Most open surgeries now have a corresponding laparoscopic approach, which has undeniable advantages over laparotomy in terms of postoperative pain, recovery and patient's reintegration in their previous activities, lower incidence of de novo adhesion formation, shorter hospitalization period, and secondary financial benefits. [1-6]. With regard to the stress that patients are subjected to, although reported less frequently, the efficacy of the laparoscopic approach on postoperative neuroendocrine and immune responses, which largely determines postoperative pain, has not been sufficiently and scientifically proven. Comparative laparoscopy versus laparotomy studies focus on pain monitoring for both methods rather than a prospective comparative evaluation of stress hormones, and there are few studies on stress in these two methods [7, 8] .
The purpose of this study is to objectively assess surgical stress by measuring the hormones released by patients during the surgical approach, document their choice for one or another method, and evaluate its impact on the patient's immediate postoperative course. To the best of our knowledge, this is the first study that evaluates the effect of an invasive method on body stress by monitoring the biochemical markers, such as ACTH, cortisol, β-endorphin, norepinephrine and CRF.
There was no difference in age and size of the excised fibroids between the two groups, but there was a noticeable difference in in surgical time, since the laparoscopic method consumed more time in most operations and this finding is in accordance with the literature . The hospitalization time is a known advantage of the laparoscopic method compared to all types of open myomectomy and this was the case in our material .
Cortisol, a glucocorticoid hormone secreted by the CRH feedback and ACTH from the outer adrenal cortex , plays a key role in regulating the most basic physiological processes, as well as in stress responses [11-15]. In our findings, the hormone differs between the phases before and after surgery, and almost returns to preoperative levels and laparotomy, but not to laparoscopy, where cortisol expression differs only between the first postoperative day and exactly after the procedure. Our results are supported by a recent systematic review and meta-analysis of 71 studies on cortisol stress response in surgery . The cortisol response varies between invasive and minimally invasive procedures, which lack a perioperative increase in cortisol, in contrast to the invasive ones that have more evident cortisol fluctuations in women and elderly patients under open surgery and general anesthesia.
ACTH, on the other hand, distinguishes between phases, before and after surgery, and almost returns to preoperative levels in both groups. There is a difference in expression levels right after surgery with a laparoscopy group having higher mean expression levels than the laparotomy group, which was previously reported .
On the contrary, the differential expression level of noradrenalin was found only on the post-operative day for the two procedures, with lower levels for the laparoscopy group. This finding requires further study.
β-endorphin is an endogenous opioid neuropeptide, but also a peptide hormone produced in the central nervous system (CNS) , which regulates the pain perception of human body mainly used to reduce stress, while maintaining homeostasis . β-endorphin did not show a statistically significant difference between the two groups or during the procedure, which is consistent with the results of previous laparoscopic hysterectomy . The effect of general anesthesia on β-endorphin levels can be considered here .
CRF is a peptide hormone that actively participates in stress responses [22-27]. CRF receptors and CRF itself have been identified in numerous extracellular brain sites . CRF administration has also been shown to trigger activation of the pituitary-adrenal axis and the sympathetic nervous system, as well as stress-related behavioural characteristics . Another difference between the two procedures was the measurement of CRF in the laparotomy group on the first postoperative day, since it was significantly different from the preoperative measurement. Of course, the laparoscopy group generally has a higher mean CRF, but does not change postoperatively which means patients no longer feel pain. This is a substantial difference between both methods in terms of pain and stress indicators. It is well known that CRF exerts analgesic effects in animals [22, 29] and humans [30, 31]. In addition, CRF and stress have been shown to induce the release of opioid peptides in inflammatory tissues [32, 33]. Romero et al. (2017)  clearly demonstrated that deletion of the CRF1 receptor increases the inflammatory response after surgical excision, suggesting that the CRF/CRF1 receptor may be involved in the inflammatory response to tissue injury, which proves that our findings are correct.
A statistically significant difference between the scores on the visual analogue scale for pain (a one-dimensional pain intensity measure) was also notable [35, 36] between the two groups, as the laparoscopic group had lower scores on the first postoperative day. These results are in line with the few studies to date that compare the two procedures with regard to stress [7, 17, 37]. In general, providing a 10 mm altered analgesic on a 100 mm metric VAS scale means a clinically significant improvement or reduction, while a VAS test below 33 mm means that there is an acceptable pain control (i.e., response) after surgery .
The main limitation of this study is the relatively small number of patients, although no related studies have been reported in the literature so far, and it would be interesting to compare other methods and perhaps more factors.
In conclusion, as in previous studies comparing the two methods, it is clear that laparoscopy offers a reduction in pain [1-9, 17, 39-54], and stress level [7, 17, 37]. Our results are in agreement as well, providing a more detailed reference to the relationship between stress hormones and pain between the two surgical procedures. Laparoscopic surgery has been clearly shown to exert significant modifying effect on classical endocrine and metabolic responses, and while more data are needed, the clinical implication of these findings in relation to stress reduction, surgical outcome and active recovery enhances high position of laparoscopy in medical and surgical treatment options.