Quality of life and clinical factors in women with endometriosis, the role of dienogest vs EE/dienogest over time: a single-center study

Endometriosis is a chronic non-malignant estrogen-dependent condition characterized by the presence of endometrial-like tissue outside the uterus affecting 10% of women of reproductive age [1] including very young girls, from all ethnic and social groups [2]. The causes of endometriosis have not yet been determined [3]. Endometriosis is associated with symptoms of dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia [4], up to 50% of women with endometriosis experience infertility [5] with an impairment of QoL [6]. Recent studies consider endometriosis as a disabling condition that may affect the social relationships, mental health, and sexual activity of women [7, 8]. Despite its considerable impact, endometriosis is often under-diagnosed; an Italian study suggests that only 6 out of 10 cases in the general population are diagnosed [9]. There are several factors that can complicate the diagnosis: asymptomatic cases, the late appearance of symptoms and the increased presence of comorbidities with similar symptoms to endometriosis. Symptoms begin during adolescence; thus, treatment is often started several years after use of NSAIDs [10], medical and psychosocial factors contribute to a delayed diagnosis [11]. In this study, we consider the period between the onset of endometriosis symptoms and diagnosis as “Duration Untreated Endometriosis (DUE)”. Among current management approaches, surgery and hormonal drugs are considered as primary treatment to reduce recurrences and to improve the QoL in women suffering from endometriosis [12]. However, medical treatment may be not a permanent solution for symptoms and infertility, so chronic pelvic pain and related symptoms can affect women throughout their fertile life. Pain and infertility may have negative effect on QoL for patients with endometriosis [13]. Škegro et al. showed that higher pain level was related to poorer quality of life [14], emphasizing both physical and psychological aspect of the disease also for treatment project.

A key factor correlated with disease and QoL is the available treatment method. This is one of the most crucial aspects for both physicians and patients, so major consideration should be given not only to efficacy but also to the long-term safety and tolerability of the treatment options that are available [1]. DNG is a synthetic progestin that is currently used for clinical treatment of endometriosis with a dose of 2 mg daily [15], it is an effective and well-tolerated treatment for endometriosis-related pain [16]. It is know that patients are willing to accept the spotting that DNG can cause given the pain relief experienced [17] and may also have positive effects on their QoL and sexual life [18].

Moreover, a reduction of pain was observed in patients using a combination of ethinylestradiol and dienogest in continuous regimen [19] as well as with dienogest alone [17].

Aims of the present study:

This observational, single-center study was conducted on a sample of women with endometriosis referred to a center for diagnosis and treatment of endometriosis with dedicated physicians, psychologists, and nurses, of the Department of Obstetrics and Gynecology at the ARNAS Civico Hospital in Palermo, in Southern Italy, between October 2019 and June 2021.

64 women with endometriosis who completed both time surveys were aged between 19 and 49 years old (M = 32.61 SD = 7.3); 36 of them (56%) took DNG and 28 (44%) took EE/DNG. The descriptive statistics summarizing the participants’ demographic and clinical characteristics in the two treatment groups and the p values for test statistics assessing group differences at baseline are listed in Table 1.

No significant group differences were found except for age of diagnosis (t(62) = 2.48, p < 0.05), and age of onset of first symptoms (t(62) = 2.13, p =  < 0.05). Side effects prevalence was not significant different in both group. Neither at T1 were found significant differences concerning side effects for two groups. The descriptive statistics for psychological and clinical variables between treatment groups at T0 and T1 are listed in Table 2. No significant differences were found for SF-36, EHP-30, ISS, VAS, dysmenorrhea, dyschezia and dyspareunia between the groups.

At T0, one sample T Test found significant differences between the PCS mean values of our sample (M = 40.66 SD = 10.20) and the Italian female standardization sample values (t(63) = – 6.46, p = 0.000) but not at T1 (M = 49.64 SD = 10.70). The MCS mean values were also significantly lower than the mean for the Italian general female population both at T0 (M = 38.02, SD = 11.40) (t(63) = – 4.90, p = 0.000) and at T1(M = 40.98, SD = 12.62) (t(63) = – 2.54, p < 0.05).

In the entire sample, no score was found for significant clinical symptoms for the 11 investigated scales of EHP-30.

Table 3 shows the correlation between psychological variables, VAS and DUE, in all the samples.

This study aimed primarily to assess the relationship between psychological variables, pain and Duration Untreated Endometriosis (DUE) in a sample of women with endometriosis. Second, to evaluate the effect of DNG and EE/DNG on symptoms, QoL, HRQoL, pain and sexual satisfaction in endometriosis patients over time, at 18 months (follow-up). The impact of endometriosis on a woman’s perception of her quality of life is substantial and wide ranging. The sample studied presented low QoL levels for both the mental and physical components compared to Italian standard population, so it represents an important indicator of a disease-related disabling state. The quality of life of women with endometriosis is influenced by many factors. At T0, women described limitations in their physical health, social and personal activities due to emotional and health problems, physical pain, loss of strength and considered their health as poor. Both at T0 and at T1 most patients reported psychological distress, social and personal limitations due to emotional and health problems.

We called the time between the onset of endometriosis symptoms and diagnosis Duration Untreated Endometriosis (DUE) analyzing the relationship with psychological variables. Diagnosis delays have been well documented: Nnoaham [26] reported an average diagnosis delay of 6.7 years, Soliman in 2017 [27] of 4.4 years and in our group; the DUE mean was reduced to 3.59. We consider that our results show both that diagnosis in an endometriosis reference center may be faster and also that, over the last years, there has been an increase of information in the medical–scientific field and hence a reduction in diagnosis time [28]. Our results are in line with the literature, which negatively considers a delay in appropriate treatment both for the QoL of a woman and for progression of endometriosis [29]. We point out that a longer DUE is related to worse HRQoL in different components, showing higher pain perception, work problems, lack of confidence in the medical profession and in treatment. Also PCS was more compromised in women with a longer DUE period: they described higher limitations with regard to physical, social and personal activities because of the disease. At T1 women with longer DUE referred greater impairment regarding pain perception, social support and symptom control and less trust in treatment than women with shorter DUE.

In line with several studies [8, 14], we confirmed the role of pain as an important factor influencing physical, psychosocial or emotional limitations. In our sample, higher pain perception is related to worse QoL as regards the physical component at T0 and both physical and mental components at T1, with more limitations in self-care, physical, social and personal activities, fatigue, distress, emotional problems and poor perception of health. So, according to Pessoa [30], it is important to consider clinical manifestation as central goals in treatment of endometriosis, not only infertility. As concerns HRQoL, we did not find significant clinical alerts of impairment in our group. However, different areas were related to pain both at T0 and at T1, meaning that women that experienced a higher pain level expressed more difficulty in management of pain and symptom controls in their daily activities, mood swings, concern about pains during sexual intercourse, and lack of confidence in treatment. Work difficulties are only related to pain at T0 and misunderstanding by others at T1. Nor, as concerns couples’ sexual problems, did we find clinical levels for all the groups, only a few people reporting significant problems in the sexual area. Couples’ sexual problems were greater when women experienced high pain levels, but only at T1. Poor satisfaction in sexual life worsens the overall quality of life and can lead to anxiety and mood symptoms [31].

As concerns the effect of DNG and EE/DNG over time, we found significant results: dysmenorrhea, VAS, emotional wellbeing, the relationship with the medical profession, and the PCS improved for both the DNG and EE/DNG groups over time. Hence, general and psychological wellbeing can increase in a setting of trust where doctor and patient cooperate to manage the symptoms successfully, regardless of the type of treatment. Moreover, we noted an interaction effect between time and treatment only for dysmenorrhea. Even if dysmenorrhea decreased in both group, patients that took DNG showed a more rapid reduction compared with women that took EE/DNG, DNG treatment works faster than EE/DNG over time in symptom reduction, so, according to the literature, DNG was the best choice in the treatment of dysmenorrhea over time. Techatraisak [32] showed that DNG already improved scores for all EHP-30 scales at month 6 of treatment, until month 24. Caruso [19] considered that DNG was well tolerated with a favorable safety profile until a period of 65 weeks.

Women typically ask how the treatment will improve their symptoms, but they also want to know the possible side effects and it is well know that these can lead to a dropout of the therapy. So, in clinical practice, these are important informational ones to share with patients, counseling patients regarding the expected side effects, weighing up the efficacy and safety of each treatment approach [17].

We agree with the principles of evidence-based medicine that claims that effective and safe medical management of disease is a major clinical aim for the patients with endometriosis. The therapy must be personalized for each patient and also depends on the woman’s goal [12], considering pain as an important problem affecting the QoL of women [33]. As suggested by the NICE guidelines [34], a multidisciplinary approach, including psychologist and a patient association representative, is necessary due to the complexity of the disease and its impact on psychological wellbeing too.

The results of this study highlight that endometriosis causes a general worsening in many areas of the QoL of patients suffering from it. In particular, women with endometriosis show both poor physical and mental components of QoL. Pain perception is associated with worsening of different components of generic QoL, specific HRQoL and sexual problems. DUE is related to worsening of different component of both QoL and HRQoL. As concerns the effect of treatment over time, the current findings demonstrate an improvement in the physical component of QoL, in general pain perception, in different areas of HRQoL (emotional wellbeing, relationship with the medical profession) and in symptoms (dysmenorrhea) using both DNG and EE/DNG. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time. Consequently, as well as improvement in pain symptoms, an improvement in QoL is a crucial aspect in endometriosis toward a global management of the disease.

The results of this study, highlight the need for multidisciplinary approach and clinician education to decrease the effect of endometriosis on women’s QoL and to reduce the duration of untreated endometriosis.