Original Article Gynecol Obstet Invest 2015;79:229–233 DOI: 10.1159/000368776

Received: July 15, 2014 Accepted after revision: October 1, 2014 Published online: January 14, 2015

Endometriosis and Perceived Stress: Impact of Surgical and Medical Treatment Lucia Lazzeri a Cinzia Orlandini a Silvia Vannuccini a Serena Pinzauti a Claudia Tosti a Errico Zupi a Rosella Elena Nappi b Felice Petraglia a a

Department of Molecular and Developmental Medicine, University of Siena, Siena, and b Research Center for Reproductive Medicine, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

Abstract Background: The aim of the study was to investigate the levels of perceived stress in a group of women with a longterm history of endometriosis in conjunction with surgical and/or medical treatments. Methods: A clinical trial was conducted at the Department of Molecular and Developmental Medicine, University of Siena, in collaboration with a nonprofit association of women with endometriosis, A.P.E. Onlus. Patients (n = 204) with a previous diagnosis of endometriosis (for at least 3 years) were included in this study. Each patient completed a semi-structured questionnaire and a validated scale to assess perceived stress, the Perceived Stress Scale (PSS) by e-mail. Results: The study showed that in women with a long-term history of endometriosis, the level of perceived stress was increased by repeated surgical treatments and reduced by some medical treatments. The median PSS value was 23 (range 9–36) and 30.6% of the study population were included in the highest stress category (>26). The highest levels were found in patients who had undergone the most surgery. The use of progestins was associated with a lower perceived stress (p = 0.004) than in the patients treated with gonadotropin-releasing hormones. Conclusions: Long-term endometriosis has a relevant impact on perceived stress, in particular in those undergoing repeated surgery. © 2015 S. Karger AG, Basel

© 2015 S. Karger AG, Basel 0378–7346/15/0794–0229$39.50/0 E-Mail [email protected] www.karger.com/goi

Introduction

Endometriosis is a chronic disease causing dysmenorrhoea, chronic pelvic pain, dyspareunia and infertility. The clinical and psychological aspects of the disease impair the work capacity, social interaction and family life of patients [1, 2]. Indeed, endometriosis has a crucial impact on daily life and physical functioning (e.g. sleeping, eating and moving) [3–5], and the associated reduced energy and vitality [4] have a negative impact on social and sexual life [6–9]. There is no definitive treatment for endometriosis, either surgical or medical, and the main goal of management is to relieve symptoms by removing endometriotic lesions and/or limit the consequences of their growth [10]. All these conditions affect the mental health of women with endometriosis [11]. In particular, pain induces significant elevated sympathetic nervous system activity and is considered a stressor [12, 13]. Acute stress induces analgesia, but the effect of chronic stress upon nociception is less predictable; stressful experiences may alter pain thresholds by either reducing or exacerbating pain. Stressinduced responses involve the release of various hormones, neurotransmitters and neuromodulators which initially protect, but when this becomes chronic, it may damage the human body [14–16]. The hypothalamic-pituitary-adrenal axis plays a pivotal role in the coordinated physiological response to stress. Following chronic stress exposure, ‘stress-related syndromes’ such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, Lucia Lazzeri, MD Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci IT–53100 Siena (Italy) E-Mail lucialazzeri @ email.it; lucia.lazzeri @ unisi.it

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Key Words Endometriosis · Perceived stress · Surgery

100 90

Very high level 30.8%

80 Women affected (%)

70 60

High level 40.6%

50 40 30 20

Moderate level 28.6%

10 0

Methods

Statistical Analysis All statistical data were collected in a computerized database. Statistical analysis was performed using the MedCalc® package (version 12.4.0.0). Statistically significant differences were determined by means of the Mann-Whitney U test and Wilcoxon test as appropriate. p < 0.05 was considered statistically significant for all comparisons.

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Fig. 1. PSS categories.

40

*

35 30 PSS score

A trial was conducted from June to September 2013 by the Department of Molecular and Developmental Medicine, University of Siena, and A.P.E. Onlus, a non-profit association of women with endometriosis. The study was approved by the institutional review board of the University of Siena. The inclusion criterion was a histological diagnosis of endometriosis (for least 3 years). All women (n = 204) aged 35 ± 8 years (mean ± SD) completed an online questionnaire which consisted of 2 parts: a semi-structured interview including clinical history, characteristics of menstrual cycles, painful symptoms, parity, medical treatment and the number of previous surgical interventions for endometriosis and completion of the Perceived Stress Scale (PSS), a widely used psychological instrument for measuring the global perception of stress. It is a measure of the degree to which situations in one’s life are appraised as stressful [23]. The PSS items were designed to tap how unpredictable, uncontrollable and overloaded respondents find their lives. The scale also includes a number of direct queries about current levels of experienced stress. Moreover, the questions are of a general nature and hence are relatively free of content specific to any sub-population. The PSS was designed for use in community samples with at least a junior high-school education. The items are easy to understand, and the response alternatives are simple to grasp. PSS scores are obtained by reversing responses (e.g. 0 = 4, 1 = 3, 2 = 2, 3 = 1 and 4 = 0) to the 4 positively stated items (items 4, 5, 7 and 8) and then summing across all scale items. The score was divided into 4 different categories (ranging from 0 to 40 points): • 0–6: a low level of stress • 7–19: a medium level of stress • 20–25: a high level of stress • ≥26: a very high level of stress The location of endometriosis was found to be: 30% ovarian, 25% mixed ovarian and peritoneal, 25% mixed ovarian and deep and 20% deep endometriosis. Exclusion criteria were a history of major neurological or psychiatric disease and current or previous abuse of alcohol or recreational substances. The questionnaire also evaluated the existence of other possible factors affecting stress (e.g. mood disorders and chronic diseases) and patients with these were excluded from the study.

PSS score

*

25 20 15 10 1

2

–3

Number of surgical procedures

Fig. 2. Correlation between the number of surgical procedures and

PSS score.

Results

When considering all the patients, the median PSS value was 23 (range 9–36), with 30.6% of the study population included in the highest stress category (>26; fig. 1). All patients underwent surgery at least once, with a range of between 1 and 5 operations. A statistical correlation was found between the number of surgical procedures and PSS; as the number of interventions increased, the PSS score increased (p < 0.001; fig. 2). The time between clinical diagnosis and completion of the questionnaire ranged between 5 and 9 years, with women with a longer history of endometriosis having a higher PSS score (p < 0.0001). Lazzeri/Orlandini/Vannuccini/Pinzauti/ Tosti/Zupi/Nappi/Petraglia

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anxiety and depression, migraine and autoimmune disorders may result [17–21]. Women with endometriosis have higher levels of perceived stress with respect to controls as well as to subjects with chronic pelvic pain of moderate intensity [22]. The use of more objective measures of stress precipitated this study, to investigate the levels and the changes of perceived stress in a group of women with chronic endometriosis in conjunction with medical or surgical treatment.

52%

45.5%

33.2%

43% 31.8%

14.8% GnRH (n = 27)

9.8% P (n = 66)

E/P (n = 51)

Medical treatment

Fig. 3. Distribution of patients with different medical treatments and

the impact on PSS (n = 144). E/P = Estroprogestins; P = progestins.

The questionnaire revealed that 71.5% of the women had been on a medical treatment for endometriosis for at least 6 months, with 35.6% on estroprogestins, 45.3% on progestins and 19.1% on gonadotropin-releasing hormone (GnRH) analogues. The use of progestins was significantly associated with a large percentage of patients with a moderate PSS score and a limited number with a high PSS score (p = 0.004). Among the patients treated with hormonal therapy, GnRH analogues were related to the main percentage of women in the high-level PSS category, while patients receiving estroprogestins were mostly in the high and moderate category (fig. 3).

Discussion

This study showed high levels of perceived stress in women with a long-term history of endometriosis and a high number of repeated surgical procedures. The effect of medical treatments on their perceived stress was evaluated, and women treated with progestins had a lower level of this than those treated with GnRH analogues or oral contraceptives. Women with a long-term history of endometriosis showed the highest levels of perceived stress, suggesting that the chronicity of the disease (persistence and/or recurrence) represents a major factor affecting the perception of stress, independent of pain perception or the severity of the disease. The number of previous surgical procedures for endometriosis has a significant impact on the perception of stress. Although Endometriosis and PSS

the surgical excision of endometriosis lesions may result in an improvement in symptoms, our study revealed that an increasing number of interventions correspond with a very high level of perceived stress, suggesting a potential negative role of the repetitive surgery on psychological well-being. Surgical procedures should be modulated according to clinical characteristics (pain experienced, a wish to fall pregnant or obstructive symptoms) according to the specific duration of the disease, in order to avoid repetitive surgery and to preserve fertility. For these reason, the patient must be informed about the negative effects of surgery and the possibility of recurrence. Surgery should be postponed and medical therapy may be proposed until pregnancy is desired, in order to preserve the ovarian follicular reserve as much as possible [24] and to reduce recurrences [25]. This conclusion is based on our group of patients and has yet to be confirmed by a larger series of patients. Endometriosis is a chronic hormone-dependent disease and may be considered both a consequence of a stress disorder and the cause of a chronic stress condition. Chronic stress induces a dysregulation of neuroendocrine mechanisms and is involved in the pathogenesis of a variety of maladaptive syndromes such as inflammatory bowel disease, anxiety, depression, autoimmune disorders [26–30] and endometriosis [22, 31]. Endometriosis, like these other syndromes, is characterized by elevated levels of cytokines, decreased apoptosis and cell-mediated abnormalities [10]. A co-existence of endometriosis and chronic stress-related diseases (e.g. inflammatory bowel disease, mood disorders and autoimmune disorders) has been shown previously [32, 33], with chronic stress negatively influencing and possibly worsening the course of the endometriosis [19]. Women with endometriosis may bear the pain for a long time with deterioration of their quality of life and their physical and psychological wellbeing [34], which can influence sexual activity and sexual satisfaction with a reduction in libido. The issues of women’s mental health and sexual life should receive more focus to create a better treatment outcome [35]. The ability to individualize the timing of endometriosis treatment, with an integration of medical and surgical strategies, facilitates correct management of the disease to improve the quality of life of the women affected [36]. Medical therapy has the aim of reducing pain by reducing the impact of the disease on quality of life [37–39]. This study shows that medical treatments affect the perception of stress. GnRH analogues were associated with the highest PSS scores and this finding may be explained by their multiple side effects. Progestin use resulted in moderGynecol Obstet Invest 2015;79:229–233 DOI: 10.1159/000368776

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Women affected (%)

22.7%

Very high High Moderate 47.2%

ate PSS scores, supporting the concept that progestins may be used for a possible long-term therapy [40]. The elevated levels of perceived stress detected in our series strongly suggests that the chronicity of endometriosis strongly affects the mechanisms of stress to varying extents, and that correct management (medical and surgical) may improve the stress-related symptoms. The assessment of coping strategies and psychosexual treatment should form part of the clinical management for women with long-term endometriosis.

Acknowledgements The authors would like to thank the Italian non-profit association of women with endometriosis, A.P.E. Onlus, for its collaboration in filling out the on-line questionnaire.

Disclosure Statement The authors report no declarations.

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Endometriosis and perceived stress: impact of surgical and medical treatment.

The aim of the study was to investigate the levels of perceived stress in a group of women with a long-term history of endometriosis in conjunction wi...
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