Uterine fibroids are the most common benign tumors of the reproductive organ. Despite the increasingly available knowledge regarding the associated problems, it still seems to be an undervalued issue [1]. It is estimated that uterine fibroids occur in over 40% of women over 35 years of age. Research results vary, but the total incidence of fibroids in women of reproductive age is estimated at up to 70% in certain populations [2]. The pathophysiology of uterine fibroids, although still unknown, is multifactorial. The recognized factors that may modify the formation and growth of these tumors include age, black race, hormonal disorders or lifestyle-related factors, such as the level of physical activity or diet [3]. In most patients, the presence of uterine fibroids is asymptomatic, but in a certain group of patients these lesions cause problems that require a variety of medical interventions, such as pharmacological or surgical treatment [3,4,5]. The most common symptoms associated with fibroids include: anemia secondary to heavy menstrual bleeding, pain within the lesser pelvis, painful menstruation. Fibroids may also contribute to infertility or pregnancy-related disorders, but these just constitute some of the wide range of symptoms [6]. Importantly, all the symptoms may significantly affect the quality of patients’ lives [7].

As these are hormone-dependent gynecological tumors, the development of uterine fibroids depends on sex steroids, i.e., estrogens. Moreover, progesterone is becoming a more common focus of researchers discussing the conditions underlying the development of these tumors [8]. Recent research has highlighted the potential contribution of progesterone to the pathophysiology of uterine fibroids. Progesterone may interact with growth factors, such as epidermal growth factor (EGF), transforming growth factor beta-3 (TGF-beta3), and insulin-like growth factor-1 (IGF-1), thereby promoting the proliferation and survival of fibroids. Another possible action is linked to progesterone-related progenitor stem cell activity. Furthermore, progesterone may be responsible for the regulation of angiogenesis. At the fibroma level, the number of progesterone receptors was found to be elevated. In summary, progesterone appears to play a pivotal role in the growth of uterine fibroids [9, 10].

The GH (growth hormone)– IGF-1 (insulin-like growth factor 1) axis plays a key role in the regulation of cell growth, cell differentiation and death, and, what follows, in the development and metabolism of the entire human body. IGF-1 has anti-apoptotic properties– it stimulates the cell cycle and cell division. It is also a promoter of angiogenesis [11]. Some authors indicated the important role of IGF-1 and GH in the pathogenesis of tumors. It is believed that this axis is able to move already transformed cells through subsequent phases of the cell cycle. Viral and cellular oncogenes require an intact IGF-1 signaling pathway to induce transformation [10]. Influencing this axis provides certain possibilities of oncological therapy [12, 13].

According to some authors, IGF-1 may be a factor that promotes the proliferation of uterine fibroid cells. For example, IGF-1 receptors were shown to be overexpressed in fibroid tissues, compared to the myometrium [14]. To date, the participation of increased IGF-1 concentration has been suggested in the pathophysiology of the formation of the tumors [15]. An increased expression of the IGF-1 receptors in the fibroid tissue may also be associated with the promotion of angiogenesis and partially underlie the pathophysiology of heavy menstrual bleeding in patients with uterine fibroids [16].

Acromegaly is an example of a disease characterized by an increased concentration of GH and IGF-1. The manifestations of acromegaly are caused by an increased GH secretion by pituitary tumor and, as a consequence, increased IGF-1 levels. It was also confirmed that the severity of disease symptoms as well as the frequency of complications and GH concentrations were positively correlated with both the duration of the disease and the size of the pituitary tumor [17]. Acromegaly is a rare disease with an overall incidence ranging between 2.8 and 13.7 cases per 100,000. The incidence is 0.2–1.1 cases/year/100,000 people. The peak of acromegaly diagnoses is noted in the 5th decade of life and the average age at diagnosis is 40.5–47 years. The diagnosis is most often made about 5 to 10 years after the onset of the first symptoms [18]. However, recent research has suggested a higher prevalence than previously assumed, i.e., 85/106 [19, 20].

Regrettably, despite the growing awareness of physicians and patients, the diagnosis of acromegaly is still delayed even though the manifestations of the disease are rather characteristic [21]. These mostly include changes in the external appearance, such as the enlargement of the hands, feet, the facial part of the cranium, coarse facial features, weight gain with changes in body composition characterized by ectopic lipid deposition in muscles and reduced visceral adiposity and intrahepatic lipid, as well as organomegaly, soft tissue or bone enlargement [22, 23]. It was also demonstrated that the disease and its complications significantly reduced the quality of patients’ lives [24].

An important role in the diagnosis of acromegaly is played by the above-mentioned growth factor, i.e., IGF-1. The measurement of serum IGF-1 levels is crucial in the diagnosis of acromegaly in patients with suspected disease based on clinical symptoms along with the oral glucose toleration test-induced GH suppression as a confirmation test [25]. IGF-1 is also an indicator of acromegaly activity; its serum level, in correlation with GH level is useful in monitoring disease progression [26, 27].

It is estimated that untreated acromegaly may reduce the average survival time by about 10 years. Early diagnosis and treatment of the disease is crucial due to the numerous complications that untreated acromegaly may lead to [28]. The most dangerous of those complications, apart from cardiovascular and respiratory issues, include the increased occurrence of both benign and malignant tumors. Therefore, it is important to note that cancer became the leading cause of death in the group of patients with acromegaly in the last decades [29].

The occurrence of tumors in patients with acromegaly has been the subject of numerous studies. Data from previous studies are strongly inconclusive in this area. Some authors confirmed a higher incidence of neoplasms in patients with acromegaly [30,31,32,33], while others showed that the overall risk of cancer in patients with acromegaly might not differ at all from the risk in the population [34]. A four-fold increase in the incidence of kidney and bladder cancer was demonstrated in a group of patients with acromegaly [35]. Moreover, an increase in the incidence of colorectal cancer was also found, which was confirmed in other studies as well [36]. Interestingly, no increase in tumor-related mortality was noted. Conversely, another study showed no increased incidence of thyroid, respiratory, brain, breast or prostate tumors in patients with acromegaly [35]. However, the available data are inconclusive, as other studies suggested an increased incidence of thyroid diseases in patients with acromegaly, including the aforementioned thyroid cancer [37]. Some authors suggested only a slightly elevated overall risk of cancer in patients with acromegaly [38]. Nevertheless, according to current guidelines, screening colonoscopy at the diagnosis is recommended [39].

The potential impact of the GH-IGF-1 axis on the formation of fibroids, which was demonstrated in basic research [14], determines the need to assess the frequency of this pathology in a group of patients with acromegaly. The authors of one of few available studies on uterine fibroids in patients with acromegaly indicated a possible association of acromegaly with an increased risk of developing this pathology. It should be emphasized that the study was conducted in a group of only 25 patients [40]. However, contrary to this hypothesis, the results of some studies confirmed no such relationship [41]. The data seem to be of limited strength, even considering the fact that acromegaly is a rare disease. The hypothesis regarding the relationship between fibroids and acromegaly was not verified in any subsequent study or in a larger population. Therefore, such views remain unchanged and are passed on to subsequent generations of gynecologists.

The relationship between acromegaly and tumor formation in the reproductive system remains ambiguous. Currently available research results are insufficient to draw clear conclusions and leave room for further research. In this paper, we aimed to examine the available data concerning the relationship between the GH–IGF-1 axis and uterine fibroids.