Hysteroscopy is currently the gold-standard procedure in the evaluation of the uterine cavity and treatment of intrauterine lesions as it is minimally invasive and has high diagnostic efficiency [1, 2, 3, 4, 5, 6]. Worth noting is the possibility of removing submucosal myomas by morcellation during hysteroscopy, using tubes of appropriate diameter, while in 2014 the Food and Drug Administration (FDA) issued a warning against performing this procedure during laparoscopic surgery (updates in 2020 and 2022 as a draft - recommended limiting the use of laparoscopic power morcellation to certain appropriately selected women and performing only with a tissue containment system) [6, 7, 8]. Since direct visualization and treatment of lesions can be performed using hysteroscopy, it has replaced uterine cavity curettage procedures [9, 10, 11, 12]. Previously, endoscopes that are 10 mm or more in diameter, a speculum, bullet forceps, and Hegar’s dilators were used in hysteroscopy, which allowed for the dilatation of the cervical canal, necessitating the use of general anesthesia due to the accompanying pain [11, 13]. Nowadays, resectoscopes with a lower diameter are increasingly used to reduce the discomfort experienced by the patient, limit the costs, and shorten the duration of hospitalization [1, 12, 13, 14, 15, 16], which can allow this procedure to be performed without requiring short-term intravenous anesthesia [13, 17].

Anxiety and pain symptoms occur in patients before, during, and after surgery. Currently, preoperative questionnaires are used to assess fear, anxiety, and pain, such as the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the Visual Analogue Scale (VAS). Using these questionnaires, appropriate preoperative treatment and postoperative care can be established [18, 19]. The primary advantage of the APAIS that distinguishes it from other scales is that it assesses, besides the level of anxiety, the level of need for information regarding anesthesia and the procedure, which is extremely important for medical personnel caring for surgical patients [19]. The VAS is a 100-mm-long segment, of which one end is marked with the number 0 and the other end with 10. It is used most often to assess pain; in addition, it is a well-established method in the evaluation of other somatic and psychological symptoms. The major advantages of VAS are its ease of use and patient-friendly characteristic, as well as its very short execution and interpretation time. Due to these features, the VAS can be successfully used to assess and monitor the severity of fear/anxiety/stress in elderly patients and patients with severe clinical conditions [19]. Although short-term stress can be adaptive, pain or nonpain-related stressors can induce maladaptive responses, which in turn can increase cortisol secretion and condition a sensitized physiological stress response [20]. Cortisol and prolactin are described as two potential biochemical markers of chronic stress in the literature [21]. Cortisol is a steroid hormone secreted in the striatal layer of the adrenal cortex [22]. Blood cortisol concentrations show a diurnal rhythm, with the highest concentration observed in the morning (the morning peak of cortisol upon awakening) and the lowest around midnight [23]. Studies on the relationship between severe condition/severe illness or extensive surgical intervention, and serum cortisol levels show an increase in cortisol levels in patients with serious illness or undergoing surgery [24]. However, evaluating the effect of procedures as minimally invasive or “minor” on the concentration of the hormone secreted under stress is difficult. Prolactin is a hormone secreted in the anterior lobe of the pituitary gland [25]. Physiologically, prolactin secretion is regulated by dopamine, and its concentrations show a diurnal rhythm. One of the stimuli to prolactin release is sleep, and other stimuli include physical exertion and emotional state. However, although it is well established that prolactin levels increase in response to stress, the findings of Studerus et al. [26] do not support the notion that increased prolactin levels among patients not previously treated with antipsychotics with a clinically high risk of psychosis or first-episode psychosis are attributable specifically to stress [26]. Severe stress [27] and irregular sleep times and durations may lead to impaired prolactin release. In addition, a “positive coupling” between prolactin levels and the adrenal response to stress stimuli has been reported: the higher the prolactin level, the higher the adrenocorticotropic hormone concentration [28].

With the increase in the availability of ultrasound (US) examinations, the detection of abnormalities within the uterine cavity is also increasing, along with the need to choose the appropriate treatment procedure. According to previous observations, many patients are afraid of minimally invasive procedures performed under general anesthesia. They are also afraid of procedures that, according to them, may be associated with pain. To address this issue, in this study, the levels of stress and anxiety, and biochemical parameters indicating the hormonal response in terms of the stress response in hysteroscopic procedures under local anesthesia were compared with those of traditional surgical procedures and uterine cavity curettage procedures under general, short-term anesthesia.

This study included 184 participants: 153 women undergoing minor gynecological procedures in the Reception Room Office (RRO), i.e., diagnostic or operative mini-hysteroscopy procedures with the use of a hysteroscope of a reduced diameter under local, paracervical anesthesia without the participation of an anesthesiologist, and 31 women undergoing hysteroscopy or uterine cavity curettage in the Central Surgical Office (CSO) under general, intravenous, short-term anesthesia with the participation of an anesthesiologist. All female patients were hospitalized, from February to August 2022, at the Gynecological-Obstetrical Clinical Hospital of the Poznan University of Medical Sciences.

Thanks to the development of minimally invasive techniques, which allow examining individual body cavities, the cervical canal and the uterine cavity can be viewed using small instruments. The use of mini-hysteroscopy, both in reproductive and in peri- and postmenopausal patients, is currently the “gold standard” due to the short hospital stay, short recovery time, integration of clinical practice with the “see and treat” mode, and reduction in the need for additional interventions, such as the need for general anesthesia and performing the procedure in the operating room [1, 2, 3, 4, 5, 29, 30]. Despite the tremendous advances made in mini-hysteroscopy over the past 20 years, many women still experience discomfort and pain in various stages of this procedure, which is the most common factor for treatment discontinuation [31, 32]. Thus, pharmacological and nonpharmacological methods of pain relief are widely used—both during the procedure [2, 32, 33] and in the following hours after the procedure. These pain relief methods are reported to be effective, less effective or non-effective by different groups of women [2, 33, 34, 35, 36, 37].

Different stages of mini-hysteroscopy can result in different unpleasant sensations [38, 39, 40] and different intensities of pain; for example, women who had previously given birth by natural means usually perceive the passage of the hysteroscope through the cervical canal as less painful and the time of the procedure as shorter [29, 41, 42] or the pain level reported by them 60 minutes after procedure is lower [43]. Among the pain relief methods worth citing are the results of a randomized clinical trial conducted in 2021 by Gulucu et al. [44] in which they compared the severity of pain in two groups of women, depending on the temperature of the distension fluid used in the office hysteroscopy (37 °C vs 25 °C). They observed a statistically significant reduction in pain, assessed at specific moments of the procedure using the VAS scale during: the hysteroscope cervical ostium transition, and placement it in the uterine cavity and end of procedure in the group of women in whom the fluid used to dilate the uterine cavity had been pre-heated to 37 °C [44].

It is worth mentioning that the degree of pain experienced by the patient is determined by many factors, such as technical aspects, experience of the operator, abnormalities of the reproductive organs, the total duration of the procedure, and the psychological profile of the patient [10, 34, 45, 46]. A similar relationship was observed in the present study: patients in the RRO group reported more severe pain with the increase in the duration of the procedure. In fact, pain sensations may be compounded by the high level of anxiety felt by women prior to the procedure; anxiety may be a factor that hinders and prolongs the procedure, and it is reflected in the negative experience of the procedure, despite its proper course and smooth execution [2, 6, 42, 43, 47].

To address the complexity of the problem of pain and anxiety in patients undergoing mini-hysteroscopy procedures, the present study attempted to assess the severity of anxiety and stress and pain levels depending on the anesthesia used and simultaneously measure cortisol and prolactin levels before the procedure. Serum prolactin levels are subject to diurnal fluctuations (with the peak secretion around 3 AM), decrease with age, and increase with BMI, and its increase may be related to the stress experienced [48, 49, 50, 51, 52]. In the present study, a decrease in prolactin levels was observed in older patients, which is consistent with the findings of Roelfsema et al. [48] but no relationship between prolactin levels and BMI was observed, and the level of anxiety experienced by the patients before the procedure did not correlate with their serum prolactin levels. A decrease in prolactin levels in relation to the number of deliveries was observed, which is consistent with the study conducted by McCoshen et al. [53].

No significant differences in anxiety intensity and information demand, assessed using the APAIS, were observed between the groups: anxiety about the procedure itself was significantly higher than anxiety about anesthesia among patients in both CSO and RRO groups. Similarly, in both groups, the information demand related to the procedure itself was significantly higher than the information demand related to anesthesia. In both groups, higher levels of anxiety before anesthesia correlated positively with higher levels of anxiety before the procedure. No significant differences in the severity of anxiety and stress measured using the VAS were observed between the study groups.

Serum cortisol levels depends primarily on the circadian rhythm of secretion and the body’s exposure to additional stressors—both, acute and prolonged stress [54, 55, 56]. Direct analysis of cortisol levels in relation to perioperative stress experienced is difficult, as the individual’s personal ability to cope with stressful situations and the psychological and emotional appraisal play an important role in the hormonal response to the stressor [54, 55, 56]. Additionally, the genomic and non-genomic mechanisms of glucocorticoid action in the stress-response were described by Manou-Stathopoulou et al. [56]. Interesting study was conducted by Timmers et al. [57], they showed that an acute stress induction, combining physical and psychological stressors—increased heat pain thresholds, but not tolerance in healthy participants and the magnitude of this stress-induced hypoalgesic effect was predicted by cortisol reactivity and fear of pain. This is encouraging more attention to be paid to placing importance on stress reduction among patients undergoing medical procedures.

In the present study, no significant differences in prolactin and cortisol levels were observed between the study groups. In addition, no correlations between prolactin and cortisol levels before procedure, anxiety and information demand scores, as well as VAS scores for anxiety, stress, and pain were observed. Thus, it can be concluded that the primary factors associated with changes in serum prolactin and cortisol levels are biological and that patients’ feelings of stress and anxiety are mainly related to the procedure itself, rather than the type of anesthesia. Therefore, since performing the procedure under local anesthesia is safer, this solution can be implemented. A systematic review by Gambadauro et al. [42] on patients’ anxiety related to hysteroscopy showed that the increase in the level of anxiety experienced by patients before this minimally invasive procedure was similar to that of patients undergoing major surgery under general anesthesia [42].

Therefore, it can be concluded that it is necessary to apply the interventions that reduce the anxiety of the patients and inform patients about the planned course of the procedure, since higher levels of anxiety before the procedure result in a significant increase in procedure duration, which in turn can increase the pain experienced by the patients.

These should be presented as follows: KCW, KW designed the research study. AN, NIK, MM performed the research. MW provided help and advice on. KCW, KW analyzed the data. KCW, KW wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Patient enrollment methods, ways of obtaining the research material, and its storage were approved by the Bioethics Committee at the Poznan University of Medical Sciences (No 114/22).

Not applicable.

This research received no external funding.

The authors declare no conflict of interest. Karolina Chmaj-Wierzchowska, Katarzyna Wszołek and Maciej Wilczak are serrving as one of the Guest editors of this journal. We declare that Karolina Chmaj-Wierzchowska, Katarzyna Wszołek and Maciej Wilczak had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Gloria Calagna.