- Антропометричні компоненти соматотипу (ендоморфія, мезоморфія та ектоморфія) за методом Heath-Carter та компоненти складу тіла за методом Matiegka в жінок із безпліддям
Антропометричні компоненти соматотипу (ендоморфія, мезоморфія та ектоморфія) за методом Heath-Carter та компоненти складу тіла за методом Matiegka в жінок із безпліддям
Journal Health of Woman. 2025. 6(181): 83-93. doi: 10.15574/HW.2025.6(186).8393
Берестовий О. О.1, Сизоненко А. Р.1,2
1Національний медичний університет імені О.О. Богомольця, м. Київ, Україна
2Київський перинатальний центр, Україна
Для цитування: Berestovyy OO, Sizonenko AR. (2025). Anthropometric components of somatotype (endomorphy, mesomorphy, and ectomorphy) according to the Heath-Carter method and body composition components by the Matiegka method in women with infertility. Ukrainian Journal Health of Woman. 6(181): 83-93. doi: 10.15574/HW.2025.6(186).8393
Стаття надійшла до редакції 14.10.2025 р.; прийнята до друку 20.11.2025 р.
Безпліддя в жінок старшого репродуктивного віку є важливою клінічною та демографічною проблемою. Жіночий репродуктивний потенціал значно знижується після 35 років через прогресуюче старіння яєчників, зниження оваріального резерву та збільшення хромосомних аномалій в ооцитах. Як наслідок, безпліддя стає більш поширеним, а репродуктивні результати дедалі більше залежать від метаболічного статусу, ендокринної регуляції та загального системного здоров'я.
Мета – синтезувати сучасні дані про взаємозв'язок між складом тіла, розподілом жиру та репродуктивними результатами в жінок старшого репродуктивного віку, з особливим акцентом на ролі метаболічних та ендокринних факторів.
Особливу увагу приділено взаємодії між конституційною морфологією тіла (соматотип), параметрами складу тіла та фертильністю, зокрема результати допоміжних репродуктивних технологій. Виявлено існуючі прогалини в літературі щодо комбінованої оцінки соматотипу за методом Heath–Carter та складу тіла на основі підходу Matiegka через жіноче безпліддя. Оцінено обмежені дані про взаємодію між цими конституційними характеристиками та адаптивними реакціями, пов'язаними зі стресом, особливо в умовах тривалого психосоціального стресу. Розроблено концептуальну основу, що інтегрує соматотип, склад тіла, метаболічну регуляцію та адаптивні механізми в контексті жіночої репродуктивної функції, а також обґрунтовано необхідність подальших досліджень, особливо в популяціях, які зазнають таких хронічних стресових умов, як ті, що спостерігаються в Україні.
Висновок. Такі дослідження, особливо проведені в популяціях, які зазнали тривалого стресу, пов'язаного з війною, можуть дати нове розуміння конституційних та адаптивних детермінант жіночої репродуктивної функції та сприяти розробці більш персоналізованих діагностичних та терапевтичних стратегій лікування безпліддя.
Автори заявляють про відсутність конфлікту інтересів.
Ключові слова: соматотип, метод Heath–Carter, склад тіла, ендоморфія, мезоморфія, ектоморфія, жіноче безпліддя, антропометрія, репродуктивна ендокринологія.
ЛІТЕРАТУРА
1. Boddeti S, Noor K, Ansar M, Abera M, Suresh SB et al. (2025). Impact of obesity on in vitro fertilization (IVF) outcomes: a systematic review. Cureus. 17(8): e90695. https://doi.org/10.7759/cureus.90695; PMid:40978884 PMCid:PMC12450106
2. Campa F, Moon J. (2025). Beyond somatotype categories: composition-based clustering of body types in young adults. Frontiers in Physiology. 16: 1722899. https://doi.org/10.3389/fphys.2025.1722899; PMid:41357170 PMCid:PMC12679298
3. Carosso AR, Revelli A, Ruffa A, Carosso M, Contangelo G et al. (2025, May 30). Impact of body fat distribution and insulin sensitivity on in vitro fertilization outcomes: a prospective observational study. Journal of Clinical Medicine. 14(11): 3848. https://doi.org/10.3390/jcm14113848; PMid:40507609 PMCid:PMC12155864
4. Carter JEL. (2002).The Heath-Carter anthropometric somatotype. Instruction manual. Revised ed. San Diego (CA): Department of Exercise and Nutritional Sciences, San Diego State University.
5. Cena H, Chiovato L, Nappi RE. (2020). Obesity, polycystic ovary syndrome, and infertility: a new avenue for GLP-1 receptor agonists. Journal of Clinical Endocrinology & Metabolism. 105(8): e2695-e2709. https://doi.org/10.1210/clinem/dgaa285; PMid:32442310 PMCid:PMC7457958
6. Chaves HL, Schmitz MJ, Francisquini CDS, Rosa VBD, Schuffner A, Furlan JA. (2023, Nov 24). Impact of Body Mass Index and advanced maternal age on in vitro fertilization outcomes. JBRA Assist Reprod. 27(4): 594-601. https://doi.org/10.5935/1518-0557.20230041; PMid:37579267 PMCid:PMC10718551
7. Chen H, Wang WJ, Chen YZ, Mai MQ, Ouyang NY et al. (2010, May). Effects of body mass index and age on the treatment of in vitro fertilization-embryo transfer among patients with non-polycystic ovarian syndrome. Zhonghua Liu Xing Bing Xue Za Zhi. 31(5): 567-571. PMID: 21163039.
8. Chen Y, Li Y, Zhang B, Xia W, Feng X. (2025). Association between relative fat mass and female infertility among reproductive-aged women from NHANES 2013-2020. Scientific Reports. 15: 13334. https://doi.org/10.1038/s41598-025-97243-5; PMid:40246879 PMCid:PMC12006307
9. Chimote B, Chimote N. (2020). Deterioration in baseline reproductive hormone profile is associated with increase in reproductive endocrine disorders: data evaluation in Indian women over a 15-year duration. Fertility and Sterility. Open Archive. 114(3); Suppl: e445. https://doi.org/10.1016/j.fertnstert.2020.08.1284
10. Christofolini J, Maria Christofolini D, Zaia V, Bianco B, Barbosa CP. (2020, Jan). Body fat distribution influences ART outcomes. Gynecol Endocrinol. 36(1): 40-43. Epub 2019 Jun 18. https://doi.org/10.1080/09513590.2019.1630609; PMid:31210070
11. Chua SJ, Danhof NA, Mochtar MH, van Wely M, McLernon DJ, Custers I et al. (2020). Age-related natural fertility outcomes in women over 35 years: a systematic review and individual participant data meta-analysis. Human Reproduction. 35(8): 1808-1820. https://doi.org/10.1093/humrep/deaa129; PMid:32696041
12. Esmaeilzadeh S, Delavar MA, Basirat Z, Shafi H. (2013, Jun 20). Physical activity and body mass index among women who have experienced infertility. Arch Med Sci. 9(3): 499-505. Epub 2013 May 27. https://doi.org/10.5114/aoms.2013.35342; PMid:23847673 PMCid:PMC3701979
13. Fabozzi G., Gualtieri P., Frank G., et al. (2024, Jul). Characterization of body composition by dual energy X-ray absorptiometry (DXA) of infertile women with history of repeated implantation failure. Human Reproduction. 39; Suppl 1: deae108.964. https://doi.org/10.1093/humrep/deae108.964
14. Fernandes A, Gordon A, Sweeting A. (2025). Pre-conception weight loss interventions in women with polycystic ovary syndrome and the effect on perinatal outcomes: a quantitative synthesis of surrogate outcomes. Diabetes, Obesity and Metabolism. 27(12): 7158-7179. https://doi.org/10.1111/dom.70116; PMid:41035114 PMCid:PMC12587233
15. Filippi-Arriaga F, Agarwal N, Rodrigues-Martins D, Monteiro MP, Huvinen E, Suliman SGI et al. (2025). EASO Position Statement: Women with Obesity across the Reproductive Life – Fertility, Preconception, Pregnancy, Postpartum, and Breastfeeding. Obes Facts. 18(6): 625-639. Epub 2025 Jun 21. https://doi.org/10.1159/000546449; PMid:40544836 PMCid:PMC12306975
16. García-Ferreyra J, Carpio J, Zambrano M, Valdivieso-Mejía P, Valdivieso-Rivera P. (2021). Overweight and obesity significantly reduce pregnancy, implantation, and live birth rates in women undergoing in vitro fertilization procedures. JBRA Assisted Reproduction. 25(3): 394-398. https://doi.org/10.5935/1518-0557.20210020
17. Geller S, Levy S, Goldzweig G, Hamiel U, Benyamini Y. (2020). Body image, illness perception, and psychological distress in women with polycystic ovary syndrome. Health Psychol Open. 7(2): 2055102920967358. doi: 10.1177/2055102920967358.
18. Greendale GA, Sternfeld B, Huang M et al. (2019). Changes in body composition and weight during the menopause transition. JCI Insight. 4(5): e124865. https://doi.org/10.1172/jci.insight.124865; PMid:30843880 PMCid:PMC6483504
19. Gonnella F, Konstantinidou F, Donato M, Gatta DMP, Peserico A, Barboni B et al. (2024). The molecular link between obesity and the endometrial environment: a starting point for female infertility. International Journal of Molecular Sciences. 25(13): 6855. https://doi.org/10.3390/ijms25136855; PMid:38999965 PMCid:PMC11241599
20. Hameed H, Hasan SU, Najeeb MN et al. (2023). Impact of obesity on female reproductive hormones and ovulatory function: a clinical and biochemical evaluation of endocrine disruption in women of reproductive age. Pakistan Journal of Medical & Health Sciences. 17(11): 315. https://doi.org/10.53350/pjmhs20231711315
21. Heath BH, Carter JEL. (1967). A modified somatotype method. American Journal of Physical Anthropology. 27: 57-74. https://doi.org/10.1002/ajpa.1330270108; PMid:6049820
22. Heidari Khoei H, Dehdehi L, Moloudizargari M, Baninameh Z, Rezaie-Chamani S, Oliveri Conti G et al. (2016). Female obesity and clinical outcomes of assisted reproductive technologies (ART): an updated systematic review and meta-analysis. International Journal of Medical Research & Health Sciences. 5(11): 157-170.
23. Jiskoot G, Benneheij SH, Beerthuizen A, de Niet JE, de Klerk C, Timman R et al. (2017). A three-component cognitive behavioural lifestyle program for preconceptional weight-loss in women with polycystic ovary syndrome (PCOS): a protocol for a randomized controlled trial. Reproductive Health. 14: 34. https://doi.org/10.1186/s12978-017-0295-4; PMid:28264692 PMCid:PMC5339998
24. Kayatas S, Boza A, Api M, Kurt D, Eroglu M, Arınkan SA. (2014, Jun). Body composition: A predictive factor of cycle fecundity. Clin Exp Reprod Med. 41(2): 75-79. Epub 2014 Jun 30. https://doi.org/10.5653/cerm.2014.41.2.75; PMid:25045631 PMCid:PMC4102693
25. Kim CH, Lee SH. (2022). Effectiveness of lifestyle modification in polycystic ovary syndrome patients with obesity: a systematic review and meta-analysis. Life (Basel). 12(2): 308. https://doi.org/10.3390/life12020308; PMid:35207595 PMCid:PMC8876590
26. Kirchengast S. (2005). Evolutionary and medical aspects of body composition characteristics in subfertile and infertile women. Acta Medica Lituanica. 12(1): 22-27.
27. Kirchengast S, Huber J. (1998). Interactions between somatometric parameters and endogenous hormone levels as well as hormonally induced variations of body composition. Anthropologischer Anzeiger. 56(3): 251-261. https://doi.org/10.1127/anthranz/56/1998/251
28. Kirchengast S, Huber J. (2004). Body composition characteristics and fat distribution patterns in young infertile women. Fertility and Sterility. 81(3): 539-544. https://doi.org/10.1016/j.fertnstert.2003.08.018; PMid:15037399
29. Kozar N, Gavrić Lovrec V, Kovačič B, Reljič M. (2025). Predictive value of AMH in late reproductive age: a retrospective cohort study. Scientific Reports. 15: 21073. https://doi.org/10.1038/s41598-025-07411-w; PMid:40596221 PMCid:PMC12217941
30. Kubikowska N, Landowska M, Kwiatkowska M, Krawczak P. (2025). The impact of lifestyle modifications on polycystic ovary syndrome phenotypes: a narrative review. Archives of Euromedica. 15(5). https://doi.org/10.35630/2025/15/Iss.5.503
31. Lidborg LH, Boothroyd LG. (2025). A systematic review of the association between women's morphological traits and fertility. Evolutionary Human Sciences. 7: e42. https://doi.org/10.1017/ehs.2025.10026; PMid:41445971 PMCid:PMC12722052
32. Li TJ, Pillai N, Yap CG, Jahan NK. (2022). Obesity and female infertility – a review on mechanisms. Open Access Library Journal. 9: e8817. https://doi.org/10.4236/oalib.1108817
33. Liu D, Li L, Sun N, Zhang X, Yin P, Zhang W et al. (2023). Effects of body mass index on IVF outcomes in different age groups. BMC Women's Health. 23(1): 416. https://doi.org/10.1186/s12905-023-02540-8; PMid:37553621 PMCid:PMC10410781
34. Liu D, Luo X, Zhou K. (2025). Association between current relative fat mass and history of female infertility based on the NHANES survey. Scientific Reports. 15: 6294. https://doi.org/10.1038/s41598-025-89417-y; PMid:39984538 PMCid:PMC11845496
35. Liu X, Li W, Wen Y, Xu G, Zhou G, Qu Q et al. (2021, Feb 15). Obesity and Heath-Carter Somatotyping of 3438 Adults in the Xinjiang Uygur Autonomous Region of China by Multivariate Analysis. Diabetes Metab Syndr Obes. 14: 659-670. https://doi.org/10.2147/DMSO.S287954; PMid:33623401 PMCid:PMC7894874
36. Liu Y, Tilleman K, Vlaeminck B, Gervais R, Chouinard PY et al. (2022, Jul 25). The fatty acid composition in follicles is related to the developmental potential of oocytes up to the blastocyst stage: a single-centre cohort study. Reprod Biol Endocrinol. 20(1): 107. https://doi.org/10.1186/s12958-022-00974-7; PMid:35879714 PMCid:PMC9310456
37. Loy SL, Cheung YB, Soh SE, Ng S, Tint MT, Aris IM et al. (2018). Female adiposity and time-to-pregnancy: a multiethnic prospective cohort. Human Reproduction. 33(11): 2141-2149. https://doi.org/10.1093/humrep/dey300; PMid:30285230 PMCid:PMC6201836
38. Maheshwari A, Stofberg L, Bhattacharya S. (2007). Effect of overweight and obesity on assisted reproductive technology – a systematic review. Hum Reprod Update. 13(5): 433-444. https://doi.org/10.1093/humupd/dmm017; PMid:17584821
39. Mahoney D. (2014). Lifestyle modification intervention among infertile overweight and obese women with polycystic ovary syndrome. Journal of the American Association of Nurse Practitioners. 26(6): 301-308. https://doi.org/10.1002/2327-6924.12073; PMid:24170708
40. Malhotra R, Garcia de Paredes J, Smith A, Chemerinski A, Doshi D, Morelli SS. (2025). Obesity epidemic and its impact on female fertility: current understanding and future directions. Cureus. 17(7): e87283. https://doi.org/10.7759/cureus.87283
41. Malinina O, Chaika H, Taran O. (2021). Features of anthropometric parameters in women of different morphotypes with polycystic ovary syndrome. Georgian Medical News. 311: 41-45.
42. Marinelli S, Napoletano G, Straccamore M, Basile G. (2022, Aug 31). Female obesity and infertility: outcomes and regulatory guidance. Acta Biomed. 93(4): e2022278. doi: 10.23750/abm.v93i4.13466. PMID: 36043953; PMCID: PMC9534231.
43. Mastaglia SR, Solís F, Oliveri B et al. (2012). Increase in android fat mass with age in healthy women with normal body mass index. Journal of Clinical Densitometry. 15(3): 273-277. https://doi.org/10.1016/j.jocd.2011.12.006; PMid:22402116
44. Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. (2007, Nov). Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online. 15(5): 532-538. https://doi.org/10.1016/S1472-6483(10)60385-9; PMid:18044034
45. Moreno-Ortiz H, Acosta ID, Lucena-Quevedo E, Arias-Sosa LA, Dallos-Báez AE et al. (2018). Ovarian reserve markers: an update. In: Ovarian Reserve and Infertility. London: Intech Open. https://doi.org/10.5772/intechopen.75521; PMid:29313278 PMCid:PMC5904072
46. Özcan Dağ Z, Dilbaz B. (2015). Impact of obesity on infertility in women. Journal of the Turkish German Gynecological Association. 16(2): 111-117. https://doi.org/10.5152/jtgga.2015.15232; PMid:26097395 PMCid:PMC4456969
47. Pinborg A, Gaarslev C, Hougaard C, Nyboe Andersen A, Andersen PK et al. (2011, Oct). Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples. Reprod Biomed Online. 23(4): 490-499. Epub 2011 Jun 26. https://doi.org/10.1016/j.rbmo.2011.06.010; PMid:21856228
48. Practice Committee of the American Society for Reproductive Medicine. (2014). Female age-related fertility decline. Fertility and Sterility. 101(3): 633-634. https://doi.org/10.1016/j.fertnstert.2013.12.032; PMid:24559617
49. Practice Committee of the American Society for Reproductive Medicine. (2021). Obesity and reproduction: a committee opinion. Fertility and Sterility. 116(5): 1266-1285. https://doi.org/10.1016/j.fertnstert.2021.08.009; PMid:34538460 PMCid:PMC8354803
50. Rafael F, Rodrigues MD, Bellver J et al. (2023, May). The combined effect of BMI and age on ART outcomes. Human Reproduction. 38; 5: 886-894. https://doi.org/10.1093/humrep/dead042; PMid:36928306
51.Rathnayake N, Rathnayake H, Lekamwasam S. (2022). Age-related trends in body composition among women aged 20-80 years: a cross-sectional study. Journal of Obesity. 2022: 4767793. https://doi.org/10.1155/2022/4767793; PMid:35154825 PMCid:PMC8828324
52. Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J et al. (2014). Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. International Journal of Reproductive Medicine. 2014: 719050. https://doi.org/10.1155/2014/719050; PMid:25763405 PMCid:PMC4334071
53. Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES. (2011, Jul). Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol. 118(1): 63-70. https://doi.org/10.1097/AOG.0b013e31821fd360; PMid:21691164
54. Shareif M, Abd AH. (2019). Relationship between obesity and anti-Müllerian hormone in women above 35 years old. European Journal of Pharmaceutical and Medical Research. 6(4).
55. Shukla A, Rasquin LI, Anastasopoulou C. (2025, Jul 7). Polycystic ovarian syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Updated 2025 Jul 7.
56. Singh S, Pal N, Shubham S, Sarma DK, Verma V et al. (2023). Polycystic ovary syndrome: etiology, current management, and future therapeutics. Journal of Clinical Medicine. 12(4): 1454. https://doi.org/10.3390/jcm12041454; PMid:36835989 PMCid:PMC9964744
57. Skowrońska M, Pawłowski M, Buczyńska A., Wiatr A, Dyszkiewicz A, Wenta A et al. (2024, Nov 29). The relationship between body composition parameters and the intake of selected nutrients, and serum anti-Müllerian hormone (AMH) levels in the context of ovulatory infertility. Nutrients. 16(23): 4149. https://doi.org/10.3390/nu16234149; PMid:39683543 PMCid:PMC11644442
58. Su HI, Sammel MD, Freeman EW, Lin H, DeBlasis T, Gracia CR. (2008, Sep-Oct). Body size affects measures of ovarian reserve in late reproductive age women. Menopause. 15(5): 857-861. https://doi.org/10.1097/gme.0b013e318165981e; PMid:18427357 PMCid:PMC2821936
59. Szkodziak P, Szkodziak F, Trzeciak K, Woźniak S, Mlynarczyk M, Paszkowski T. (2025). Insulin resistance in polycystic ovary syndrome phenotypes and the vicious cycle model in its etiology. Scientific Reports. 15: 42649. https://doi.org/10.1038/s41598-025-26718-2; PMid:41315368 PMCid:PMC12663220
60. Tang Q, Zhang Q, Xia R, Li X, Du J et al. (2025). Association of relative fat mass with female infertility. Scientific Reports. 15: 22713. https://doi.org/10.1038/s41598-025-08595-x; PMid:40595186 PMCid:PMC12215735
61. Teede HJ, Misso ML, Costello MF et al. (2023). International evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction. 38(9): 1655-1688.
62. Turner F, Powell SG, Al-Lamee H, Gadhvi A, Palmer E, Drakeley A et al. (2020). Impact of BMI on fertility in an otherwise healthy population: a systematic review and meta-analysis. BJOG. 127(6): 715-725. https://doi.org/10.1111/1471-0528.16171; PMid:32048421
63. Tziomalos K, Dinas K. (2018). Obesity and outcome of assisted reproduction in patients with polycystic ovary syndrome. Frontiers in Endocrinology (Lausanne). 9: 149. https://doi.org/10.3389/fendo.2018.00149; PMid:29670581 PMCid:PMC5893828
64. Vural F, Vural B, Çakıroğlu Y. (2016). In vitro fertilization outcomes in obese women under and above 35 years of age. Clinical and Experimental Obstetrics & Gynecology. 43(2): 233-237. https://doi.org/10.12891/ceog2080.2016
65. Wang X, Zhu R, Han H, Jin J. (2023). Body fat distribution and female infertility: a cross-sectional analysis among US women. Reproductive Sciences. 30(11): 3243-3252. https://doi.org/10.1007/s43032-023-01280-2; PMid:37277689
66. Wass P, Waldenström U, Rössner S, Hellberg D. (1997, Sep). An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer. Hum Reprod. 12(9): 2057-2060. https://doi.org/10.1093/humrep/12.9.2057; PMid:9363729
67. Wu S, Jiang H, Wang X, Meng Y, Lai S, Wan J. (2025). Waist-to-hip ratio and female infertility: an observational study and Mendelian randomization analysis. Medicine (Baltimore). 104(47): e45815. https://doi.org/10.1097/MD.0000000000045815; PMid:41305717 PMCid:PMC12643627
68. Yang Q, Wuliu J, Zeng L, Huang J, Tang G, Zhang J et al. (2024). Association between a body shape index and female infertility. BMC Women's Health. 24: 486. https://doi.org/10.1186/s12905-024-03335-1; PMid:39227849 PMCid:PMC11373282
69. Yu C, Wu H, Sun X, Cao M, Yuan J. (2025, Jun 23). The association between obesity-related indicators and female infertility: the United States National Health and Nutrition Examination Survey, 2013-2018. Front Endocrinol (Lausanne). 16: 1588965. https://doi.org/10.3389/fendo.2025.1588965; PMid:40626237 PMCid:PMC12229851
70. Yu KQ, Zhao WQ, Zhang T. (2025). Comparative analysis of five obesity-related indicators for predicting infertility in U.S. adults. Frontiers in Nutrition. 12: 1593706. https://doi.org/10.3389/fnut.2025.1593706; PMid:40630166 PMCid:PMC12234334
71. Zaadstra MB, Seidell J, Van Oord PAH et al. (1993). Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. British Medical Journal. 306: 484 https://doi.org/10.1136/bmj.306.6876.484; PMid:8448457 PMCid:PMC1676805
72. Zabulienė L, Urboniene J, Tutkuvienė J. (2013). Body composition of lean women with polycystic ovary syndrome. Anthropological Review. 76(4): 369-380. https://doi.org/10.2478/anre-2013-0018
73. Zhang JJ, Feret M, Chang L, Yang M, Merhi Z. (2015). Obesity adversely impacts the number and maturity of oocytes in conventional IVF not in minimal stimulation IVF. Gynecological Endocrinology. 31(5): 409-413. https://doi.org/10.3109/09513590.2015.1014785; PMid:25856299