initiation. Despite monthly injections over an average of 3 yr, 63.9% of the respondents reported no treatment burden. Satisfaction was high, with 72% of the participants satisfied with the height-related outcomes and 74% satisfied with the psychological outcomes. A greater absolute height at the time of the questionnaire was correlated with higher satisfaction in both domains. These findings do not imply that GnRH treatment improves final height. Instead, patients and caregivers reported high satisfaction despite the limited objective height benefits, underscoring the importance of thorough counseling, expectation management, and individualized decision making in CPP management.

Highlights

● Monthly GnRH treatment was associated with low treatment burden among girls with CPP.

● Patients and caregivers reported high satisfaction despite limited height benefits.

● Thorough counseling and expectation management were key contributors to perceived treatment value.

Introduction

Puberty is a complex biological process that involves a series of transformations, including the development of secondary sexual characteristics, rapid growth acceleration, and attainment of reproductive function. In girls, the onset of puberty at an abnormally early age is referred to as precocious puberty (1, 2). According to clinical standards in Japan, this condition is identified by the appearance of specific pubertal milestones before established age limits: breast development before 7.5 yr, appearance of pubic or axillary hair before 8 yr, and menarche before 10.5 yr of age (3). The main concerns with regards to central precocious puberty (CPP) are accelerated bone maturation by estrogen, which may lead to reduced adult height, and the psychological impact of entering puberty earlier than one’s peers (4,5,6). The decision to initiate CPP treatment is based on the consideration of these potential problems. Therapy involves gonadal suppression of the hypothalamic-pituitary-gonadal axis using gonadotropin-releasing hormone (GnRH) analog injections. While 3-mo and 6-mo depot GnRH agonist formulations are widely used in many countries and have been approved by the U.S. Food and Drug Administration (FDA) (7, 8), only monthly injections are available in Japan. There are no generally accepted criteria for treatment discontinuation, and the timing must therefore be individualized (9). Regarding adult height, treatment initiated before 6 yr of age can improve the final height (10), whereas treatment after 8 yr of age is unlikely to be effective (11,12,13). For girls whose puberty begins between 6 and 8 yr, treatment outcomes depend on the speed of pubertal progression and the degree of bone age advancement, and thus remain inconclusive (9). From a psychosocial perspective, early puberty has been associated with increased risks of anxiety, depression, behavioral difficulties, disordered eating, and risky behaviors in adolescence (14,15,16,17,18,19). Although some risks may lessen as peers undergo pubertal development, evidence remains limited on whether these findings apply to children with CPP or whether GnRH analog treatment alters these outcomes.

As treatment often requires repeated injections over several years, the burden on patients and their families is expected to be substantial. However, the actual extent of this treatment burden and the degree of satisfaction reported by patients and caregivers are understudied. To address this gap, we investigated the perceived burden and satisfaction associated with gonadotropin-releasing hormone analog therapy.

Methods

We retrospectively reviewed the medical records of 78 female patients with central precocious puberty who initiated treatment with leuprorelin acetate at our institution between October 2012 and March 2018 with continuous follow-up until the end of treatment.

Patients with congenital anomalies or tumors or had received medications known to affect adult height outcomes (e.g., GH or corticosteroids) were excluded.

A team-developed questionnaire was mailed to patients and their caregivers to assess whether they remained satisfied with GnRH therapy despite the uncertainty regarding the objective height benefits after long-term treatment. The questionnaire was specifically developed for this research purpose and not used in routine clinical practice, although its content was informed by clinical experience and prior literature on CPP and GnRH analog therapy. The questionnaire included items on patient’s background, reasons for treatment initiation, and treatment satisfaction, specifically regarding height-related and psychological outcomes (Supplementary Material). Treatment burden was assessed as an overall subjective perception encompassing injection-related discomfort, treatment duration, and injection frequency rather than a single factor.

While objectively confirmed adult height was not evaluated in this study, height-related outcomes were assessed based on patient-reported indicators, including growth cessation and patient height at the time of questionnaire completion. Patients who had not yet perceived growth cessation were also included in the analyses, based on their height at the time of the questionnaire.

The study protocol was reviewed and approved by the Ethics Committee of Osaka City General Hospital (Approval No.2304012). Written informed consent was obtained from all participants and their caregivers prior to completion of the questionnaire.

Results

Patient background

A total of 36 respondents (46%) completed the questionnaire. The patient background characteristics are summarized in Table 1. In response to the question regarding height growth (Q1), 27 participants (75%) reported that their linear growth had ceased (Table 1).

Table 1. Patient characteristics.

Treatment burden and daily life impact

Regarding treatment burden (Q2), 23 participants (64%) indicated that the treatment was not burdensome (Fig. 1). Regarding the impact on daily life (Q8), 33 participants (92%) indicated that CPP did not interfere with their daily activities.

Fig. 1.

Responses to the question, “Was the Leuprorelin injection burdensome?”. The pie chart illustrates the percentage of respondents who answered “Yes” (blue) or “No” (red) to the question regarding the burden of the leuprorelin injection.

Reasons for initiating treatment (Q3 and Q5)

Both patients and caregivers frequently cited “To improve final height” and “Menarche” as key reasons for initiating treatment. Additionally, many patients indicated that they started treatment based on parental recommendations. When asked about the most important reason for starting treatment, 69% of patients and 66% of caregivers selected “To improve final height” (Fig. 2), while the second most common reason was “Menarche” selected by 14% of patients and 31% of caregivers.

Fig. 2.

Reasons for initiating treatment. This bar chart shows the number of patients and caregivers who cited various reasons for deciding to initiate treatment. The reasons are categorized as follows: To improve final height, Menarche, Dislike of physical changes, Emotional instability, Being teased by friends, and Parental recommendation. The graph presents the frequency of each reason based on survey responses.

Treatment satisfaction (Q6)

Treatment satisfaction was defined as the proportion of respondents who selected “Very satisfied” or “Satisfied”. The overall satisfaction with the treatment was high with 72% of both patients and caregivers reporting satisfaction with height-related outcomes (Fig. 3). Furthermore, satisfaction with psychological outcomes was 74% among patients and 71% among caregivers (Fig. 3).

Fig. 3.

Patient and caregiver satisfaction with treatment outcomes. This bar chart presents the results of a five-point Likert scale survey on satisfaction with treatment outcomes. The responses are categorized by “Height-related aspect” and “Psychological aspect” showing the distribution of answers for each aspect: “Very satisfied,” “Satisfied,” “Neutral,” “Dissatisfied,” and “Very Dissatisfied”.

Although psychological dissatisfaction was not reported by either parents or caregivers, three patients rated “dissatisfied” regarding height outcomes. In two of these cases, their caregivers also reported dissatisfaction with height. In both cases, the patients did not reach their target height and free-text comments indicated a desire to achieve a greater final height.

Correlation between patient characteristics and satisfaction

Spearman’s rank correlation analysis showed that greater absolute height at the time of the questionnaire was significantly associated with higher satisfaction with both height-related and psychological outcomes among both patients and caregivers (p < 0.05) (Table 2). A higher target height was also significantly associated with greater satisfaction with height at the time of the questionnaire (p < 0.05) (Table 2).

Table 2. Correlation between treatment satisfaction and reason for treatment.

Additionally, among caregivers only, a greater difference between height at the time of the questionnaire and the target height was associated with higher satisfaction with regards to height outcomes (Table 2).

Effect of treatment duration

We further examined whether the treatment duration was associated with patient satisfaction. Among patients, treatment duration was not significantly correlated with satisfaction regarding height outcomes (r = −0.087, p = 0.616) but showed a significant negative correlation with psychological satisfaction (r = −0.343, p = 0.047).

Similarly, among caregivers, treatment duration was not correlated with height satisfaction (r = −0.105, p = 0.543) but was negatively correlated with psychological satisfaction (r = −0.343, p = 0.047). These findings suggest that longer treatment duration may be associated with lower psychological satisfaction despite comparable satisfaction with height outcomes.

Correlation between treatment satisfaction and reason for treatment

Patients and caregivers who prioritized “improvement in final adult height” as a reason for treatment initiation were more likely to report higher satisfaction with height outcomes (Table 3). In contrast, selection of “Menarche” as the primary reason for treatment initiation was not significantly associated with satisfaction (Table 3).

Table 3. Factors associated with satisfaction in height and psychological aspects after GnRH therapy in patients with CPP.

Effect of perceived treatment burden

No significant difference was observed in the satisfaction rates between those who perceived treatment as burdensome and those who did not (data not shown).

Discussion

Height-related factors influencing treatment satisfaction

In our survey, the most common reason for initiating GnRH analog therapy was concern about final adult height, as reported by 69.4% of patients and 65.7% of caregivers. Among patients, “being advised by their parents” was a frequent reason (13.9%) (Fig. 2). Regarding adult height, previous reports indicate that treatment after 8 yr is unlikely to be effective (11,12,13). In our survey, the mean age at treatment initiation was 8.86 yr (Table 1), an age at which treatment is generally not expected to result in a significant improvement in the final adult height. However, even after receiving this explanation, families still continued to choose the treatment primarily because of concerns about height. Although girls with CPP often present with a relatively tall stature at treatment initiation, this does not necessarily translate into improved height prognosis, and the present study does not demonstrate a treatment-induced increase in final height. Despite these limited expectations regarding objective height gain, more than 70% of both the patients and their caregivers reported being satisfied with height-related outcomes (Fig. 3). Importantly, satisfaction with height outcomes appeared to depend not only on absolute stature, but also on the extent to which patients and caregivers perceived that their expectations had been met. Correlation analyses demonstrated that greater height at the time of the questionnaire was associated with higher satisfaction with both height-related and psychological outcomes. Furthermore, satisfaction was influenced by how closely the current height approached the expected (target) height, particularly among the caregivers. Notably, dissatisfaction with height outcomes was reported by only a small number of patients and caregivers, and in these cases, free-text comments consistently indicated unmet expectations regarding the final stature. These findings suggest that dissatisfaction may be largely driven by discrepancies between anticipated and perceived outcomes rather than by treatment failure. The relatively small mean difference between the current and target height (−1.4 cm) suggests that many patients ultimately reached a height close to their anticipated goal, which may have contributed to the high overall satisfaction despite limited objective height benefit. Taken together, these findings underscore the importance of managing expectations regarding height outcomes when initiating GnRH therapy, particularly in patients who begin treatment after 8 yr of age. Although the expected benefit in height was limited in this study, the high level of treatment satisfaction likely reflected subjective and psychosocial factors, rather than an objective gain in height at the time of the questionnaire. These factors may include appropriate expectation management through counseling, reassurance associated with the suppression of pubertal progression, and psychological acceptance of treatment by patients and caregivers.

Treatment burden and its impact on satisfaction

Despite the need for monthly injections over an average treatment duration of 3 yr, 63.9% of the respondents reported that they did not perceive the therapy as burdensome (Fig. 1).

More than 90% of respondents indicated that CPP did not interfere with their daily activities. These findings suggest a relatively low perceived treatment burden, although only once-monthly injectable GnRH formulations are currently available in Japan. Several context-specific factors may explain the low perceived treatment burden observed in the present study. In Japan, public medical subsidies for children substantially reduce out-of-pocket medical costs, easing financial and psychological stress and lowering the perceived barriers to continuing regular clinic visits and injections, thereby contributing to the low reported treatment burden observed in this study. Interestingly, treatment duration was not associated with height satisfaction but was negatively correlated with psychological satisfaction among both patients and caregivers, suggesting cumulative psychological fatigue or evolving expectations over time, despite acceptable height outcomes. These findings underscore the need to monitor psychological well-being throughout long-term therapy. Future long-acting GnRH formulations may further reduce the treatment burden and improve psychological satisfaction and adherence. However, even with monthly injections, the overall treatment burden was lower than expected, suggesting that perceived burden is shaped by broader healthcare and social contexts as well as by treatment outcomes.

Psychological and social factors affecting satisfaction

Psychosocial concerns are often a major reason for seeking medical care in children with CPP, and families frequently worry about emotional instability, early menstruation, and negative peer experiences (20, 21). In our survey, over 70% of the patients and caregivers reported satisfaction with the psychological aspects of the treatment. However, the association between psychosocial concerns and satisfaction differed between the patients and caregivers. Among patients, concerns about being teased by peers were significantly associated with height-related satisfaction, whereas no such association was observed among caregivers. In patients, the association between fear of being teased and height-related satisfaction may reflect not only perceived stature, but also a psychological sense of protection afforded by treatment during vulnerable school years. Given the limited objective height benefits in this study, the reassurance derived from the suppression of pubertal progression and perceived social protection may have played a particularly important role in shaping satisfaction. This finding suggests that height may represent a particularly salient psychosocial factor in peer relationships from a patient’s perspective. Importantly, the psychological outcomes assessed in this study reflect subjective perceptions rather than objectively measured emotional or behavioral changes. Satisfaction with the psychological aspects of treatment may therefore reflect reassurance, relief from anxiety, or retrospective appraisal rather than true improvement in psychosocial functioning. Previous studies have suggested that the psychosocial distress associated with early puberty may diminish naturally as peers undergo pubertal development, regardless of treatment. Accordingly, although the high levels of reported psychological satisfaction are encouraging, these findings should be interpreted with caution (22, 23). Future prospective studies incorporating validated psychological and quality-of-life measures are required to clarify the true psychosocial impact of GnRH therapy in CPP.

Clinical implications and limitations

This study highlights the fact that high treatment satisfaction can be achieved even in the absence of clear objective height benefits, particularly when expectations regarding treatment outcomes are managed appropriately. These findings emphasize the importance of thorough counseling before treatment initiation, including clear communication regarding the expected height gain, treatment duration, and potential psychosocial effects.

This study has several limitations, including potential response bias, whereby families who were dissatisfied with treatment or discontinued therapy may have been underrepresented among respondents; the lack of a validated questionnaire; and the absence of standardized psychological assessments. Additionally, given the relatively small sample size and exploratory nature of the analyses, the findings should be interpreted as hypothesis-generating rather than confirmatory.

Despite these limitations, this study provides valuable insights into patient and caregiver perceptions of GnRH therapy for CPP in a real-world clinical setting. The results underscore the need for individualized decision-making, careful expectation management, and ongoing psychological support to optimize treatment satisfaction and the overall patient experience.

Conflict of interests

The authors have nothing to declare.