Sexuality is a keystone of human beings and life quality. Sexual activity is complex and usually involves physical, psychological, emotional, and hormonal status. ^{1 , 2} Limits to incorporating sexual health into comprehensive care for patients with hemophilia (PWH) include provider and patient comfort with sexual health and activity. ³ Moreover, cultural and social factors may deeply influence the comfort level of the healthcare provider and the patient discussing sexual health. ⁴ Thus, in PWH, knowledge about sexual health, difficulty with sexual activity and intimacy (sexual difficulty) is not enough explored and is extremely restricted. ^{4 , 5} Based on our personal experiences with patients in one side, and on discussions with hemophilia providers in the other side, we supposed that sexual health is insufficiently and not routinely assessed or discussed at our center. This led us to conduct, to the best of our knowledge, this first Tunisian study to investigate the specific types of sexual issues experienced in PWH and to assess factors associated with erectile dysfunction (ED).

This is an observational study performed at the regional hospital of Farhat Hached, Sousse, Tunisia. PWH registered at the local register met the following eligibility criteria, were included: aged 18 or over, and did not require special assistance to complete the questionnaire. Exclusion criteria involved PWH associated with other bleeding disorders and those who refused to answer the questionnaire. Eligible patients were invited to join the study through telephone contacts. Data were collected using the questionnaire of the International Index of Erectile Function IIEF15 in its Arabic version ^{6 , 7} and by using a clinical record created to collect clinical and sociodemographic data, via interviews and medical records search.

The IIEF 15 contains 15 items addressing the relevant domains of male sexual function that is erectile function, orgasmic function, sexual desire, and sexual satisfaction. The questionnaire is composed of five parts ⁷ : -

Erectile function (comprised of 6 questions Q1, 2, 3, 4, 5 and 15): the domain of erectile function allows this graduation of the ED: ✓

Normal: score 26-30.

The results obtained were analyzed by the SPSS (Version 26). For quantitative variables, normality was tested by the Chi squared test. The qualitative variables are expressed in counts and percentages and were tested by the t student test. The logistic regression model was conducted to establish the association between ED and variables as possible predictors. The significance level was established at <0.05.

Ethically, all the patients included gave their consent to answer the questionnaire after being informed of the objective of the study and the anonymity of the questionnaire. We preferred oral consent to written one because it was more practical and easily feasible. Moreover, as we are dealing with sexual issues, we thought that oral consent allowed us to safeguard the participant’s anonymity and to reassure participants for the anonymity of their personal information. In all cases, the research and the purposes of this research were fully described to participants. Verbal informed consent has been obtained from all participants in the study in the following way: All the participants have received written invitations, which described and specified the purpose and terms of the study. When the participants showed up on the scheduled day for the interviews and the dialogue workshop, the conditions were repeated verbally with a specific emphasis on the measures taken to ensure confidentiality and anonymity in the report/article. This study and the collection of the different interview data was approved to be in accordance with standards for good scientific practice by the Committee for Research Ethics at Farhat Hached University Hospital, Tunisia (Ref: CER: 29-2022).

We included in our study 50 eligible patients. Seven patients were excluded as they didn’t complete the questionnaire. 43 patients were finally retained and were interviewed, from June to August of 2022, representing 86% of the total. The majority (88.4%) was suffering from hemophilia A and 11.6% were suffering from hemophilia B.

In our population study, mean age was 33 years. The most important age group was 30–39 years old (41.8%). Almost half of patients were single (51.2%), not having children in 41.9% of cases, and unemployed in 55.8% of cases. Fourteen (32.6%) respondents were identified as having a severe disease, twenty (46.5%) with moderate disease and nine (20.9%) with mild disease. All patients suffered from hemophilic arthropathy but at varying stages. The most affected joint was the knee. Co-morbidities included Human immunodeficiency virus (HIV) and Hepatitis type B and Diabetes Mellitus in one patient respectively.

Table 1 illustrates socioeconomic, demographic and clinical characteristics of PWH included in our study.

In the IIEF 15 questionnaire, the general average score was 46. Table 2 shows the average scores of each domain of the IIEF-15 questionnaire. ED was observed in 93% of cases; it was severe in 20.9% of cases ( Figure 1).

Lack of desire and orgasm was observed in 76.7% of cases each. Lack of Sexual satisfaction and global satisfaction were noted in 83.7% of cases and 88.4% of cases, respectively ( Table 2).

ED was significantly associated with participants' age (p=0.034). In fact, older age was associated with ED. Neither the clinical factors nor the other sociodemographic factors (overweight, level of education, professional and marital status) were associated with ED and this is probably due to the reduced number of our patients ( Tables 3 and 4).

To the best of our knowledge, we herein report the first pilot study of various sexual difficulties using the IIEF score in PWH. IIEF 15 is a linguistically validated questionnaire that has been reproduced in l0 languages and is readily self-administered in research or clinical settings. It has a high sensitivity and specificity in treatment-related changes in patients with ED. ^{6 , 7}

Currently, data related to sexual health in PWH are lacking. Sexual difficulty in PWH is not sufficiently discussed in routine hemophilia care because of many factors including lack of awareness, understanding and resources. ⁸ In one hand, physicians may be hesitant to enquire about patient’s sexual issues and in the other hand, patients are often embarrassed to discuss about their sexual problems. ⁹ Lower levels of knowledge in the field of sexual activity among adult’s males with hemophilia were reported in a Canadian study. ¹⁰ This lack of information is also reported in the pilot study performed by Tobase et al. ¹¹ In fact, thirty percent of respondents thought they did not have satisfactory information concerning sexual activity in light of their bleeding disorder and roughly two-thirds (63%) of respondents’ desire to be informed about sexual health issues at their consultation. Based on these facts and according to our personal experiences with patients and discussions with hemophilia providers, we supposed that sexuality is also insufficiently assessed or discussed at our center. This led us to carry out this study to reveal if there is sexual health impairment in our PWH and therefore trying to improve their sexual health.

A proper understanding of the expectable sexual complications of hemophilia, the related comorbidities, and sexually related psychological issues are the essential elements required for sexual healthcare for PWH.

Tobase et al., investigating sexual health by using a 54-item patient reported questionnaire, ¹¹ demonstrated that forty percent (8 out of 20) of respondents believed that their bleeding disorder had a negative impact on their sexual life. In fact, a considerable proportion of PWH bleeds related to sexual activity. However, in this study, sexual difficulty in PWH was not detailed.

Psychosocial issues reported by patients suffering from moderate to severe hemophilia were reported in the analysis of The Hemophilia Experiences, Results and Opportunities (HERO), it was reported that a significant number of young adults with hemophilia (37%/32%) thought that this affection disturbed their ability to make close relationships with a partner or prospective partner. ⁵ The sexual difficulties were not detailed in this analysis.

Based on Germini F. et al. study, predictive factors and prevalence of sexual issues in PWH were assessed. ⁴ In this report data was analyzed from the Patient Reported Outcomes Burdens and Experiences (PROBE), which is a 29-item questionnaire dealing with patient’s health status and quality of life. ^{4 , 12} In this report, between January 2016 and February 2017, 3979 adults were enrolled from 48 countries. Sexual difficulties were found in a total of 302 PWH (15, 1%). PWH with bleeding events were 3, 82 times experiencing sexual problems. ⁴

In quality-of-life studies in PWH, erectile dysfunction and generalized sexuality were reported. ^{10 , 13} Erectile function is classified as organic, psychogenic, or mixed organic and psychogenic. ¹⁴ In most cases of ED, an organic basis is generally found, ¹⁵ typically vascular in nature, ¹⁶ but psychological factors are also frequently present. ⁴ It is crucial to differentiate organic ED from psychogenic one. Classic organic ED is associated with diminished erections in all situations. In contrast, men with classic psychogenic ED have evidence of intact erectile function in certain situations, such as with self-stimulation or occasionally upon awakening. In some cases, and in the absence of evidences of an organic or psychogenic pattern, further laboratory investigation is required. Our study demonstrated ED in 93% of cases, moderately severe, and severe in 16.30% and 20.9%, respectively. This result can be explained by the frequency of arthropathy in our patients and probably by the frequency of bleeding which unfortunately was not studied in our patients.

Several studies have tried to determine contributing factors of sexual difficulties in PWH. ^{4 , 17 , 18}

Acute and/or chronic pain has a negative impact on physical and emotional performance. Patients suffering from chronic pain have, for the most of them (73%), pain-related difficulty with sexual activity. ¹⁷ Sexual functioning is also affected by the consequences of pain management. ¹⁸

Moreover, bleeding was a great dilemma. Data found that PWH have more frequently recurrent sexual difficulties in cases of bleeding events occurring prior two weeks or having limb-threatening bleeding in the previous year. ⁸

In addition, joint pain, restriction and lack of mobility can restrict sexual intercourse and sexual position resulting in sexual difficulty. ^{19 , 20}

Comorbidities impacting sexual function were also evaluated in the study performed by Germini and al. ⁴ Hemophilia patients with underlying diseases such as viral hepatitis, HIV, diabetes Mellitus, high blood pressure and arthritis were approximately two times more likely to have sexual difficulties. In our study, because of limited number of patients (comorbidities in only 1 patient, and a positive serology for infections with contagious diseases in only 2 patients) didn’t allow us to study their correlation with different domains of IIEF 15.

Additionally, it was demonstrated that severe disease in PWH increases two times the risk of sexual problems. ⁴

Multicenter inclusion will allow investigating contributing factors of sexual difficulty.

We suppose that this pilot study provides main insights and highlights into a poorly understood aspect of our patient’s sexual health. Nonetheless, our data indicate that further studies are needed to evaluate sexual health knowledge and experience in a larger cohort of PWH, including a younger and more diverse population, to enable us to develop and provide appropriate comprehensive care for our patients.

Fortunately, PWH are living longer and healthier lives, which allows the focus of comprehensive care to address all the essential health requirements including physical, mental and sexual health. Barriers to incorporating sexual health into comprehensive care for PWH include provider and patient comfort with the topic of sexual health. Having knowledge about sexuality in PWH is important in order to inform clinicians, other healthcare providers, and stake holders involved with policy development and comprehensive hemophilia care. The ultimate goal is to improve sexual health and well-being in PWH.