Hirsutizm ve D Vitamini
Özet
Hirsutizm, üreme çağındaki kadınların %5-25'ini etkileyen, androjene duyarlı bölgelerde vellus kıllarının terminal kıllara dönüşmesiyle karakterize önemli bir klinik tablodur. Genellikle polikistik over sendromuna (PKOS) sekonder gelişen bu durum, idiyopatik veya nadiren adrenal tümörler, Cushing sendromu ve ilaç kullanımı gibi nedenlerle de ortaya çıkabilmektedir. Tanısında en önemli parametre serbest androjen endeksi olup tedavi sürecinde oral kontraseptifler, antiandrojenler ve insülin duyarlaştırıcılar gibi ajanlar kullanılmaktadır. Literatürde, hirsutizm ve PKOS hastalarında D vitamini düzeylerinin sağlıklı kontrol gruplarına kıyasla belirgin şekilde düşük olduğu ve D vitamini eksikliğinin insülin direnci, metabolik sendrom ve kardiyovasküler hastalıklar gibi komorbiditelerle güçlü bağlantılar gösterdiği bildirilmiştir. D vitamini reseptörlerinin glikoz metabolizması ve testosteron düzeylerini regüle eden genlerle ilişkisi bu durumu moleküler düzeyde desteklemektedir. Yapılan replasman çalışmalarında, D vitamini takviyesinin insülin direnci, ovulatuvar siklus düzensizlikleri ve folliküler yanıt üzerinde olumlu etkiler sağladığı görülse de hirsutizm skoru ve hormonal profil üzerindeki klinik etkinliği hakkında literatürde çelişkili sonuçlar mevcuttur. Bu nedenle, hirsutizm tedavisinde D vitamini replasmanının net endikasyonlarını ve pozolojisini belirleyebilmek için daha geniş kapsamlı, randomize ve plasebo kontrollü klinik çalışmalara ihtiyaç duyulmaktadır.
Hirsutism is a significant clinical condition affecting 5-25% of reproductive-aged women, characterized by the transformation of vellus hair into terminal hair in androgen-sensitive areas. Commonly developing secondary to polycystic ovary syndrome (PCOS), this condition can also arise due to idiopathic reasons, or rarely from adrenal tumors, Cushing's syndrome, and medication use. The free androgen index is considered the most crucial parameter for its diagnosis, and agents such as oral contraceptives, antiandrogens, and insulin sensitizers are utilized during the treatment process. Literature indicates that vitamin D levels are significantly lower in patients with hirsutism and PCOS compared to healthy control groups, with vitamin D deficiency demonstrating robust links to comorbidities like insulin resistance, metabolic syndrome, and cardiovascular diseases. The relationship of vitamin D receptors with genes regulating glucose metabolism and testosterone levels supports this association at the molecular level. Although replacement studies demonstrate that vitamin D supplementation yields positive outcomes on insulin resistance, ovulatory cycle irregularities, and follicular response, conflicting results persist regarding its clinical efficacy on hirsutism scores and hormonal profiles. Consequently, extensive, randomized, and placebo-controlled clinical trials are strictly required to define the precise indications and dosage of vitamin D replacement in hirsutism management.
Referanslar
Wehr E, Pilz S, Schweighofer N, et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol. 2009;161:575-82.
Trummer C, Pilz S, Schwetz V, et al. Vitamin D, PCOS and androgens in men: A systematic review. Endocr Connect. 2018;7: R95-R113.
Pilz S, März W, Wellnitz B, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008;93:3927-35.
Lerchbaum E, Pilz S, Trummer C, et al. Serum vitamin D levels and hypogonadism in men. Andrology 2014;2:748-54.
Lerchbaum E, Rabe T. Vitamin D and female fertility. Curr Opin Obstet Gynecol. 2014;26:145-50.
Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med. 2005;353:2578-88.
Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Endocr Rev. 2000;21:347-62.
Messenger A. The control of hair growth: an overview. J Invest Dermatol. 1993;101:4-9S.
Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000;21:363-92.
Glintborg D, Andersen M. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol Endocrinol. 2010;26:281-96.
Hunter MH, Carek PJ. Evaluation and treatment of women with hirsutism. Am Fam Physician. 2003;67:2565-72.
Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91:456-88.
Hassa H, Mete Tanir H, Yildirim A, et al. The hirsutism scoring system should be population specific. Fertil Steril. 2005;84:778-80.
Moayeri H. A prospective study of etiologies of hirsutism and screening for non classic congenital adrenal hyperplasia due to 21 hyroxylase deficiency in 93 female adolescents. Acta Medica Iranica. 2000;38:238-9.
Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005;352:1223-.36.
Somani N, Turvy D. Hirsutism: an evidence based treatment update. Am J Clin Dermatol. 2014;15:247-66.
Loriaux DL. An Approach to the patient with hirsutism. J Clin Endocrinol Metab. 2012; 97:2957-68.
Liu K, Motan T, Claman P. No. 350- hirsutism: evaluation and treatment. J Obstet Gynaecol Can. 2017;39:1054-68.
Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004;89:453-62.
Yildiz BO. Diagnosis of hyperandrogenism: clinical criteria. Best Pract Res Clin Endocrinol Metab. 2006;20:167-76.
Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998;83:3078-82.
Tekin O, Isik B, Avci Z, et al. Hirsutism: common clinical problem or index of serious disease? MedGenMed. 2004;6:56.
Martin KA, Anderson RR, Chang RJ, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1233-57.
Samojlik E, Kirschner MA, Silber D, et al. Elevated production and metabolic clearance rates of androgens in morbidly obese women. J Clin Endocrinol Metab. 1984;59:949-54.
Kirschner MA, Samojlik E, Silber D. A comparison of androgen production and clearance in hirsute and obese women. J Steroid Biochem. 1983;19:607-14.
Matteri RK, Stanczyk FZ, Gentzschein EE, et al. Androgen sulfate and glucuronide conjugates in nonhirsute and hirsute women with polycystic ovarian syndrome. Am J Obstet Gynecol. 1989;161:1704-9.
O’Driscoll JB, Mamtora H, Higginson J et al. A prospective study of the prevalence of clearcut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia. Clin Endocrinol. 1994;41:231-6.
Sirmans S, Pate K. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1-13.
Kim JJ, Choi YM, Chae SJ, Hwang KR, Yoon SH, Kim MJ, et al. Vitamin D deficiency in women with polycystic ovary syndrome. Clin Exp Reprod Med. 2014;41:80-5.
Bonakdaran S, Khorasani ZM, Davachi B, Khorasani JM. The effects of calcitriol on improvement of insulin resistance, ovulation and comparison with metformin therapy in PCOS patients: a randomized placebo-controlled clinical trial. Iran J Reprod Med. 2012;10:465-72.
Stepto NK, Cassar S, Joham AE, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod. 2013;28:777-84.
Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab. 2006;91:2100-4.
Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16:347-63.
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;18:618-37.
Nikolaou D, Gilling-Smith C. Hirsutism. Cur Obstet Gynecol. 2005;15:174-82.
Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2012;77:343:50.
Li HW, Brereton RE, Anderson RA, et al. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism. 2011;60:1475-81.
Khan SH, Manzoor R, Shahid R, et al. Comparison of Vitamin D Status for Hirsutism, Biochemical Hyperandrogenism, Glycemia and Dyslipidemia among Subjects with Polycystic Ovarian Syndrome (PCOS). J Womens Health. 2019; Issues Care 8:4.
Khan H, Kunutsor S, Franco O, et al. Vitamin D, type 2 diabetes and other metabolic outcomes: a systematic review and meta-analysis of prospective studies. Proc Nutr Soc. 2013;72:89-97.
Song Y, Wang L, Pittas A, et al. Blood 25-hydroxy vitamin d levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2013;36:1422-8.
Krul-Poel Y, Snackey C, Louwers Y, et al. The role of vitamin D in metabolic disturbances in polycystic ovary syndrome: a systematic review. Eur J Endocrinol. 2013;169:853-65.
Pittas A, Lau J, Hu F, et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92:2017-29.
Holick M. Vitamin D deficiency. N Engl J Med. 2007;357:266-81.
Wehr E, Trummer O, Giuliani A, et al. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011;164:741-9.
Sirmans S, Pate K. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1-13.
Al-Bayyari N, Al-Domi H, Zayed F, et al. Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial. Clin Nutr. 2021;40:870-8.
Wehr E, Moller R, Horejsi R, et al. Subcutaneous adipose tissue topography and metabolic disturbances in polycystic ovary syndrome. Wien Klin Wochenschr. 2009;121:262-9.
Li HW, Brereton RE, Anderson RA, et al. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism. 2011;60:1475-81.
Lerchbaum E, Theiler-Schwetz V, Kollmann M, et al. Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial. Nutrients. 2021;13:547.
Hahn S, Haselhorst U, Tan S, et al. Low serum 25-hydroxyvitamin D concentrations are associated with insülin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2006;114:577-83.
Yildizhan R, Kurdoglu M, Adali E. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet. 2009;280:559-63.
Selimoglu H, Duran C, Kiyici S, et al. The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Invest. 2010;33:234-8.
Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest. 2011;34:757-63.
Rashidi B, Haghollahi F, Shariat M, Zayerii F. The effects of calcium-vitamin D and metformin on polycystic ovary syndrome: a pilot study. Taiwan J Obstet Gynecol. 2009;48:142-7.
Javed Z, Papageorgiou M, Deshmukh H, et al. A randomized, controlled trial of vitamin D supplementation on cardiovascular risk factors, hormones, and liver markers in women with polycystic ovary syndrome. Nutrients. 2019;11:188.
Savastano S, Barrea L, Savanelli MC, et al. Low vitamin D status and obesity: Role of nutritionist. Rev Endocr Metab Disord. 2017;18:215-25.
Barrea L, Frias-Toral E, Pugliese G, et al. Vitamin D in obesity and obesity-related diseases: An overview. Minerva Endocrinol (Torino). 2021;46:177-92.
Stewart PM, Shackleton CH, Beastall GH, et al. 5 alpha-reductase activity in polycystic ovary syndrome. Lancet. 1990;335:431-3.
Lanzone A, Villa P, Fulghesu AM, et al. The growth hormone response to growth hormone-releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia. Hum Reprod. 1995;10:1653-7.
Dagogo-Jack S, al Ali N, Qurttom M. Augmentation of bone mineral density in hirsute women. J Clin Endocrinol Metab. 1997;82:2821-5.
Yuksel O, Dokmetas HS, Topcu S, et al. Relationship between bone mineral density and insülin resistance in polycystic ovary syndrome. J Bone Miner Metab. 2001;19:257-62.
Dixon JE, Rodin A, Murby B, et al. Bone mass in hirsute women with androgen excess. Clin Endocrinol (Oxf). 1989;30:271-7.
Good C, Tulchinsky M, Mauger D, et al. Bone mineral density and body composition in lean women with polycystic ovary syndrome. Fertil Steril. 1999;72:21-5.
Gregoriou O, Kouskouni E, Bakas P et al. Bone mineral density in women with idiopathic hirsutism. Gynecol Endocrinol. 2000;14:364-8.
Kirchengast S, Huber J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod. 2001;16:1255-60.
Adami S, Zamberlan N, Castello R, et al. Effect of hyperandrogenism and menstrual cycle abnormalities on bone mass and bone turnover in young women. Clin. Endocrinol (Oxf). 1998;48:169-73.
Glintborg D, Andersen M, Hagen C, Hermann AP. Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism. Clin Endocrinol (Oxf). 2005;62:683-91.
Noyan V, Yucel A, Sagsoz N. The association of bone mineral density with insulin resistance in patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2004;115:200-5.
Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999;84:165-9.
Firouzabadi R, Aflatoonian A, Modarresi S, et al. Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complement Ther Clin Pract. 2012;18:85-8.
