1 | INTRODUC TION
Gynoid lipodystrophy (GLD) is one of the most common cosmetic problems, which, according to various data, affects 85%-98% of women aged over 20 years.1,2 The term is used to describe alter¬ations in the topography of the skin. The appeareance resemples a dimpled skin surface or an orange-peel.3 The most common location of such skin changes is the posteriors and outer side of the thighs.4,5
Gynoid lipodystrophy has a multifactorial origin.6,7 Scientists name intrinsic factors among the primary triggers of GLD occur¬rence. These are genetic predisposition, female gender, and race. For instance, European women suffer from GLD more often than Asians and representatives of the Negro race.8,9 Skin deterioration in GLD patients is caused by chronic intoxication, dietary habits (excessive consumption of fats, salt, and fast carbohydrates, leading to insu¬lin resistance), sedentary lifestyle, frequent stress, chronic somatic pathology, and hormonal imbalance.1,10,11 In particular, the problem is compounded under conditions with high levels of estrogen in the blood, such as pregnancy, breastfeeding, and long-term use of oral contraceptives.4,6,12
The main pathogenetic mechanisms of GLD include 1) hyper¬trophy of subcutaneous tissue due to an imbalance in a lipogenesis- lipolysis system with the predominance of lipogenesis, which leads to the accumulation of fat in fat cells (adipocytes)2,6,13; 2) microcircu- latory disorders, such as lymphatic and venous stasis, which lead to increased permeability of the vascular wall with the release of plasma into the interstitial space and occurrence of interstitial tissue edema, hypoxia, and endothelial damages)1,4,13; 3) conjunctive tissue densi- fication due to fibroblast activation, which leads to intensive polym-erization of derma glycosaminoglycans, elevated interstitial pressure, edema enhancement and hypoxia, and facilitates the switch of aero¬bic glycolysis to anaerobic one accompanied by lactic acid production. The excess of lactic acid activates enzymes and substances, initiating qualitative and quantitative transformation of collagen fibers, and fi- brosclerosis in interlobular conjunctive tissue septa with the forma¬tion of micronodules that are visible on the skin surface.3,4,14
Numerous methods of GLD correction are available nowa- days.6 They include physical methods, such as ultrasound, pres- sotherapy, electrostimulation, electrolipolysis, electrophoresis, vibrotherapy, vacuum therapy, endermotherapy, and infrared ir- radiation.15-17 Drug therapy (systemic enzyme therapy, injection techniques),18 external therapy (professional cosmetics for exter¬nal application, wraps),19 and invasive surgical treatment20 are also widely used for GLD treatment. However, despite the variety of available techniques, the chances of success are very limited. In addi¬tion, current GLD treatment techniques give short-term effects.4,9,15 Furthermore, there are no clear protocols for how to regulate the use and combination of different methods, and more in-depth studies are required to investigate the main processes triggered with specific methods. This study aimed to examine pathomorphological and his¬tological changes in subcutaneous tissues in women with GLD follow¬ing a combined compression-vibration treatment with a non-invasive Beautylizer Therapy Cosmoshperes V medical treatment device.2 | MATERIAL AND METHODS
The study involved 25 apparently healthy women aged 25-45 years (average age 36.71 ± 5.14 years) with grade-I and grade-II GLD symptoms. All participants underwent a combined course with com-pression and vibration using a non-invasive Beautylizer Therapy Cosmoshperes V medical treatment device. The observation took 1 month to complete.
Inclusion criteria were patients aged 20-45 years, with grade-I and grade-II GLD, body mass index of 18.50-24.99 kg/m2, who signed voluntary informed consent to participate in the study. Exclusion criteria were as follows: acute or chronic somatic dis¬orders (in the acute stage, sub/decompensation phase); acute or chronic neurological disorders; infection; immunodeficiency; mental illness; cancer; skin lesions; propensity for keloid formation; tattoos in the affected zone; pregnancy; lactation; drug or alcohol abuse; any other cosmetic or therapeutic procedures <6 months before the inclusion in the study; intake of antithrombotic drugs (except for those containing acetylsalicylic acid dose of up to 100 mg/day and clopidogrel in a dose of up to 75 mg per day), as well as immunomod¬ulators, immunosuppressors, immunoglobulins, topical or systemic glucocorticoids, antihistamines, retinoids, vitamin E, and nonsteroi¬dal anti-inflammatory drugs <3 months before being included in the study. The same applies for woman participating in other clinical tri¬als (<30 days prior to study).
All women underwent a thorough screening to exclude the pres-ence of concomitant pathology or exacerbation of existing chronic pathology. Observations included clarification of complaints, history of life and disease, physical and gynecological examination, as well as laboratory (general blood and urine tests, coprogram stool test, and blood biochemistry) and instrumental testing (electrocardiogra¬phy, chest X-ray, abdominal and renal ultrasound, if necessary).
In females with GLD included in the study, local therapy with a combination of compression and vibration was applied with a non-i nvasive Beautylizer Therapy Cosmoshperes V medical device ("Economic Electrical Solutions," Moscow). The device is a high-tech medical apparatus that performs a mechanical action on the skin using spheres of vibration. The therapy course implied 10 sessions for 1 h with a 3-day interval between sessions. The treatment regime was set automatically. At the same time, women followed their reg¬ular lifestyle and their typical diet.
Pathomorphological and histological changes in the subcutaneous fat tissue of women with GLD exposed to a combined compression-vibration treatment were studied using a bioptic punch-size sample from the gluteal fold (in the exposure area) before and after the 10-session treatment course. Biopsy sampling was carried out using a sterile disposable soft tissue biopsy needle STERYLAB (Medical Device Registration Certificate dated December 19, 2017, No. RZN 2017/5967). The biopsy material obtained was further subjected to 22-24-h fixation in a 10% solution of neutral buffered formalin, fol¬lowed by dehydration in alcohol baths with ascending concentration, soaking in xylene, and paraffin embedding. Afterward, 5-6 pm thick ultrafine sections were cut from paraffin blocks with tissue samples on the sledge microtome. The finished sections were treated with xylene to remove paraffin wax.
Tissue preparations obtained after implanted material exposure were studied after scanning glasses using a Leica Apero AT2 scan¬ner and randomly selected slices and four random FOVs. Further, the samples were dehydrated in alcohol baths of descending con-centration and stained with Mayer hematoxylin and eosin. This was followed by repeated dehydration in alcohol baths of ascending con-centration and the placement of sections in the storage environment as a permanent preparation. The results were processed and pre-sented in the Digital Pathology electronic platform.Pathomorphological and histological changes of subcutaneous fat tissues in the bioptic punch-size sample were evaluated as per the following parameters:
- Number/volume of the fat compartment (by the number of adipocytes in the functional lobule/average area of one adi¬pocyte) per unit area of exposure zone;
- The severity of the stromal component (by the size and extent of interlobular junctions) by unit exposure area;
- The ratio of strictly oriented vs. chaotically organized fibers in in-terlobular stromal septa; and
- The density of the vascular component (lumen of microcirculatory blood vessels) per unit area of exposure zone.
Post-treatment results were compared with punch biopsy results prior to treatment initiation.
The data were statistically processed using Student's t-test using SPSS 13.0 software package and Microsoft Excel 2013 (Microsoft, USA). The data were presented as mean (M) ± and standard devi-ations (SD). Samples were checked for normality according to the Shapiro-Wilk method. Differences were considered statistically sig-nificant at a p-value of <0.05.2.1 | Compliance with ethical standards
The study design, its objectives and tasks, the study protocol, pa¬tient information sheet, informed consent form, confidentiality clause, and other aspects were approved by the Ethics Committee of Federal State Budget-Funded Educational Institution of Higher Education “Izhevsk State Medical Academy” of the Ministry of Health of Russia on December 22, 2020.3 | RESULTS
The study found that non-invasive combined compression-vibration therapy with the Beautylizer Therapy Cosmoshperes V device posi-tively affects the subcutaneous fat tissue morphology in women with GLD. A significant decrease (1.83 times, p < 0.05) in average adipocyte size was observed after 10 treatment sessions from the baseline (123.08 ± 13.60 vs. 67.14 ± 4.20 pm, Figure 1, Table 1). At the same time, the average number of adipocytes in the functional fraction of adipose tissue did not change (p > 0.05) and amounted to 16.00 ± 2.00 cells.
Studying the effect of Beautylizer Therapy on the stromal component of subcutaneous tissues in women with GLD also revealed its positive effect on the exposed area. In particular, after a 10-session course of treatment with Beautylizer Therapy Cosmospheres V, a 33.4% increase from baseline in the length of interlobular septa was observed in the bioptic punch-size sample of subcutaneous fat tissues (p < 0.05). In addition, the ratio of strictly oriented/chaotically organized fibers in the interlobular stromal septa changed toward a pronounced prevalence of the former (Figure 2, Table 1).
When assessing microvessels, it was found that Beautylizer Therapy activates microcirculation in the exposure area. Thus, the vascular component per unit area of exposure zone density was sig-nificantly increased (by 32.5%, p < 0.05) in the bioptic punch-size sample of subcutaneous fat tissue in the exposed area compared with pre-t reatment values. The lumen of arterioles increased by 23.1% (p < 0.05) and the lumen of venules by 27.8% (p < 0.05) com¬pared with pre-treatment values (Figure 3).