Glycometabolic Control Does Not Affect Sexual Function in a Cohort of Women with Type 1 Diabetes: Results of an Observational Pilot Study

Abstract

Background/Objectives: The association between sexual dysfunction and diabetes is well known, but few studies have investigated its prevalence in type 1 diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of women with T1D, regardless of their age, and to compare its different prevalences in women treated with different insulin regimens. Methods: The population included 77 women affected by T1D, of which 16 were on Multiple Daily Injections (MDI) and 61 on Continuous Subcutaneous Insulin Infusion (45 on Advanced Hybrid Closed Loop System with catheter and 16 on patch pump). All participants completed the Female Sexual Function Index (FSFI), a questionnaire that evaluates several aspects of sexual function. Another questionnaire that evaluated general features, diabetes-specific features and sexual-specific features was proposed to every participant. Results: The overall prevalence of female sexual dysfunction was 49.3%. A correlation was demonstrated between the prevalence of female sexual dysfunction and age; another correlation was found between the prevalence of female sexual dysfunction and dyadic status. No correlation between glycemic control and sexual dysfunction was found. Conclusions: Women with T1D presented a high prevalence of sexual dysfunction, independently from glycometabolic disease control and insulin regimens; on the other hand, a significant correlation was demonstrated with age and dyadic status. Evaluation of sexual function in women with T1D appears to be important in clinical settings independently from disease control.

1. Introduction

According to the World Health Organization (WHO), sexual health encompasses physical, emotional, psychological and social well-being, emphasizing sexual desire and fulfilment, rather than solely the absence of disease, dysfunction, or disability. Sexual health is determined by the interplay of various elements, including cardiovascular, neurological and hormonal factors, associated with psychological aspects and interpersonal relationships [1]. Female sexual dysfunctions (FSD) are, on the other hand, a group of conditions that affect women of all ages and are characterized by significant disturbances in sexual response or sexual pleasure [2]. FSD are a commonly reported health problem with an estimated prevalence in the general population ranging between 30 and 70%, depending on different research methodologies and marked variation in the studied populations [3].

Diabetes, one of the world’s major public health issues, encompass a group of metabolic diseases characterized by hyperglycemia, which results from defects in insulin secretion and/or insulin action. DM can contribute to sexual dysfunction through various mechanisms, including endothelial damage, neuropathy, hormonal imbalances and psychological factors [4]. The management of type 1 diabetes (T1D) has changed substantially over the last few years. Evolving technologies offer the potential to highly improve glycemic control. Systems able to integrate insulin infusion with continuous glucose monitoring (CGM) are now widely used by patients with T1D [5]. Currently, the CGM parameters indicating a good glycemic control are defined by the International Consensus as: Time in Range (TIR) (70–180 mg/dL) > 70%, Time below Range (TBR) (<70 mg/dL) < 4%, TBR < 54 mg/dL < 1%, Time Above Range (TAR) (>180 mg/dL) < 25%, TAR > 250 mg/dL < 1% [6]. Those parameters are also supported by several real-world evidence studies [7].

It has been reported that the prevalence of FSD is higher in women with T1D—an autoimmune disease in which pancreatic beta cells are destroyed, resulting in a complete failure of insulin secretion—than in those with type 2 diabetes (T2D) or those without diabetes [8,9]. According to a recent systematic review and meta-analysis, FSD in premenopausal women are two and three times more frequent in T1D women compared to women with T2D and without diabetes, respectively [10,11]. Several factors are involved in sexual function and dysfunction in T1D: women with T1D are more likely to have been living with this disturbance during their adolescence and reproductive years; studies have also shown that autonomic neuropathy, a frequent complication in T1D, is significantly associated with FSD [12]; additional diabetes-specific factors, such as visible tissue damage related to insulin injection sites, fear of hypoglycemia during intercourse and impact of wearable diabetes technologies, like glucose sensors and insulin pumps, seem to influence the incidence of FSD [13]. Several authors have also suggested that the higher prevalence of FSD in women with T1D depends mostly on psychological aspects related to the condition and quality of life [14]. The METRO study, a single-center, longitudinal observational study aimed at the evaluation of the metabolic and endocrinological profile of young patients with T1D [15], is a milestone in the studies that have explored FSD in T1D: it demonstrated that women with T1D aged 18–35 years wearing an insulin pump exhibited a prevalence of sexual dysfunction similar to that of healthy age-matched women, although lower than that of women in treatment with Multiple Daily Injections (MDI) [14]. Another Italian study, conducted by Zamponi et al. [16] on women with T1D aged 18–45 years, demonstrated a higher prevalence of FSD in women treated with MDI compared to CSII. The above-mentioned results are in line with a previous French study, which showed that only 10% of pre- and post-menopausal women with T1D reported a negative impact of CSII on sexual life [17]. Other previous studies have evaluated the prevalence of FSD in women with T1D despite of age and menopausal status, documenting similar results in terms of high prevalence of FSD [14,18,19].

In this context, the primary aim of this study was to evaluate the prevalence of FSD in a cohort of women affected by T1D regardless of their age or menopausal status; the secondary ones were to evaluate differences on sexual function between different types of insulin therapy, including MDI and CSII with either Advanced Hybrid Closed Loop System with catheter (c-CSII) or with patch pump (pp-CSII), to assess the association between the prevalence of FSD and biochemical parameters commonly used to estimate glycometabolic control in clinical practice and to evaluate the correlation between different domains of sexual function and T1D characteristics.

2. Materials and Methods

2.1. Participants

In the present observational study, an anonymous questionnaire was proposed to women who attended the outpatient clinic of Diabetology Clinic of IRCCS Ospedale Policlinico San Martino and Diabetology Clinic of IRCCS Istituto Giannina Gaslini during the period December 2022–April 2023. The STROBE checklist was adopted for study reporting [20] and is available in Supplementary File S1. The inclusion criteria were age ≥ 18 years, diagnosis of T1D according to ADA criteria [21] for at least 6 months, insulin therapy with CSII or MDI for at least 3 months. The questionnaire was not proposed to subjects with major health problems other than complications of diabetes, including neoplasms, major depression or other psychiatric disorders, severe neurological diseases, drug or alcohol abuse.

2.2. Questionnaire and Data Collection

In women, sexual function was assessed by completing the Female Sexual Function Index (FSFI), a validated self-report questionnaire including 19 items subdivided into six domains (desire, arousal, lubrication, orgasm, satisfaction and pain) referring to sexual activity in the last 4 weeks [22]. Each domain was scored on a scale from 0 or 1 to 6, with higher scores indicating better function. For each domain, a score was calculated, and the total score was obtained by adding up the six domains’ scores. The total score range was 2–36. An alteration of sexual function was demonstrated, as largely validated, by a score of 26.55 or less on the questionnaire, of which a validated Italian version was available and utilized in the study [23]. A questionnaire that investigated personal characteristics of the subjects was associated with FSFI. The questions concerned general features like age, menopausal status, dyadic status and the use of estro-progestinics; diabetes-specific features such as type of therapy, duration of ongoing therapy and the use of continuous glucose monitoring system (CGM); sexual-specific features, including hypoglycaemic events or the tendency to remove insulin pumps during intercourse. The study was proposed to subjects who met the inclusion criteria during scheduled visits. The questionnaire was administered online and anonymously. The informed consent form already signed by patients, in which they agreed on the use of clinical data for research purposes, was used. In addition, all patients provided a specific informed consent form for the collection of data. The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice. To obtain truthful responses and give more perception of anonymity to participants, questions exploring body mass index, cigarette consumption and other factors impacting sexual functions were not included in the questionnaire [3]. For the same reason, the questionnaire provided interval responses (for example, How old are you? A. 18–25 years old; B. 26–40 years old; C. 41–60 years old; D. more than 60 years old), and therefore, it was not possible to obtain statistical findings such as mean or standard deviation for those specific features.

2.3. Statistical Methods

Descriptive statistics were generated for the whole cohort. Data are expressed as the mean and standard deviation for continuous variables and as absolute or relative frequencies for categorical variables. The distribution of the data was analysed using the Kolmogorov–Smirnov test. Non-parametric statistics were considered as appropriate. Differences between groups were evaluated using the Mann–Whitney U-test for continuous variables and the χ2 or Fisher exact test for categorical variables. A p-value of <0.05 was considered statistically significant; all P-values were based on two-tailed tests. Statistical analysis was performed using the Statistical Package for the Social Sciences for Windows (SPSS Inc., Chicago, IL, USA).

3. Results

From the 104 potential participants, 9 were excluded (4 due to psychiatric disorder, 3 due to concomitant neoplasm, 1 due to drug abuse, 1 due to neurological disease) and 18 refused to complete the questionnaire (Figure 1). Therefore, a total of 77 participants were included in the study, of which 16 were in treatment with MDI, 45 were in treatment with c-CSII and 16 were in treatment with pp-CSII.

The characteristics of the study group and the comparison of the different therapeutic regimens are shown in Supplementary Table S1. Statistically significant differences were demonstrated in terms of duration of ongoing therapy (MDI versus c-CSII and MDI versus pp-CSII, both with p < 0.01) and in terms of glycometabolic control of the disease: subjects with MDI displayed a lower frequency of TIR ≥ 50% compared with subjects in treatment with c-CSII (p = 0.02).

Table 1. FSFI domain scores, prevalence of FSD in the whole study group and comparison between different treatment groups (n = number).

	Total (n = 77)	MDI (n = 16)	c-CSII (n = 45)	pp-CSII (n = 16)
FSFI domains
Desire	3.69 ± 1.22	3.60 ± 1.10	3.73 ± 1.21	3.64 ± 1.44
Arousal	3.75 ± 2.18	4.22 ± 1.85	3.76 ± 2.24	3.26 ± 2.38
Lubrication	3.76 ± 2.32	4.27 ± 2.07	3.81 ± 2.36	3.13 ± 2.48
Orgasm	3.65 ± 2.32	4.12 ± 2.12	3.68 ± 2.37	3.10 ± 2.38
Satisfaction	4.25 ± 1.83	4.22 ± 1.55	4.40 ± 1.87	3.87 ± 2.04
Pain	3.93 ± 2.46	4.32 ± 2.00	4.11 ± 2.47	3.02 ± 2.76
FSFI total score	23.04 ± 10.95	24.77 ± 9.58	23.49 ± 11.23	20.03 ± 11.51
FSD diagnosis
Yes	38 (49.3)	8 (50)	20 (44.4)	10 (62.5)
No	39 (50.7)	8 (50)	25 (55.6)	6 (37.5)

shows the scores of the FSFI questionnaires in the different evaluable domains and the prevalence of FSD across the different therapeutic regimens’ groups. The overall prevalence of FSD was 49.3% (38/77). No statistically significant differences were observed between MDI, c-CSII and pp-CSII groups in terms of prevalence of female sexual dysfunction (50%, 44.4% and 62.5%, respectively).

Based on age ranges, as highlighted in Figure 2, a statistically significant difference was observed in the prevalence of FSD between the 18–25-year-old group and 26–40-year-old group and between the 26–40-year-old group and >60-year-old group (p = 0.03 and p = 0.01, respectively).

Evaluating different FSFI domains, as shown in

Table 2. FSFI domain scores and the prevalence of FSD in different age range groups (n = number).

	Age 18–25 Years (n = 41)	Age 26–40 Years (n = 19)	Age 41–60 Years (n = 8)	Age > 60 Years (n = 9)
FSFI domains
Desire *☐s	3.94 ± 1.24	3.73 ± 1.32	3.53 ± 0.75	2.60 ± 0.67
Arousal	3.64 ± 2.35	4.29 ± 2.03	3.53 ± 2.26	3.30 ± 1.77
Lubrication	3.45 ± 2.37	4.48 ± 2.13	3.94 ± 2.54	3.53 ± 2.34
Orgasm ☐	3.36 ± 2.45	4.51 ± 2.14	3.80 ± 2.43	3.07 ± 1.77
Satisfaction ☐	4.30 ± 1.79	4.80 ± 1.73	3.95 ± 2.12	3.16 ± 1.75
Pain	3.45 ± 2.62	4.93 ± 1.90	4.35 ± 2.72	3.60 ± 2.15
FSFI total score	22.14 ± 11.10	26.74 ± 10.57	23.09 ± 12.19	19.26 ± 9.44
FSD diagnosis ☐T
Yes	23 (56.1)	5 (26.3)	3 (37.5)	7 (77.8)
No	18 (43.9)	14 (73.7)	5 (63.5)	2 (22.2)

* p-values related to differences between the >60-year group and 18–25-year group < 0.05; ^☐ p-values related to differences between the >60-year group and 26–40-year group <0.05; ^s p-values related to differences between the >60-year group and 41–60-year group < 0.05; ^T p-values related to differences between the 26–40-year group and 18–25-year group <0.05.

, significantly lower scores in the desire domain were found in the age group over 60 years old compared with other groups (p < 0.01 vs 18-25-year-old group, p = 0.02 versus 26–40-year-old group and p = 0.02 versus 41–60-year-old group). The 26–40-year-old group also presented significantly higher scores compared to the group over 60 years old in other domains, such as orgasm (p = 0.03) and satisfaction domain (p = 0.02).

Regarding menopausal status, as shown in

Table 3. FSFI domain scores and the prevalence of FSD in subjects in menopausal status and not in menopausal status and in subjects on estro-progestinic therapy and not on estro-progestinic therapy. (n = number).

	Menopausal Status (n = 12)	No Menopausal Status (n = 65)	Use of Estro-Progestinic (n = 25)	No Use of Estro-Progestinic (n = 52)
FSFI domains
Desire *	2.85 ± 0.81	3.84 ± 1.23	3.48 ± 0.98	3.78 ± 1.32
Arousal	3.55 ± 1.60	3.79 ± 2.29	4.15 ± 1.77	3.56 ± 2.35
Lubrication	3.85 ± 2.11	3.75 ± 2.38	4.20 ± 1.95	3.55 ± 2.48
Orgasm	3.67 ± 1.80	3.65 ± 2.41	3.87 ± 2.13	3.55 ± 2.42
Satisfaction *	3.47 ± 1.65	4.40 ± 1.84	4.75 ± 1.22	4.02 ± 2.03
Pain	4.23 ± 2.14	3.87 ± 2.52	4.51 ± 1.79	3.65 ± 2.69
FSFI total score	21.62 ± 9.18	23.30 ± 11.29	24.97 ± 8.84	22.11 ± 11.80
FSD diagnosis
Yes	7 (58.3)	31 (47.7)	11 (44.0)	27 (51.9)
No	5 (41.7)	34 (52.3)	14 (56.0)	25 (48.1)

* p-values related to differences between menopausal status group and no menopausal status group < 0.05.

, no statistically significant differences were observed in terms of FSD prevalence, but a difference was present in both desire domain and satisfaction domain: the menopausal status group showed significantly lower scores in the desire and satisfaction domains compared to the no menopausal status group (p < 0.01 and p = 0.05, respectively). No statistically significant differences in terms of FSD prevalence or FSFI domains score were found between subjects who were on estro-progestinic therapy and subjects who were not.

Evaluating glycometabolic control of the disease, Figure 3 shows the differences in FSFI domains scores between the different ranges of TIR and different percentages of HbA1c, frequently used in clinical practice as suggested in latest ADA Standards of Care [24]; no statistically significant difference was observed between groups.

No statistically significant differences were demonstrated in terms of prevalence of FSD or regarding FSFI total score, as demonstrated in Figure 4.

Dividing the subjects in groups according to dyadic status, most of the FSFI domains scores were found to be significantly lower in subjects who were not in a relationship as compared to subjects who were in a relationship, regardless of the duration, as presented in Figure 5.

Also, the prevalence of FSD was significantly higher in subjects who were not in a relationship than in subjects who were in a relationship, regardless of the relationship duration, as shown in Figure 6.

As highlighted in

Table 4. FSFI domains scores; prevalence of FSD in groups with and without hypoglycaemic events during intercourse. (n = number).

“Have You Ever Experienced a Hypoglycaemic Event During Intercourse?”	“No” (n = 24)	“Sometimes/Most of the Times” (n = 44)	“No” vs. “Sometimes/Most of the Times” *
FSFI domains
Desire	3.13 ± 1.24	4.00 ± 1.15	<0.01
Arousal	3.26 ± 2.31	4.19 ± 1.99	0.06
Lubrication	3.51 ± 2.63	4.17 ± 2.13	0.42
Orgasm	3.33 ± 2.42	3.94 ± 2.22	0.22
Satisfaction	3.68 ± 2.07	4.78 ± 1.54	0.03
Pain	3.87 ± 2.72	4.40 ± 2.07	0.78
FSFI total score	20.78 ± 12.56	25.48 ± 9.83	0.13
FSD diagnosis			0.82
Yes	13 (54.2)	25 (56.8)
No	11 (45.8)	19 (43.2)

* p-values related to differences between groups.

, a comparison of subjects that experienced a hypoglycaemic event during intercourse and subjects that did not experience the event demonstrated differences in the desire domain scores and in the satisfaction domain scores (p < 0.01 and p = 0.03, respectively); no statistically significant differences were present in the other FSFI domains and in the FSD prevalence between the two groups.

4. Discussion

The present study aimed to evaluate the association between T1D and FSD. In recent years, many studies have been carried out regarding T1D and FSD [12,13,14,15,16]. The prevalence of FSD in our study was 49.3%, greater than that reported by previous studies. The DCCT and EDIC study, designed with the purpose of comparing different therapeutic regimens in patients with T1D, involved a great number of subjects regardless of their age. Some of the participants were enrolled in an appendix of the study, where they completed a modified version of FSFI questionnaire. The prevalence of FSD was 35.4%, the mean age of the subpopulation was 42.8 years and depressive symptoms and marriage demonstrated a correlation with FSD [18]. Tagliabue et al. found a prevalence of FSD of 33.8% in a population with a mean age of 39.35 years, utilizing the same FSFI questionnaire version of this study [23]. Depressive symptoms and HbA1c lower than 7% demonstrated a correlation with FSD [14]. Maiorino et al. showed a prevalence of 23.3% regarding FSD in a study population with a mean age of 23.3 years [15] and utilizing the same FSFI questionnaire version of this study [23]. Zamponi et al. found a prevalence of FSD of 38.7% utilizing a modified version of FSFI questionnaire with six items (FSFI-6) [25]; the mean age of the population enrolled was 36.4 years [16]. A possible explanation for the more frequent occurrence of FSD in the population of the present study could be due to the involvement of subjects affected by T1D regardless of their age or menopausal status, when most of the other studies presented stricter exclusion criteria. Regarding age ranges, FSD diagnosis appeared to be more frequent in 18–25-year-old group (56.1%) and in >60-year-old group (77.8%) if compared to 26–40-year-old group (26.3%): age is a well-known unmodifiable factor for sexual dysfunction but, in our cohort, a direct correlation between age and FSD was not evident; in fact, a percentage of 56.1% subjects in 18–25 age group presented an FSD diagnosis, which was significantly higher when compared to the 26–40-year-old group. The only domain that demonstrated a direct correlation with age was desire: women in the >60-year-old group showed lower desire when compared with women of other groups. The more frequent occurrence of FSD in subjects between 18 and 25 years could be explained both by a higher frequency of diabetes-related distress and by a sexual-related distress in young ages: it is well-known that young adults present with repercussions on sexual health given by clinical, psychological and dyadic aspects more frequently [26]. In this context, a specific purpose of this study was to focus on the need for educational and supportive interventions regarding sexual health in young subjects. FSD also presented two well-known risk factors, such as menopausal status and use of estro-progestinics: in our cohort, no differences were demonstrated between both subjects in menopause status versus subjects not in menopause and in subjects using estro-progestinics versus subjects not using estro-progestinics. No differences, both in FSD prevalence and in different domains of FSFI, were observed according to the different TIR percentages (using both 50% and 70% as limits to assemble groups) and according to the different HbA1c percentages. Those parameters, largely utilized in the evaluation of glycometabolic control of T1D [6,26], were not associated with sexual dysfunction in the present study; a possible explanation could be that FSD is a multifactorial condition that depends on a great number of factors related to both physical damages caused by hyperglycemia and multiple psychosocial challenges related to living with diabetes [8]. In fact, in the present study, an important difference according to dyadic status was shown in every FSFI domain and in FSD prevalence between the group of subjects not in a relationship and the groups of subjects in a relationship regardless of its duration: 92.3% of the women not in a relationship showed diagnostic criteria for FSD. Another correlation was demonstrated regarding the occurrence of hypoglycemic events during intercourse: the group that experienced the condition presented higher scores in desire and satisfaction domain compared to subjects that did not experience the event; to the best of our knowledge, this was the first study that evaluated the occurrence of hypoglycemic events during intercourse in T1D female subjects. Despite the fact that there is not a specific explanation for the above-mentioned correlation, and that the result does not allow speculations, it is well known that hypoglycemic events and fear of hypoglycemia have a negative impact on the quality of life of subjects affected by T1D [26].

Several limitations can be detected in this study: the lack of evaluation of the potential factors with a demonstrated impact on sexual function and FSD recurrence, such as body mass index, cigarette consumption and psychological factors; data mostly obtained with interval responses and with a self-reported questionnaire; the cross-sectional nature of the study; the lack of a matched control group; considerations about possible population-based sociocultural differences; and the heterogeneity of the subjects enrolled.

5. Conclusions

This study demonstrates a higher prevalence of FSD in subjects affected by T1D regardless of their age. No correlations were demonstrated between sexual dysfunction in women affected by T1D and their different insulin therapy regimens and between sexual dysfunction and conventional parameters utilized in management of T1D, such as TIR and HbA1c percentages. These results bring to light the importance of assessing sexual function in women with T1D, independently from glycometabolic control of the disease, to diagnose female sexual dysfunction in clinical settings. Further studies that overtake the above-mentioned limitations and with a larger population are needed in order to demonstrate the impact of T1D on the occurrence of female sexual dysfunction.