Cutaneous manifestation of polycystic ovary syndrome
https://doi.org/10.4081/dr.2021.8799
Submitted: 17 July 2020
Accepted: 25 March 2021
Published: 15 September 2021
Accepted: 25 March 2021
Abstract Views: 1985
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
The aim of this cross-sectional study, that included 146 polycystic ovary syndrome (PCOS) patients, was to evaluate the prevalence, severity and pattern of cutaneous manifestation in Jordanian women with PCOS, as well as their correlation with hormonal abnormalities. A thorough complete cutaneous examination, hormonal assays (Luteinizing hormone [LH], follicle stimulating hormone [FSH], prolactin, total testosterone, free testosterone, dehydroepiandrosterone sulfate) and pelvic ultrasonography were done. The most common cutaneous features of PCOS were acne vulgaris (75.3%) followed by hirsutism (59.6%) then seborrhea (43.2%) and androgenetic alopecia (42.5%). Patients who had acne vulgaris presented at a younger age than patients who did not. Patients who had androgenetic alopecia and stria were older than patients with no such features. Moreover, all cutaneous manifestations of PCOS, except for acne, were associated with higher body mass index (BMI). Elevated LH:FSH ratio of more than 2:1 was the most common hormonal abnormality, followed by increased LH and total testosterone. Acne, hirsutism, androgenetic alopecia, seborrhea, acanthosis nigricans and skin tags are common cutaneous manifestations among Jordanian patients with PCOS. The existence of one or more of these features, especially in overweight and obese patients, should alert the physician towards the possibility of having PCOS.
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2. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu R. Prevalence of polycystic ovarian syndrome in Indian adolescents. J Pediatr Adolesc Gynecol. 2011;24(4):223–7.
3. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9.
4. Franks S, Gharani N, McCarthy M. Candidate genes in polycystic ovary syndrome. Hum Reprod Update. 2001;7(4):405–10.
5. Elsenbruch S, Hahn S, Kowalsky D, Öffner AH, Schedlowski M, Mann K, et al. Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(12):5801–7.
6. ESHRE TR, Group A-SPCW. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25.
7. Gowri BV, Chandravathi PL, Sindhu PS, Naidu KS. Correlation of skin changes with hormonal changes in polycystic ovarian syndrome: A cross-sectional study clinical study. Indian J Dermatol. 2015;60(4):419.
8. Clark C, Shalita A, Lowenstein E, Rudolph J, Glick S. The dermatologic manifestation of hyperandrogenism: A retrospective chart review: P1131. J Am Acad Dermatol. 2011;64(2).
9. Hong JS, Kwon HH, Park SY, Jung JY, Yoon JY, Min S, et al. Cutaneous manifestations of the subtypes of polycystic ovary syndrome in Korean patients. J Eur Acad Dermatol Venereol. 2015;29(1):42–7.
10. Feng J, Guo Y, Ma L, Xing J, Sun R, Zhu W. Prevalence of dermatologic manifestations and metabolic biomarkers in women with polycystic ovary syndrome in north China. J Cosmet Dermatol. 2018;17(3):511–7.
11. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):737–54.
12. Khomami MB, Tehrani FR, Hashemi S, Farahmand M, Azizi F. Of PCOS symptoms, hirsutism has the most significant impact on the quality of life of Iranian women. PLoS One. 2015;10(4):e0123608.
13. Bunker CB, NEWTON JA, KILBORN J, PATEL A, Conway GS, Jacobs HS, et al. Most women with acne have polycystic ovaries. Br J Dermatol. 1989;121(6):675–80.
14. Lee AT, Zane LT. Dermatologic manifestations of polycystic ovary syndrome. Am J Clin Dermatol. 2007;8(4):201–19.
15. Essah PA, Wickham III EP, Nunley JR, Nestler JE. Dermatology of androgen-related disorders. Clin Dermatol. 2006;24(4):289–98.
16. Williamson K, Gunn AJ, Johnson N, Milsom SR. The impact of ethnicity on the presentation of polycystic ovarian syndrome. Aust N Z J Obstet Gynaecol. 2001;41(2):202–6.
17. Huang Z, Yong E-L. Ethnic differences: Is there an Asian phenotype for polycystic ovarian syndrome? Best Pract Res Clin Obstet Gynaecol. 2016;37:46–55.
18. Hayashi N, Akamatsu H, Kawashima M, Group AS. Establishment of grading criteria for acne severity. J Dermatol. 2008;35(5):255–60.
19. Lumezi BG, Berisha VL, Pupovci HL, Goçi A, Hajrushi AB. Grading of hirsutism based on the Ferriman-Gallwey scoring system in Kosovar women. Adv Dermatol Allergol Dermatol Alergol. 2018;35(6):631.
20. Gupta M, Mysore V. Classifications of patterned hair loss: a review. J Cutan Aesthetic Surg. 2016;9(1):3.
21. Plewig G, Jansen T. Seborrheic dermatitis. Fitzpatrick’s Dermatol Gen Med. 1999;1:1482–9.
22. Phiske MM. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239.
23. Chaudhari AP, Mazumdar K, Mehta PD. Anxiety, depression, and quality of life in women with polycystic ovarian syndrome. Indian J Psychol Med. 2018;40(3):239–46.
24. Singh A, Chaudhary RKP. Study of Cutaneous Manifestations of Polycystic Ovarian Syndrome. JMSCR. 2017;5(4):21177–82.
25. Schmidt TH, Khanijow K, Cedars MI, Huddleston H, Pasch L, Wang ET, et al. Cutaneous findings and systemic associations in women with polycystic ovary syndrome. JAMA Dermatol. 2016;152(4):391–8.
26. Jain P, Jain S, Singh A, Goel S. Pattern of dermatologic manifestations in polycystic ovarian disease cases from a tertiary care hospital. Int J Adv Med. 2018;5(1):197–201.
27. Yerram C, Rao GV, Kilaru KR. Study of cutaneous manifestations in patients with polycystic ovarian syndrome attending a tertiary care centre. Int J Res. 2019;5(3):481.
28. Khunger N, Kumar C. A clinico-epidemiological study of adult acne: is it different from adolescent acne? Indian J Dermatol Venereol Leprol. 2012;78(3):335.
29. Lumezi BG, Pupovci HL, Berisha VL, Goçi AU, Gerqari A. Acne in hirsute women. Adv Dermatol Allergol Dermatol Alergol. 2014;31(6):356.
30. Dreno B, Poli F. Epidemiology of acne. Dermatology. 2003;206(1):7.
31. El Akawi Z, Abdel Latif Nemr N, Razzak A, Al Aboosi M. Factors believed by Jordanian acne patients to affect their acne condition. EMHJ-East Mediterr Health J 12 6 840-846 2006. 2006;
32. Kopera D, Wehr E, Obermayer-Pietsch B. Endocrinology of hirsutism. Int J Trichology. 2010;2(1):30.
33. Nazir F, Tasleem H, Tasleem S, Sher Z, Waheed K. Polycystic ovaries in adolescent girls from Rawalpindi. JPMA-J Pak Med Assoc. 2011;61(10):960.
34. Gatee OB, Al Attia HM, Salama IA. Hirsutism in the United Arab Emirates: a hospital study. Postgrad Med J. 1996;72(845):168–71.
35. Al-Ruhaily AD, Malabu UH, Sulimani RA. Hirsutism in Saudi females of reproductive age: a hospital-based study. Ann Saudi Med. 2008;28(1):28–32.
36. Zreik RS, Nasrallah MP. The prevalence of endocrinopathies among Lebanese women presenting with hirsutism to an endocrine clinic. Leban Med J. 2014;103(1006):1–6.
37. Saxena P, Prakash A, Nigam A, Mishra A. Polycystic ovary syndrome: Is obesity a sine qua non? A clinical, hormonal, and metabolic assessment in relation to body mass index. Indian J Endocrinol Metab. 2012;16(6):996.
38. Olsen EA. Disorders of hair growth: diagnosis and treatment. McGraw-Hill; 2003.
39. Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. 1981;140(7):815–30.
40. Sachdeva S. Hirsutism: evaluation and treatment. Indian J Dermatol. 2010;55(1):3.
41. Simpson NB, Barth JH. Hair patterns: hirsuties and baldness. Dis Hair Scalp 3rd Edn Oxf Blackewell Sci. 1997;67–122.
42. Birch MP, Messenger JF, Messenger AG. Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol. 2001;144(2):297–304.
43. Ozdemir S, Ozdemir M, Görkemli H, Kiyici A, Bodur S. Specific dermatologic features of the polycystic ovary syndrome and its association with biochemical markers of the metabolic syndrome and hyperandrogenism. Acta Obstet Gynecol Scand. 2010;89(2):199.
44. Keen MA, Shah IH, Sheikh G. Cutaneous manifestations of polycystic ovary syndrome: A cross-sectional clinical study. Indian Dermatol Online J. 2017;8(2):104.
45. Ramos PM, Miot HA. Female pattern hair loss: a clinical and pathophysiological review. An Bras Dermatol. 2015;90(4):529–43.
46. Hud JA, Cohen JB, Wagner JM, Cruz PD. Prevalence and significance of acanthosis nigricans in an adult obese population. Arch Dermatol. 1992;128(7):941–4.
47. PASQUALI R, ANTENUCCI D, CASIMIRRI F, VENTUROLI S, PARADISI R, FABBRI R, et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab. 1989;68(1):173–9.
48. Shivaprakash G, Basu A, Ashwin Kamath PS, Prabha Adhikari RU, Gopalakrishna HN. Acanthosis nigricansin PCOS patients and its relation with type 2 diabetes mellitus and body mass at a tertiary care hospital in southern India. J Clin Diagn Res JCDR. 2013;7(2):317.
49. Sharquie KE, Al-Bayatti A, Al-Bahar AJ, Al-Zaidi Q. Acanthosis nigricans as skin manifestation of polycystic ovaries syndrome in primary infertile females. 2004;
50. Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(6):618–37.
51. Pasquali R. The endocrine impact of obesity in eumenorrheic women. Androg Excess Disord Women Phila PA Lippincott-Raven. 1997;455–61.
52. McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson CA, Helm KD, et al. Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre-and early pubertal obese girls. J Clin Endocrinol Metab. 2007;92(2):430–6.
53. Day F, Karaderi T, Jones MR, Meun C, He C, Drong A, et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet. 2018;14(12):e1007813.
54. Dumitrescu R, Mehedintu C, Briceag I, Purcarea VL, Hudita D. The polycystic ovary syndrome: an update on metabolic and hormonal mechanisms. J Med Life. 2015;8(2):142.
55. Franik G, Bizoń A, Włoch S, Kowalczyk K, Biernacka-Bartnik A, Madej P. Hormonal and metabolic aspects of acne vulgaris in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci Internet. 2018;4411–8.
56. Cela E, Robertson C, Rush K, Kousta E, White DM, Wilson H, et al. Prevalence of polycystic ovaries in women with androgenic alopecia. Eur J Endocrinol. 2003;149(5):439–42.
57. Quinn M, Shinkai K, Pasch L, Kuzmich L, Cedars M, Huddleston H. Prevalence of androgenic alopecia in patients with polycystic ovary syndrome and characterization of associated clinical and biochemical features. Fertil Steril. 2014;101(4):1129–34.
2. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu R. Prevalence of polycystic ovarian syndrome in Indian adolescents. J Pediatr Adolesc Gynecol. 2011;24(4):223–7.
3. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9.
4. Franks S, Gharani N, McCarthy M. Candidate genes in polycystic ovary syndrome. Hum Reprod Update. 2001;7(4):405–10.
5. Elsenbruch S, Hahn S, Kowalsky D, Öffner AH, Schedlowski M, Mann K, et al. Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(12):5801–7.
6. ESHRE TR, Group A-SPCW. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25.
7. Gowri BV, Chandravathi PL, Sindhu PS, Naidu KS. Correlation of skin changes with hormonal changes in polycystic ovarian syndrome: A cross-sectional study clinical study. Indian J Dermatol. 2015;60(4):419.
8. Clark C, Shalita A, Lowenstein E, Rudolph J, Glick S. The dermatologic manifestation of hyperandrogenism: A retrospective chart review: P1131. J Am Acad Dermatol. 2011;64(2).
9. Hong JS, Kwon HH, Park SY, Jung JY, Yoon JY, Min S, et al. Cutaneous manifestations of the subtypes of polycystic ovary syndrome in Korean patients. J Eur Acad Dermatol Venereol. 2015;29(1):42–7.
10. Feng J, Guo Y, Ma L, Xing J, Sun R, Zhu W. Prevalence of dermatologic manifestations and metabolic biomarkers in women with polycystic ovary syndrome in north China. J Cosmet Dermatol. 2018;17(3):511–7.
11. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):737–54.
12. Khomami MB, Tehrani FR, Hashemi S, Farahmand M, Azizi F. Of PCOS symptoms, hirsutism has the most significant impact on the quality of life of Iranian women. PLoS One. 2015;10(4):e0123608.
13. Bunker CB, NEWTON JA, KILBORN J, PATEL A, Conway GS, Jacobs HS, et al. Most women with acne have polycystic ovaries. Br J Dermatol. 1989;121(6):675–80.
14. Lee AT, Zane LT. Dermatologic manifestations of polycystic ovary syndrome. Am J Clin Dermatol. 2007;8(4):201–19.
15. Essah PA, Wickham III EP, Nunley JR, Nestler JE. Dermatology of androgen-related disorders. Clin Dermatol. 2006;24(4):289–98.
16. Williamson K, Gunn AJ, Johnson N, Milsom SR. The impact of ethnicity on the presentation of polycystic ovarian syndrome. Aust N Z J Obstet Gynaecol. 2001;41(2):202–6.
17. Huang Z, Yong E-L. Ethnic differences: Is there an Asian phenotype for polycystic ovarian syndrome? Best Pract Res Clin Obstet Gynaecol. 2016;37:46–55.
18. Hayashi N, Akamatsu H, Kawashima M, Group AS. Establishment of grading criteria for acne severity. J Dermatol. 2008;35(5):255–60.
19. Lumezi BG, Berisha VL, Pupovci HL, Goçi A, Hajrushi AB. Grading of hirsutism based on the Ferriman-Gallwey scoring system in Kosovar women. Adv Dermatol Allergol Dermatol Alergol. 2018;35(6):631.
20. Gupta M, Mysore V. Classifications of patterned hair loss: a review. J Cutan Aesthetic Surg. 2016;9(1):3.
21. Plewig G, Jansen T. Seborrheic dermatitis. Fitzpatrick’s Dermatol Gen Med. 1999;1:1482–9.
22. Phiske MM. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239.
23. Chaudhari AP, Mazumdar K, Mehta PD. Anxiety, depression, and quality of life in women with polycystic ovarian syndrome. Indian J Psychol Med. 2018;40(3):239–46.
24. Singh A, Chaudhary RKP. Study of Cutaneous Manifestations of Polycystic Ovarian Syndrome. JMSCR. 2017;5(4):21177–82.
25. Schmidt TH, Khanijow K, Cedars MI, Huddleston H, Pasch L, Wang ET, et al. Cutaneous findings and systemic associations in women with polycystic ovary syndrome. JAMA Dermatol. 2016;152(4):391–8.
26. Jain P, Jain S, Singh A, Goel S. Pattern of dermatologic manifestations in polycystic ovarian disease cases from a tertiary care hospital. Int J Adv Med. 2018;5(1):197–201.
27. Yerram C, Rao GV, Kilaru KR. Study of cutaneous manifestations in patients with polycystic ovarian syndrome attending a tertiary care centre. Int J Res. 2019;5(3):481.
28. Khunger N, Kumar C. A clinico-epidemiological study of adult acne: is it different from adolescent acne? Indian J Dermatol Venereol Leprol. 2012;78(3):335.
29. Lumezi BG, Pupovci HL, Berisha VL, Goçi AU, Gerqari A. Acne in hirsute women. Adv Dermatol Allergol Dermatol Alergol. 2014;31(6):356.
30. Dreno B, Poli F. Epidemiology of acne. Dermatology. 2003;206(1):7.
31. El Akawi Z, Abdel Latif Nemr N, Razzak A, Al Aboosi M. Factors believed by Jordanian acne patients to affect their acne condition. EMHJ-East Mediterr Health J 12 6 840-846 2006. 2006;
32. Kopera D, Wehr E, Obermayer-Pietsch B. Endocrinology of hirsutism. Int J Trichology. 2010;2(1):30.
33. Nazir F, Tasleem H, Tasleem S, Sher Z, Waheed K. Polycystic ovaries in adolescent girls from Rawalpindi. JPMA-J Pak Med Assoc. 2011;61(10):960.
34. Gatee OB, Al Attia HM, Salama IA. Hirsutism in the United Arab Emirates: a hospital study. Postgrad Med J. 1996;72(845):168–71.
35. Al-Ruhaily AD, Malabu UH, Sulimani RA. Hirsutism in Saudi females of reproductive age: a hospital-based study. Ann Saudi Med. 2008;28(1):28–32.
36. Zreik RS, Nasrallah MP. The prevalence of endocrinopathies among Lebanese women presenting with hirsutism to an endocrine clinic. Leban Med J. 2014;103(1006):1–6.
37. Saxena P, Prakash A, Nigam A, Mishra A. Polycystic ovary syndrome: Is obesity a sine qua non? A clinical, hormonal, and metabolic assessment in relation to body mass index. Indian J Endocrinol Metab. 2012;16(6):996.
38. Olsen EA. Disorders of hair growth: diagnosis and treatment. McGraw-Hill; 2003.
39. Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. 1981;140(7):815–30.
40. Sachdeva S. Hirsutism: evaluation and treatment. Indian J Dermatol. 2010;55(1):3.
41. Simpson NB, Barth JH. Hair patterns: hirsuties and baldness. Dis Hair Scalp 3rd Edn Oxf Blackewell Sci. 1997;67–122.
42. Birch MP, Messenger JF, Messenger AG. Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol. 2001;144(2):297–304.
43. Ozdemir S, Ozdemir M, Görkemli H, Kiyici A, Bodur S. Specific dermatologic features of the polycystic ovary syndrome and its association with biochemical markers of the metabolic syndrome and hyperandrogenism. Acta Obstet Gynecol Scand. 2010;89(2):199.
44. Keen MA, Shah IH, Sheikh G. Cutaneous manifestations of polycystic ovary syndrome: A cross-sectional clinical study. Indian Dermatol Online J. 2017;8(2):104.
45. Ramos PM, Miot HA. Female pattern hair loss: a clinical and pathophysiological review. An Bras Dermatol. 2015;90(4):529–43.
46. Hud JA, Cohen JB, Wagner JM, Cruz PD. Prevalence and significance of acanthosis nigricans in an adult obese population. Arch Dermatol. 1992;128(7):941–4.
47. PASQUALI R, ANTENUCCI D, CASIMIRRI F, VENTUROLI S, PARADISI R, FABBRI R, et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab. 1989;68(1):173–9.
48. Shivaprakash G, Basu A, Ashwin Kamath PS, Prabha Adhikari RU, Gopalakrishna HN. Acanthosis nigricansin PCOS patients and its relation with type 2 diabetes mellitus and body mass at a tertiary care hospital in southern India. J Clin Diagn Res JCDR. 2013;7(2):317.
49. Sharquie KE, Al-Bayatti A, Al-Bahar AJ, Al-Zaidi Q. Acanthosis nigricans as skin manifestation of polycystic ovaries syndrome in primary infertile females. 2004;
50. Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(6):618–37.
51. Pasquali R. The endocrine impact of obesity in eumenorrheic women. Androg Excess Disord Women Phila PA Lippincott-Raven. 1997;455–61.
52. McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson CA, Helm KD, et al. Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre-and early pubertal obese girls. J Clin Endocrinol Metab. 2007;92(2):430–6.
53. Day F, Karaderi T, Jones MR, Meun C, He C, Drong A, et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet. 2018;14(12):e1007813.
54. Dumitrescu R, Mehedintu C, Briceag I, Purcarea VL, Hudita D. The polycystic ovary syndrome: an update on metabolic and hormonal mechanisms. J Med Life. 2015;8(2):142.
55. Franik G, Bizoń A, Włoch S, Kowalczyk K, Biernacka-Bartnik A, Madej P. Hormonal and metabolic aspects of acne vulgaris in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci Internet. 2018;4411–8.
56. Cela E, Robertson C, Rush K, Kousta E, White DM, Wilson H, et al. Prevalence of polycystic ovaries in women with androgenic alopecia. Eur J Endocrinol. 2003;149(5):439–42.
57. Quinn M, Shinkai K, Pasch L, Kuzmich L, Cedars M, Huddleston H. Prevalence of androgenic alopecia in patients with polycystic ovary syndrome and characterization of associated clinical and biochemical features. Fertil Steril. 2014;101(4):1129–34.
Abusailik, M. A. ., Muhanna, A. M., Almuhisen, A. A. ., Alhasanat, A. M. ., Alshamaseen, A. M., Bani Mustafa, S. M., & Nawaiseh, M. B. . (2021). Cutaneous manifestation of polycystic ovary syndrome. Dermatology Reports, 13(2). https://doi.org/10.4081/dr.2021.8799
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