Sexual dysfunction in Brazilian women undergoing adjuvant endocrine therapy for breast cancer: prevalence and associated factors

Abstract

This study aimed to describe the frequency of sexual dysfunction among women undergoing adjuvant endocrine therapy (ET) and explore its relationship with patients’ clinical, social, and demographic characteristics. We evaluated women with a history of non-metastatic estrogen receptor-positive invasive breast carcinoma who had been receiving adjuvant ET for at least 6 months and reported at least one instance of sexual intercourse 4 weeks prior to study entry. Sexual dysfunction was assessed using the Female Sexual Function Index (FSFI). Demographic and medical information were extracted from medical records and data were analyzed using R software. Between June 2021 and March 2024, a total of 774 patients were recruited. The mean age was 56.5 years. The mean duration of ET was 3.2 years. Only 346 patients (44.8%) had engaged in sexual intercourse in the previous 4 weeks and among them, 276 (79.8%) reported sexual dysfunction (mean FSFI score = 20.83, standard deviation SD = 6.3). Patient with sexual dysfunction were older than those without (53 ± 10.4 vs. 48 ± 9.4 p = 0.0002) and exhibited significantly lower EORTC QLQ C30 and BR23 scores. The use of aromatase inhibitors (AI) versus tamoxifen was associated with sexual dysfunction, with a prevalence ratio of 1.17 for sexual dysfunction (p = 0.047). In this study 79.8% of patients experienced sexual dysfunction. Interventions, such as sex training by cancer professionals, patient education, and integrated survivorship programs could enhance the quality of life of these patients. Sexual dysfunction is a prevalent and impactful issue among breast cancer survivors undergoing ET.

Introduction

Breast cancer is the leading cancer among women worldwide, with approximately 2.3 million new cases reported in 2020¹. A significant proportion (approximately 70%) of patients with non-metastatic breast cancer have estrogen receptor-positive (ER+) tumors, making endocrine based therapy a standard of care in this group. Cancers that express estrogen and/or progesterone receptors can be effectively treated with endocrine therapies, such as tamoxifen or aromatase inhibitors (AI). Adjuvant endocrine therapy (ET) for a minimum of 5 years is the cornerstone of systemic treatment, delivering substantial benefits including a 50% reduction in recurrence and one-third reduction in mortality^2,3.

Although adjuvant endocrine therapy with tamoxifen or AI significantly reduces recurrence and improves the overall survival rates in patients with ER + breast cancer, it is not without side effects. Common adverse effects include hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, bone density loss, depression, cognitive dysfunction, and fatigue⁴. Among breast cancer survivors, sexual complaints were particularly prevalent, with decreased libido or sexual desire disorder (reported by 23%–64% of patients), arousal and lubrication issues (20%–48%), orgasmic difficulties (16%–36%), and dyspareunia (25%–38%)⁵.

The World Health Organization defines sexual health as a state of physical, emotional, mental, and social wellbeing in relation to sexuality⁶. Both physiological and psychosocial factors influence female sexual function. Sexual dysfunction is characterized by disturbances in sexual desire and psychological and physiological changes involved in sexual response. A woman is diagnosed with sexual dysfunction if she experiences persistent symptoms that cause marked distress for at least 6 months, as detailed in the Diagnostic and Statistical Manual of Mental Disorders, fifth Edition (DSM-5). Sexual dysfunction can affect women with and without cancer⁷. A recent review indicated that the prevalence of sexual dysfunction among women without cancer ranged 20%–40% compared to 40%–60% among women with a history of breast cancer⁷. A population-based cohort study involving 19,709 breast cancer survivors diagnosed between 1997 and 2017 compared them to 93,389 cancer-free women and found that breast cancer survivors had a higher risk of sexual dysfunction (9.1% versus 6.9%, HR 1.60, 95% confidence interval [CI] 1.51–1.70) compared to the general population⁸. The French general epidemiological cohort CONSTANCES found that 34% of their cohort had pain during sexual intercourse and 30% were not satisfied with their sex life⁹.

This multicenter study represents one of the largest national efforts to assess sexual dysfunction among Brazilian women with non-metastatic estrogen receptor–positive breast cancer undergoing adjuvant endocrine therapy, contributing relevant national data to an area that remains underrepresented in the Brazilian literature.

In Brazil, comprehensive data on sexual dysfunction in patients with breast cancer are lacking. This study aimed to determine the frequency of sexual dysfunction in women with non-metastatic ER + invasive breast carcinoma receiving adjuvant endocrine therapy and to explore its association with clinical, social, and demographic characteristics.

Methods

Study design and participants

This is a cross-sectional, observational study. Women with a history of non-metastatic ER+ (estrogen receptor level of > 1%), HER2-negative or -positive, stage I–III invasive carcinoma of the breast; who had undergone locoregional and systemic treatment according to the standards of each institution and were on active adjuvant ET with either an AI (letrozole, anastrozole, exemestane) or tamoxifen, with or without ovarian function suppression for at least 6 months and no more than 120 months; aged ≥ 18 years; and with an Eastern Cooperative Oncology Group performance status score of 0, 1, or 2 were enrolled. Conversely, individuals with a history of other malignant tumors, previous breast cancer or metachronous breast cancer, and distant metastases were excluded. The choice of ET was at the discretion of the attending oncologist, with no predefined criteria based on menopausal status, given the observational design of the study.

The following data were collected from medical records: patient demographics, medical history, histology, tumor staging and grading, hormonal receptor status, HER2 status, germline mutational status, and primary oncological treatment. Demographic variables included age, race/ethnicity, marital status, menopausal status, employment status, educational level (completion of high school or not), presence of comorbidities (e.g., diabetes, hypertension, dyslipidemia, hypothyroidism, osteoporosis, depression, and anxiety), and use of concurrent medications (including anticoagulants, antidepressants, antihypertensives, antihyperglycemics, antilipidemics, benzodiazepines, hormone-containing vaginal creams, hypnotics, thyroid hormone, and oxybutynin). Patients were stratified according to the duration of ET (< 2 years, 2–5 years, and > 5 years), age (< 40, 40–60, and > 60 years), and treatment setting (public hospital and non-healthcare insured or private hospital and healthcare-insured). A patient-reported outcome questionnaire was administered to each participant.

The study was conducted under the auspices of the Grupo Brasileiro de Estudos em Câncer de Mama (GBECAM). Ethical approval was obtained from the research ethics committee of each participating site, and Institutional Review Board approval was obtained from the coordinating center Hospital Sirio Libanês (DF) (CEP N° HSL 2020-58, CAAE 31294920.6.0000.5461, Plataforma Brasil: 4.020.472). All participants signed a written informed consent form before inclusion in the study. All research was performed in accordance with relevant guidelines and regulations.

Patient-reported outcomes

Sexual dysfunction

The validated Portuguese version of the Female Sexual Function Index (FSFI) was used to assess sexual function and dysfunction in the participants. The FSFI is a self-administered questionnaire designed to evaluate female sexual responses regarding sexual desire, sexual arousal, vaginal lubrication, orgasm, sexual satisfaction, and pain/discomfort¹⁰. The instrument consists of 19 items regarding five domains of sexual response: desire and subjective stimulation, lubrication, orgasm, satisfaction, and pain or discomfort. Each domain score was calculated by summing and then multiplying by a domain-specific factor (0.6 for desire, 0.3 for arousal, 0.3 for lubrication, 0.4 for orgasm, 0.4 for satisfaction, and 0.4 for pain) to standardize the scores across the domains. The final FSFI score, ranging from a minimum of 2 to a maximum of 36, was obtained by summing the weighted scores for each domain, with a cut-off score of 26.5 or less indicating sexual dysfunction.

Adherence

Adherence to adjuvant ET was assessed using the Portuguese version of the Morisky Medication Adherence Scale-8 (MMAS-8), an eight-item self-reported adherence scale¹¹. In this study, patients were classified as fully adherent (MMAS-8 score of 8) or with suboptimal adherence (MMAS-8 score < 8) to identify factors associated with complete adherence^12,13.

Health-related quality of life (QOL)

Health-related QOL was evaluated using validated Brazilian and Portuguese versions of the EORTC Core Quality of Life questionnaire- C30 (EORTC QLQ-C30) and EORTC Core Quality of Life questionnaire- BR-23 (EORTC QLQ BR23) instruments¹⁴. High scores for global health and functioning indicated better functioning, whereas high scores for symptoms indicated worse symptomatology.

Statistical analysis

All patients were recruited using convenience sampling after their appointment at the oncology health service. Poisson regression with robust variance was applied to estimate prevalence ratios for sexual dysfunction and its associated factors in this cross-sectional analysis. Predictive factors considered for sexual dysfunction included the type of hospital (healthcare insurance), age, ethnicity, type of endocrine therapy, duration of treatment, adherence, education level, EORTC QLQ-C30 sexual functioning score, and EORTC QLQ-BR23 breast symptom score.

Statistical analysis was conducted in two stages, bivariate and multivariate. The prevalence ratios and their respective 95% CIs were calculated for both stages. First, simple Poisson regression models were applied to each variable. Variables with p < 0.05 in the univariate analysis were entered into the multivariate model. Only variables that remained statistically significant (p < 0.05) were retained in the final model. Prevalence ratios (PRs) and 95% CIs were then calculated. Missing data, when present, were handled by a complete-case approach in the regression models. Multicollinearity between covariates was evaluated using variance inflation factor (VIF) and tolerance statistics.

All statistical analyses were performed using the SAS software version 9.4 Vienna, Austria. P values < 0.05 were considered statistically significant. Data were collected using the REDCap Electronic Data Capture (EDC) system customized for this research project¹⁵.

Results

From June 2021 to March 2024, 774 patients with nonmetastatic ER + breast cancer from 14 public and private healthcare institutions across all five regions of Brazil were included in this analysis. The median tumor size was 23.1 mm (± 17.9 mm), with a median duration of ET of 3.2 years (range: 6 months to 9.6 years). The median age of participants was 53 years (± 10.46). In the cohort, 427 patients (55.2%) had healthcare insurance (treated in private hospitals), 455 (59.2%) lived with a partner, 478 (61.9%) were postmenopausal, and 191 (24.7%) were older than 65 years. The ethnic backgrounds included 345 (45.7%) non-white patients. Regarding disease staging, 267 (34.5%), 335 (43.3%), and 172 (22.2%) patients had stage I, II, and III disease, respectively. Surgical history revealed that 467 patients (61%) underwent lumpectomy and 243 (32%) underwent axillary lymph node dissection. Prior treatment included neoadjuvant chemotherapy in 516 patients (66.9%) and radiotherapy in 642 patients (83.3%). Among these patients, 353 (45.8%) received AI, 324 (42%) received tamoxifen, and 94 (12.2%) received ovarian function suppression therapy in combination with ET. In addition, 480 (62%) patients had comorbidities. Patient baseline characteristics and treatment details are summarized in Table 1.

Table 1.

Patient characteristics at baseline and treatment details.

	Sexual Dysfunction Status (N = 346)					Overall Cohort
	Yes		No
Characteristic	n	%	n	%		n	%*
Total No. of participants	-	-	-	-	−	774	100
Sexual intercourse in the previous 4 weeks	276	79.8	70	20.2	p-value #	346	44.8
Healthcare insurance					0.52
Yes	126	81.3	29	18.7		347	44.8
No	150	78.5	41	21.5		427	55.2
Age					0.34
≤ 65 years	241	79	64	21		583	75.3
> 65 years	35	85.4	6	14.6		191	24.7
Menopausal status					0.46
Premenopause	124	78	35	22		294	38.1
Postmenopause	151	81.2	35	18.8		478	61.9
Ethnicity					0.27
White	146	81.6	33	18.4		409	54.2
Non-white	122	76.7	37	23.3		345	45.8
Marital Status					0.14
Living alone	34	72.3	13	27.6		313	40.8
Living with a partner/family	241	81.4	55	18.6		455	59.2
Education Level					0.26
Low	63	84	12	16		195	26.8
High	196	78.1	55	21.9		533	73.2
Comorbidities					0.35
Yes	121	77.5	35	22.4		294	38
No	155	81.6	35	18.4		480	62
Clinical Stage					0.65
I	95	77.9	27	22.1		267	34.5
II	115	82.1	25	17.9		335	43.3
III	66	78.6	18	21.4		172	22.2
ECOG PS					0.04
PS 0	260	78.8	70	21.2		702	90.7
PS 1	16	100	0	0		72	9.3
Type of surgery					0.77
Modified radical mastectomy	95	79.2	25	20.8		258	33.7
Adenomastectomy	18	85.7	3	14.3		41	5.3
Lumpectomy	160	79.2	42	20.8		467	60.9
Tumoral Grade					0.19
Grade 1	42	76.4	13	23.6		128	19.6
Grade 2	151	83.9	29	16.1		398	61
Grade 3	44	74.6	15	25.4		126	19.4
Axillary dissection					0.15
No	187	81.6	42	18.3		516	68
Yes	84	75	28	25		243	32
Prior CT					0.82
Yes	75	78.9	20	21		255	33.1
No	200	80	50	20		516	66.9
CT Intention					0.76
Neo-adjuvant	79	79	21	21		205	39.9
Adjuvant	120	80.5	29	19.4		309	60.1
Anti-HER2 blockade					0.34
No	232	78.9	62	21.1		661	85.5
Yes	44	84.6	8	15.4		112	14.5
Endocrine therapy					0.02
Tamoxifen	133	75.1	44	24.9		324	42
Aromatase inhibitor	97	88.2	13	11.8		353	45.8
ET + OFS	45	77.6	13	22.4		94	12.2
Duration of ET					0.33
< 2 years	86	76.8	26	23.2		261	33.8
2 to 5 years	141	83	29	17		371	48
> 5 years	48	76.2	15	23.8		141	18.2
CDK4/6 inhibitors					0.42
No	269	80	67	20		754	97.4
Yes	7	70	3	30		20	2.6
Prior radiotherapy					0.09
No	55	87.3	8	12.7		129	16.7
Yes	220	78	62	22		642	83.3
Concomitant medication					0.03
No	137	84.6	25	15.4		426	55
Yes	139	75.5	45	24.5		348	45

ECOG PS, Eastern Cooperative Oncology Group performance status scale; CT, chemotherapy; HER2, human epidermal growth factor receptor 2; ET, endocrine therapy; OFS, ovarian function suppression; CDK4/6, Cyclin-dependent kinase (CDK) 4/6.

* Total < 100% due to the evaluation of sexual dysfunction in only 346 patients from the overall cohort of 774 patients (only patients with sexual activity in the previous four weeks were included).

Of the 774 patients evaluated, 577 (74.8%) reported having an active sex life before their cancer diagnosis, and 346 (44.8%) engaged in sexual intercourse in the 4 weeks prior to the study and were thus included in the analysis. Among these, 276 patients (79.8%) exhibited sexual dysfunction according to the FSFI. Table 2 outlines FSFI domains and results for patients with and without sexual dysfunction. Patients with sexual dysfunction had significantly lower scores across all six FSFI domains, including desire, arousal, lubrication, orgasm, satisfaction, and pain.

Table 2.

Domains of the FSFI and results in patients with and without sexual dysfunction.

	Sexual Dysfunction		Overall Cohort
Domain	Yes (N = 276)	No (N = 70)	N = 346
Desire	2.48 ± 1.1	4.52 ± 0.9	2.9 ± 1.3
Arousal	2.94 ± 1.2	5.04 ± 0.6	3.37 ± 1.4
Lubrication	3.17 ± 1.4	5.46 ± 0.7	3.64 ± 1.6
Orgasm	3.34 ± 1.5	5.39 ± 0.6	3.76 ± 1.5
Satisfaction	3.85 ± 1.4	5.66 ± 0.5	4.23 ± 1.5
Pain	3.28 ± 0.9	3.07 ± 0.6	3.24 ± 0.8
Total	18.75 ± 5.2	29.00 ± 1.7	20.83 ± 6.3

FSFI = Female Sexual Function Index.

The average median age of patients with sexual dysfunction was significantly higher than that of those without (53 ± 10.4 vs. 48 ± 9.4 p = 0.0002). A significant association was observed between sexual dysfunction and Eastern Cooperative Oncology Group performance status scale (ECOG PS) (p = 0.05); notably, all 16 patients (100%) with PS1 reported sexual dysfunction. Furthermore, there was a significant association between sexual dysfunction and the type of ET (p = 0.02). Sexual dysfunction was more frequently associated with AI (88.2% of patients with sexual dysfunction) than with tamoxifen (75.1%), and ovarian function suppression was more frequently associated with ET (77.6%). Patients who did not use concurrent medications were more frequently associated with sexual dysfunction than patients that used medications (84.6% vs. 75.5%, p = 0.03). No significant influences on sexual dysfunction were found regarding the duration of ET, healthcare insurance, living arrangements, ethnicity, menopausal status, education level, disease stage, type of surgery, axillary surgery, prior chemotherapy, prior radiotherapy, or the presence of comorbidities. Table 3 presents the results of the univariate analysis of sexual dysfunction in relation to adherence to ET and QOL.

Table 3.

Univariate analysis of sexual dysfunction vs. adherence to ET and quality of life.

Characteristic	Sexual dysfunction	Absence of sexual dysfunction	p-value	Overall Cohort
	N = 276	N = 70		N = 774	%
MMAS-8 score of adherence to ET			0.33
< 8 (non-adherent to ET)	112 (77.2%)	33 (22.7%)		313	40.6
= 8 (adherent to ET)	163 (81.5%)	37 (18.5%)		458	59.4
QLQ C30 - Global health status	76.70 ± 22.5	84.40 ± 18.2	0.008	78.07 ± 22.6	-
QLQ C30 - Physical Functioning	83.12 ± 17.8	86.74 ± 15.5	0.13	82.60 ± 18.7	-
QLQ C30 - Role Functioning	80.13 ± 28.5	85.95 ± 26.2	0.07	80.47 ± 29.0	-
QLQ C30 – Emotional Functioning	60.07 ± 31.5	66.79 ± 31.9	0.06	63.48 ± 31.3	-
QLQ C30 - Cognitive Functioning	60.87 ± 31.9	68.33 ± 30.2	0.07	65.22 ± 31.5	-
QLQ C30 - Social Functioning	86.05 ± 25.6	92.62 ± 16.7	0.04	87.09 ± 24.7	-
QLQ C30 - Fatigue	25.99 ± 26.2	20.48 ± 25.2	0.06	23.80 ± 26.3	-
QLQ C30 - Nausea Vomiting	7.37 ± 14.5	8.57 ± 16.7	0.89	6.77 ± 14.5	-
QLQ C30 - Pain	29.95 ± 32.2	21.43 ± 25.5	0.09	26.17 ± 30.4	-
QLQ C30 - Dyspnea	9.42 ± 21.4	8.10 ± 20.0	0.60	9.66 ± 22.3	-
QLQ C30 - Sleeping Disturbances	37.33 ± 37.6	34.76 ± 39.1	0.50	35.29 ± 38.7	-
QLQ C30 - Appetite Loss	9.09 ± 23.3	11.90 ± 25.4	0.28	9.62 ± 22.3	-
QLQ C30 - Constipation	25.45 ± 35.1	25.71 ± 33.6	0.78	22.22 ± 32.9	-
QLQ C30 - Diarrhea	7.61 ± 21.7	3.33 ± 10.1	0.33	5.83 ± 18.0	-
QLQ C30 - Financial difficulties	19.39 ± 33.3	16.19 ± 31.5	0.46	18.68 ± 32.2	-
QLQ BR23 - Systemic Therapy Side Effects	24.17 ± 17.8	18.87 ± 17.4	0.008	21.72 ± 17.1	-
QLQ BR23 - Upset by Hair Loss	37.74 ± 37.2	29.17 ± 35.8	0.29	33.04 ± 35.4	-
QLQ BR23 - Arm Symptoms	22.71 ± 25.6	19.59 ± 23.6	0.39	21.65 ± 24.4	-
QLQ BR23 - Breast Symptoms	17.48 ± 20.9	15.69 ± 16.2	0.91	17.31 ± 20.8	-
QLQ BR23 - Body Image	75.06 ± 26.3	85.29 ± 19.5	0.003	78.82 ± 25.8	-
QLQ BR23 - Future Perspective	46.79 ± 36.3	54.90 ± 33.9	0.10	51.83 ± 35.9	-
QLQ BR23 - Sexual Functioning	30.82 ± 16.8	52.94 ± 28.0	< 0.0001	20.58 ± 22.4	-
QLQ BR23 - Sexual Enjoyment	41.59 ± 26.5	71.04 ± 23.1	< 0.0001	46.27 ± 27.8	-

MMAS-8, Morisky Medication Adherence Scale-8; ET, endocrine therapy; QLQ-C30, European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire; QLQ-BR23, EORTC QLQ specific module for breast cancer.

Patients with sexual dysfunction demonstrated significantly lower mean scores on the EORTC QLQ C30 for global health status, social functioning, body image, sexual functioning, and sexual enjoyment than those without sexual dysfunction (p = 0.008, p = 0.04, p = 0.003, p < 0.0001, and p < 0.0001, respectively). Additionally, those with sexual dysfunction had a significantly higher mean score of EORTC QLQ-BR23 systemic therapy side effects than those without sexual dysfunction (p = 0.008). Regarding adherence to ET, no differences were observed between women who adhered or not and those with sexual dysfunction (low adherence: 77.2% vs. high adherence: 81.5%, p = 0.33).

Poisson regression analysis with robust variance was performed to identify the factors associated with sexual dysfunction in patients with cancer¹⁶. The type of ET, education level and EORTC QLQ BR-23 sexual functioning (SEF) score maintained a significant association with the occurrence of sexual dysfunction (p < 0.05). Specifically, patients treated with AI exhibited a 13% higher prevalence of sexual dysfunction than those treated with tamoxifen (PR = 1.13, 95% CI: 1.01–1.26, p = 0.04). No significant differences in the prevalence of sexual dysfunction were observed between patients treated with tamoxifen and those receiving ovarian suppression plus endocrine therapy (PR = 1.0, 95% CI: 0.83–1.21, p = 0.97). Patients with higher education level exhibited a 14% higher prevalence of sexual dysfunction than those with a lower level of education (PR = 1.14, 95% CI: 1.02–1.27, p = 0.018). Furthermore, a 1% increase in the EORTC QLQ BR-23 SEF was associated with a 1% decrease in the prevalence of sexual dysfunction (PR = 0.99, 95% CI:0.98–1.0, p < 0.0001). Table 4 presents the results of multivariate analysis.

Table 4.

Multivariate analysis of sexual dysfunction.

	Prevalence Ratio Adjusted
Characteristic	PR (IC 95%)	p-value
Type of ET		0.0474
AI	1.13 (1.00; 1.26)	0.0435
Tamoxifen	1	-
ET + OFS	1.00 (0.83; 1.21)	0.9701
Education Level		0.0183
Low	1	-
High	1.14 (1.02; 1.27)	0.0183
EORTC QLQ BR-23 SEF	0.99 (0.98; 1.00)	< 0.0001

ET: endocrine therapy, PR: Prevalence Ratio, AI: aromatase inhibitors, OFS: ovarian function suppression, EORTC QLQ BR-23 SEF: EORTC Core Quality of Life questionnaire- BR-23 sexual functioning score.

Comorbidities, concomitant medications, adherence to endocrine therapy (MMAS-8), race/ethnicity, employment status, marital status, and menopausal status were evaluated in univariate analyses but were not retained in the final multivariate model. Their descriptive distributions are presented in the baseline characteristics and univariate tables.

Discussion

This study represents one of the largest multicenter analyses of sexual dysfunction among Brazilian women receiving adjuvant endocrine therapy for non-metastatic ER + breast cancer. By including patients from public and private institutions across different regions of the country, our findings provide robust national data and contribute to the clinical understanding of sexual health among Brazilian breast cancer survivors. In our cohort, about 25% of women declared themselves as sexually inactive, a lower proportion than the 40% of sexually inactive women observed in the French CANTO cohort, which included 7,985 patients¹⁷.

In our study, 276 of 346 sexually active patients (79.8%) experienced sexual dysfunction, measured using the FSFI. This indicates a higher level of sexual dysfunction among Brazilian women with ER + non-metastatic breast cancer undergoing adjuvant ET compared with previous reports on the Brazilian population. For instance, Abdo et al. found that 49% of 1,219 women in the community (without a cancer diagnosis) reported sexual dysfunction using a 38-question self-applicable questionnaire¹⁸. Similarly, Pegorare et al. reported a sexual dysfunction rate of 61.1% in a cohort of 36 women who underwent breast cancer surgery¹⁹. The discrepancies in the findings may be attributed to our study focusing solely on women treated for breast cancer, whereas Abdo et al. included the general population. Additionally, our larger sample size (774 patients vs. 36 patients in the Pegorare cohort) enhanced the reliability of our findings.

The high prevalence of sexual dysfunction, with rates approaching 80%, represents a substantial and still underrecognized burden among breast cancer survivors undergoing adjuvant endocrine therapy. These findings highlight the importance of routine and structured sexual health assessment during oncology follow-up, early symptom recognition, and integration of sexual health into survivorship care planning. Given the profound impact of sexual dysfunction on quality of life, overlooking this domain may compromise truly comprehensive and patient-centered cancer care.

The prevalence of sexual dysfunction among breast cancer survivors varies widely in the literature. A systematic review published in 2022 analyzed 5,483 women across 24 studies and reported a sexual dysfunction prevalence of 66% (95% CI: 59–74%) measured using the FSFI¹⁹. Notably, the highest rates were found in Africa (75%; 95% CI: 66%–83%), whereas the lowest rates were found in Europe (43%; 95% CI: 26%–60%)²⁰. In addition, a population-based cohort found that 65% of women with a recent breast cancer diagnosis were sexually active, with 53% experiencing sexual health issues²⁰. In contrast, our study revealed a significantly higher prevalence of sexual dysfunction (79.8%), highlighting the urgent need for targeted interventions in this population.

In a previous systematic review of 34 studies on sexual health, 31 methods were used to assess sexual function. The most commonly used instruments were the FSFI, used in four studies, and the Cancer Rehabilitation Evaluation System, used in three studies²¹. For our analysis, we selected the FSFI, a 19-item self-report questionnaire that evaluates various aspects of female sexual function including desire, arousal, orgasm, pain, and satisfaction²². Although the FSFI is a well-validated instrument for the assessment of sexual function, it has some limitations²³. The instrument evaluates symptoms over the previous four weeks and does not assess distress, which is required for a formal diagnosis of sexual dysfunction according to DSM-5 and ICD criteria. In addition, the FSFI requires recent sexual activity for full scoring, which restricted the analysis to women who had engaged in sexual intercourse in the previous four weeks. Aligning the chosen assessment tool with established criteria is essential for diagnosing sexual dysfunction. A systematic review and meta-analysis assessing sexual dysfunction in women with cancer found a mean FSFI score of 19.58 (95% CI: 17.64–21.53) for patients with breast cancer, which is lower than the mean score of 20.83 ± 6.3 observed in our cohort. Both studies indicated the presence of sexual dysfunction, defined as a score < 26.5²⁴.

Female sexual dysfunction (FSD) is primarily classified into three types: (1) female sexual interest/arousal, (2) female orgasmic pain, and (3) genitopelvic pain/penetration disorders. To qualify for a diagnosis, symptoms must persist for at least 6 months and result in clinically significant distress²⁵. Currently, there is no gold standard for evaluating all aspects of sexual dysfunction, as outlined in the DSM-5 and ICD-10²⁰. Among the components of the FSFI, only the desire domain has a validated clinical cutoff score. A score of 5 or less in this domain indicates a potential diagnosis of hypoactive sexual desire disorder (HSDD)²⁶. Our study revealed that women with and without sexual dysfunction scored below 5, indicating HSDD across both groups. Of the 346 women evaluated, 59% reported a low sexual desire frequency and 53% indicated an overall low sexual desire. A literature review of 37 studies on sexual dysfunction in patients with breast cancer found that up to 87% of patients may experience low desire, underscoring the need for targeted interventions²⁷.

The FSFI also assesses the second phase of the sexual response, which includes “excitation” and “lubrication.” This phase encompasses physiological and subjective arousal and is characterized by vaginal engorgement and lubrication²⁶. Our findings showed that participants with sexual dysfunction scored lower in the arousal domain compared to those without dysfunction (2.94 ± 1.24 vs. 5.04 ± 0.62, p < 0.0001). In terms of lubrication, 43.7% of participants reported low or absent sexual arousal, whereas 26.3% reported difficulty in achieving vaginal lubrication. Additionally, 47% experienced a low lubrication frequency and 48% had difficulty maintaining lubrication during intercourse¹⁹.

The final phase of the sexual response includes relaxation and subjective well-being; alterations in this phase can result in pelvic pain and vaginismus. Our questionnaire indicated that 29% of the participants experienced discomfort during penetration. The orgasm domain of the FSFI, which assesses the frequency and satisfaction of orgasms, revealed that 39% of patients reported low orgasm frequency, with 20.1% never or rarely reaching orgasm. Women with sexual dysfunction again scored lower in the arousal domain (3.34 ± 1.48 vs. 5.39 ± 0.63, p < 0.0001). The satisfaction domain evaluated general sexual relationship satisfaction, whereas the pain domain assessed the pain experienced during or after vaginal penetration. Notably, both groups exhibited low scores in the pain domain (3.28 ± 0.94 vs. 3.07 ± 0.57, p = 0.0012), indicating a prevalent concern across the cohort¹⁹.

Classical factors and mechanisms associated with sexual dysfunction and breast cancer have been reported in the literature, including locoregional treatments (surgery and radiotherapy) and systemic treatments (prior chemotherapy and endocrine therapy)²⁸. Surgery can lead to anatomical changes in the breast, body image disruption, scarring, pain, and alterations in sensitivity. In a series of 226 patients treated with breast-conserving surgery (n = 119), unilateral mastectomy (n = 40), and contralateral prophylactic mastectomy (n = 67), FSFI was evaluated preoperatively and after a median of 13 months postoperatively, and patients who underwent mastectomy did not exhibit superior sexual function compared to those who underwent breast-conserving surgery²⁹. In the current study, there was no difference in sexual dysfunction between patients who underwent mastectomy or breast-conserving surgery³⁰. Raggio et al. evaluated 83 breast cancer survivors using the FSFI, and over three-quarters of all participants (77%) qualified for sexual dysfunction, and mastectomy was a predictor of sexual morbidity³¹. The results presented here did not show an influence of surgery type on sexual dysfunction (p = 0.77).

Radiotherapy can cause skin lesions, tissue discomfort, alterations in sensitivity, and pain. The literature regarding the effects of radiotherapy on sexual function in patients with breast cancer has yielded conflicting results. In a systematic review of 32 studies with 5033 patients, 10 studies evaluated breast cancer patients and six reported a relationship with sex issues³². Lower body image perception and sexual and psychosocial well-being are related in patients treated with radiotherapy³². In our study, prior radiotherapy was not associated with sexual dysfunction (p = 0.09).

Chemotherapy can lead to fatigue, asthenia, alopecia, ovarian failure, and decreased libido. Endocrine therapy can cause vaginal dryness, penetration pain, vulvovaginal atrophy, and decreased libido. Chemotherapy-induced premature ovarian failure can decrease estrogen levels and cause vaginal dryness and dyspareunia²⁹. Interestingly, in our study, patients who had previously undergone chemotherapy did not experience more sexual dysfunction than those who had not (p = 0.82).

Adjuvant endocrine therapy with tamoxifen or aromatase inhibitors can lead to sexual side effects, even in women who are already in menopause³³. A cross-sectional survey using FSFI questionnaires mailed to 296 breast cancer patients in the first 2 years of AI therapy was completed, and 93% of the participants scored as having sexual dysfunction³⁴. In our study, AIs were associated with sexual dysfunction (p = 0.02). In the multivariate analysis, the type of ET and QLQ BR23 - SEF showed a significant association with the occurrence of sexual dysfunction (p < 0.05). In a population-based study conducted among postmenopausal breast cancer patients, 42.4% of patients receiving AI were generally dissatisfied with their sex life, which was significantly more common than in patients receiving tamoxifen (p < 0.05)³⁵. Our study also found that sexual dysfunction was more frequently associated with AI use (88.2% of those with sexual dysfunction) than with tamoxifen use (75.1%).

Although healthcare insurance status was not independently associated with sexual dysfunction in our cohort, this variable remains clinically relevant as a surrogate of socioeconomic status. Access to specialized sexual health care, psychological support, and survivorship programs may differ substantially between public and private healthcare systems in Brazil.

Up to 70% of women diagnosed with breast cancer have comorbidities in addition to cancer. In a French study of 235,368 women with early breast cancer, 47% of patients had at least one comorbidity, which was higher than the 38% of women with breast cancer and comorbidities in the present survey³⁶. In a retrospective study of 90 Brazilian patients with breast cancer, the presence of comorbidities increased the risk of sexual dysfunction by 2.5 times (OR: 2.5, CI: 1.2–4.9, p = 0.009)³⁷. In our analysis of sexual dysfunction, 184 patients used concurrent medications, whereas 162 did not. Additionally, 190 patients had comorbidities and 156 did not. Notably, although the presence of comorbidities did not correlate with sexual dysfunction in our cohort, 16 patients with an ECOG performance status of 1 reported experiencing sexual dysfunction. However, the limited sample size prevented definitive conclusions. An intriguing relationship was identified between the absence of concurrent medication use and sexual dysfunction, with a statistically significant p value of 0.03. This finding suggests that medication management may play a role in the sexual health of the patients in this cohort. (p = 0.03).

Patients with sexual dysfunction had poorer global health status, social functioning, body image, sexual functioning and sexual enjoyment and systemic therapy side effects scores than those without sexual dysfunction (p = 0.008, p = 0.04, p = 0.003, p < 0.0001, p < 0.0001, and p = 0.008, respectively). These results showed that patients with sexual dysfunction could have considerable impairment in several QOL domains. A French prospective study among 7895 patients with breast cancer observed that poor body image was the most common sexual concern, being reported by over 50% of patients 2 years after diagnosis, particularly patients who received more intense treatment, including more extensive surgery, chemotherapy, or ET¹⁷. Both sexual functioning and sexual enjoyment EORTC BR23 (20.58 ± 22.4 and 46.27 ± 27.8, respectively) have low values compared with other domains, such as body image and future perspectives, in the overall cohort (78.82 ± 25.85 and 51.83 ± 35.9, respectively) in our study. Low values of sexual functioning may indicate difficulties or loss of interest, often associated with the side effects of treatment or physical changes. The EORTC BR23 sexual functioning score is very low, and a score of 78.82 for body image may reveal that sexual issues are not related to body perceptions. These results of low EORTC BR23 scores for sexual function correspond with the result of the FSFI questionnaire scores of 20.83 ± 6.3 in the overall population (indicative of sexual dysfunction), both indicating sexual health problems.

While several variables showed significant associations with sexual dysfunction in the univariate analysis, only a subset of these remained significant in the multivariate model. Specifically, the multivariate analysis confirmed that the use of aromatase inhibitors, higher educational level, and lower EORTC QLQ BR-23 sexual functioning scores were independently associated with increased prevalence of sexual dysfunction. For instance, although ECOG status showed a significant relationship in univariate analysis, this effect was not sustained after multivariate adjustment, suggesting potential confounding by age or comorbidities to influence global health status and sexual dysfunction. The independent effect of AI use on sexual dysfunction aligns with previous reports and underscores the need for tailored sexual health support in this group³⁴. The association between higher education level and increased prevalence of sexual dysfunction may reflect greater symptom awareness, improved health literacy, and a higher likelihood of reporting intimate symptoms, rather than a true biological increase in dysfunction. These findings reinforce the value of multivariate modeling in distinguishing true predictors from artifacts of bivariate associations.

This study had some limitations. Although we enrolled patients from 15 healthcare institutions, the number of patients varied, which could compromise the generalizability of the results. The absence of a distress assessment and prospective evaluation for at least 6 months precludes a true diagnosis of sexual dysfunction, as diagnostic criteria require sexual complaints to be associated with significant amounts of distress for a minimum of 6 months. It is also be noted that a clinical diagnosis of sexual dysfunction cannot be made without ruling out other medical conditions or medications that can affect sexual functioning. The conclusions about the relationship between sexual dysfunction and age are less than robust, as few patients under 40 years of age were enrolled. Although there was no difference in the rates of sexual dysfunction among the different intervals of ET from 6 months to 2 years, 2–5 years and > 5 years, the analysis of duration of ET and sexual dysfunction could be compromised, as this was a cross-sectional study, and the data about patients who began adjuvant ET and quit as well as the reasons for quitting are not known. We did not evaluate mental health and family support in relation to sexual function, which could have affected the results. Although the FSFI does not provide insights into the degree and type of sexual dysfunction experienced, it can be used to guide further assessments within the spectrum of sexual dysfunction diagnoses.

Despite the prevalence of sexual dysfunction symptoms in most women with and without cancer, this health domain is often neglected in usual care, and a minority of patients receive information and education on sexual function. The healthcare team may not be comfortable with the discussion or may not have the background or knowledge to discuss the subject with patients. One strategy that can be implemented is training the team on the PLISSIT (permission, limited information, specific suggestions, and intensive therapy) model or BETTER (bring up, explain, tell, time, education, record) model that can help with approaching sexual health discussions regarding sex issues^38,39. In the PLISSIT model, the first level in meeting the sexual health needs of the individual is the evaluation process. In the second level, where information is provided about the effect of the disease on sexuality and how treatment can affect sexual function, it is emphasized that informing patients about their treatment effects on sexual health, which has an important place among nursing interventions. The third level includes special suggestions and information for the individual/partner to make their sexual life more satisfactory. The fourth level involves intensive therapy and requires referral to a specialist in sexual rehabilitation⁴⁰. In the BETTER model, the first stage (bringing up) involves discussing the issue of sexual relations with patients. The second stage (explaining) involves counseling on the importance and impact of sexual issues on QOL. The third stage (telling) involves informing and explaining sexual problems. The fourth stage (timing) involves paying attention to scheduling. The fifth stage (education) includes educating about changes in sexual function due to cancer and its treatments as well as recognizing and correcting misconceptions. The sixth stage (recording) involves recording the important aspects of the discussions, evaluations, and interventions⁴¹. The establishment of dialogues can be addressed by healthcare professionals during routine follow-up care.

Education on aspects of sexual health can begin during medical training, especially in centers of excellence and academic institutions. Simple measures, such as the regular use of vaginal moisturizers to improve dryness, dyspareunia, and sexual satisfaction, can be implemented during follow-up appointments with good results, as shown in previous studies^21,42. A pilot study found that a 6-month supply of a vaginal moisturizer (hyaluronic acid-based or prebiotic-based) and a vaginal lubricant and dilator, plus access to an educational website and phone coaching helped women starting AI maintain stable sexual function⁴³.Establishing survivorship programs focuses on managing treatment toxicities and improving the QOL of cancer survivors and can also contribute significantly to the enhancement of sexual health. An early referral for a routine evaluation by a gynecologist and counseling with a focus on sexual complaints may also help address these issues. Sexual health must be addressed during the follow-up of patients with breast cancer. As we have shown, patients receiving AI endocrine therapy have a higher prevalence of sexual dysfunction, and these patients can be enrolled in psychological counseling and sexual health support programs.

Concrete strategies to address sexual dysfunction in this population include the routine use of validated screening tools such as the FSFI or brief sexual health questionnaires during oncology follow-up visits, early referral to gynecologists, psychologists, or sexual health specialists, and structured counseling interventions based on PLISSIT or BETTER models.

Given the similarities in access barriers, cultural aspects, and healthcare organization across several low- and middle-income countries, our findings may be generalizable beyond Brazil, particularly to other Latin American settings.

Future research should include longitudinal studies evaluating the evolution of sexual dysfunction over time and after ET. Another research field should investigate the impact of alternative or combined therapies, such as sexual rehabilitation interventions and supportive therapies, on patients undergoing endocrine therapy.

Conclusions

Sexual dysfunction is a major concern in women. One of the main reasons for assessing sexual function is that interventions can be performed to improve sexual health in women in general, especially those with a history of breast cancer. The 79.8% rate of sexual dysfunction in our study indicates that this is an urgent unmet need of our patients. Integrating sexual health approaches into oncological care is of great importance, particularly for women undergoing long-term AI treatment. Strategies such as routine evaluation by a gynecologist, training the team on the PLISSIT model, and establishing survivorship programs, could help address this issue.

Author contributions

D.A.-S. and R.A. conceived and designed the study. D.A.-S., D.L.-S., H.R., F.C.M., S.C.S.O., A.K.S., A.L.Z.G., B.S.W.S., A.G.C.C., M.C.F.M.A., Y.C.R.B.B., M.C.F.M., C.P.S., C.E.P., P.A.S., D.J.P., A.N.-R., D.D.R., and R.B.-S. contributed to data acquisition. D.A.-S. performed the statistical analysis. D.A.-S. drafted the first version of the manuscript. D.L.-S., H.R., F.C.M., S.C.S.O., A.K.S., R.A., A.L.Z.G., B.S.W.S., A.G.C.C., M.C.F.M.A., Y.C.R.B.B., M.C.F.M., C.P.S., C.E.P., P.A.S., D.J.P., A.N.-R., D.D.R., and R.B.-S. critically revised the manuscript for important intellectual content. All authors interpreted the data, reviewed the final version of the manuscript, and approved it for submission.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval

Ethical approval was obtained from the research ethics committee of each participating site, and Institutional Review Board approval was obtained from the coordinating center Hospital Sirio Libanês (DF) (CEP N° HSL 2020-58, CAAE 31294920.6.0000.5461, Plataforma Brasil: 4.020.472).

Consent to participate

All participants signed a written informed consent form before inclusion in the study.

Consent to publish

The authors affirm that human research participants provided informed consent for publication.