Options for conservative management as a therapy option of uterine fibroids

Fibroids are the most common benign of the genitals that occurs in women of reproductive age. Their presence varies depending on the age of the woman and her nationality. The incidence in the age of up to 50 years is 70-80%, while in asymptomatic women aged 33 to 40 years in 7.8% Fibroids are benign, monoclonal tumors of the smooth muscle fibers of the myometrium. During their development, they repel the surrounding tissues (myometrium and connective tissue), gradually creating a pseudocapsule rich in collagen fibers (type I and II), fibrous tissue and blood vessels. The following factors are considered to be involved in pathophysiology: 1) Genetic changes: a) chromosomal abnormalities (shifts between chromosomes 12 and 14, deletions on chromosome 7 and trisomy of chromosome) and b) genes related to hormone receptors (hormone receptors) and β, progesterone receptors A and B, growth hormone receptor, prolactin and extracellular substance and collagen, 2) growth factors (eg TGF-β, bFGF, EGF, PDGF, VEGF, IGF and prolactin), 3) hormonal changes, 4) ischemic damage during menstruation. The clinical semiology of fibroids includes one or more of the following: 1) Menorrhagia and / or uterine bleeding (with or without anemia), 2) Pain (dyspareunia, dysmenorrhea, pain due to obstructive or stressful phenomena or degeneration of fibroids), 3) Symptoms from the urinary tract (frequency, nocturia, urgency to urinate, difficulty urinating, urinary incontinence), 4) Symptoms from the gastrointestinal tract (constipation, tension). Alongside they can also contribute to clinical issues such as hypersensitivity, miscarriages and obstetric complications. The treatment of fibroids depends on the symptoms and clinical signs created by their presence, their size and location, on the woman's desire to maintain or not her fertility, her age, the balance between potential risk and benefit, the availability of treatment and the experience of the treating physician. In cases of desire fertility conservative management including also medical therapies offer an effective treatment option. It is distinguished into conservative and invasive. Conservative treatment includes:1) Simple monitoring, 2) Medication: a) Contraceptives (low-dose contraceptives do not increase the size of fibroids, while they are effective in reducing uterine bleeding), Progestogens / Intrauterine device levonorgestrel (natural progesteronen and synthetic progestogens cause endometrial atrophy and therefore may contribute to the reduction of menstrual blood loss in women with fibroids) . The intrauterine device levonorgestrel significantly reduces blood loss during menstruation and uterine volume in women with or without fibroids and is more effective than combined contraceptives in the treatment of menorrhagia), c) Gonadotrophin agonists (GnRHagonists) (fibroids are expected to shrink by 50% within 3 months of treatment, but their use should not exceed 3-6 months within 12 weeks of discontinuation .GnRHagonists are considered useful in some cases to be given preoperatively because they shrink fibroids and reduce anemia caused by uterine bleeding), d) Gonadotropin antagonists (as treatment for fibroids) need further investigation) Danazol (reduces the size of fibroids by 20-25%). Danazole is chemically related to 17-α-ethynyltestosterone, competes with natural androgens, progesterone and glucocorticoids, lowers estrogen levels by lowering GnRH and promotes ovarian steroidogenesis (inhibits androgens reduce the size of fibroids by 46% after 12 weeks of use, but the data on the treatment of women with fibroids are insufficient g) Estrogen receptor antagonists their action is less effective than GnRH agonists, selective estrogen receptor converts SERMS selective progesterone receptor SPRMS, MEFIPRISTONE, Ulipristal acetate Invasive treatment includes minimally invasive methods and surgical methods. Minimally invasive methods include: Uterine artery embolization indicate to improve excessive abnormal uterine bleeding and pelvic flatulence symptoms caused by uterine fibroids It is an imaginatively guided method performed by invasive radiologists. It has fewer complications than the surgical method but shows a 28-32% chance of reoperation (including arterial re-embolization, fibromyectomy, hysterectomy) within the next 4-5 years. Targeted fibroid destruction energy devices: i) MR-guided focused ultrasound, ii) Laparoscopic and ultrasound-guided radiofrequency myolysis, iii) Laser, iv) Microwave Their disadvantage is that they cure one fibroid at a time and that they target the center of the fibroids, but the growth of fibroids is mainly from the periphery. 3) Thermal destruction of the endometrium: This method can be used in women who do not want to maintain their fertility and show abnormal uterine bleeding due to submucosal fibroids. In the future, tissue specific medical therapy ,minimally invasive techniques and pharmacogenetics will offer various directions of fibroid management research and will lead to new future safe and satisfactory therapy options.