İzotretinoinin Serum Hormonları ve Menstrüel Siklus Üzerine Etkileri

Öz

Amaç: Akne vulgaris tanısıyla izotretinoin tedavisi kullanan kadın hastaların serum hormon ve menstrüel sikluslarında ortaya çıkan değişikliklerin araştırılması amaçlanmıştır.

Gereç ve Yöntemler: Retrospektif olarak yapılan bu çalışmada, akne vulgaris nedeniyle izotretinoin tedavisi başlanmış, tedavi öncesi düzenli menstrüel sikluslara sahip, laboratuvar parametreleri normal sınırlarda olan, herhangi bir sistemik hastalığı bulunmayan ve başka ilaç kullanmayan kadın hastaların verileri incelenmiştir.

Bulgular: Çalışmaya dahil edilen 21 hastanın yaş ortalaması 22±3.87 idi. Hastalara uygulanan izotretinoin kümülatif dozu 123.90±4.71 mg/kg idi. Tedavi sırasında hastaların %19.1’inde dehidroepiandrosteron sülfat (DHEAS), %23.8’inde serbest testosteron (sT), %33.3’ünde total testosteron (tT) serum seviyelerinin referans aralığının üzerine çıktığı tespit edildi. Ortalama DHEAS ve sT düzeylerinde tedavi öncesine kıyasla istatistiksel olarak anlamlı olmayan artış saptandı (p>0.05). Tedavi boyunca normal sınırlar arasında ortalama tiroid stimüle edici hormon (TSH) değerlerinde istatistiksel olarak anlamlı (p<0.05) ve ortalama serbest T3 (sT3) düzeylerinde anlamlı olmayan (p>0.05) progresif azalma tespit edildi. Prolaktin, 17-hidroksiprogesteron, tT, folikül stimüle edici hormon, lüteinize edici hormon ve serbest T4 ortalama değerlerinde anlamlı bir fark bulunmadı (p>0.05). Hastaların %23.8'inde menstrüel düzensizlik olduğu saptandı. Bir hastada polimenore, bir hastada hipomenore, üç hastada oligomenore ve oligomenore gelişen hastaların birinde de siklus ortası kanama ortaya çıktığı tespit edildi. Menstrüel düzensizlik gelişen hastaların hormon değerlerinde herhangi bir değişiklik olmadığı belirlendi.

Sonuç: Bu çalışma izotretinoinin androjen metaboliması, tiroid hormonları ve menstrüel sikluslar üzerinde etkili olduğunu göstermektedir. Bu nedenle uzun süreli tedavilerde hiperandrojenizm ve hipotiroidi açısından takip önerilmektedir. Anormal uterin kanamaların hormonal kaynaklı olmadığı düşünülmektedir. Bu etkilerin hangi mekanizmalarla ortaya çıktığının kanıtlanabilmesi için ileri seviyede araştırmalara gerek vardır.

Anahtar Kelimeler

• Akne vulgaris,izotretinoin,serum hormonları,menstrüel siklus

The Effects of Isotretinoin on Menstrual Cycle and Hormone Levels

Öz

Introductıon: This study aimed at examining the effects of isotretinoin treatment on menstrual cycle and serum hormones in women with acne vulgaris.

Materials and methods: In this retrospective study, the data of female patients who have been treated with isotretinoin for acne vulgaris, had regular menstrual cycles before treatment, had normal laboratory parameters, had no any systemic disease and did not take any medicine have been examined.

Results: The mean age of the 21 women included in the study was 22±3.87. The cumulative dose of isotretinoin administered to the patient was 123.90±4.71 mg/kg. During the treatment, in 19.1% of the patients dehydroepiandrosterone sulfate (DHEAS), in 23.8% of free testosterone (fT) and in 33.3% of total testosterone (tT) were reported to be higher than the reference range of serum levels. There was a statistically insignificant increase in mean DHEAS and fT levels (p>0.05) compared to before treatment. During the treatment, a statistically significant in mean thyroid stimulating hormone (TSH) values (p<0.05) and a insignificant in mean free T3 (fT3) values (p>0.05) was determined progressive decrease between normal limits. There was no significant difference in mean values of 17-hydroxyprogesterone, tT, prolactin, follicle stimulating hormone, luteinizing hormone and free T4 (p>0.05). We found that 23.8% of the patients had menstrual irregularity. In one patient polymenorrhea was observed and hypomenorrhea in another one. Also, oligomenorrhea was observed in three patient, with one of them hemorrhage in the middle of her cycle. It has been determined that there is no change in the hormone levels of patients with menstrual irregularity.

Conclusion: In this study show that isotretinoin has an effect on androgen metabolism, on thyroid hormones and on menstrual cycles. For this reason, we recommend follow-up in terms of hyperandrogenism and hypothyroidism in long-term treatment. As a result of the data, it can be said that abnormal uterine bleeding is not hormonal origin. Further studies are needed to prove what kind of mechanism cause these effects.

Anahtar Kelimeler

• Acne vulgaris,isotretinoin,serum hormones,menstrual cycle

Kaynakça

1. Katsambas A, Papakonstantinou A. Papakonstantinou A. Acne: Systemic treatment. Clin Dermatol. 2004;22(5):412-8.
2. Saurat JH. Oral isotretinoin. Where now, where next? Dermatology. 1997;195(Suppl 1):13.
3. Törmä H. Interaction of isotretinoin with endogenous retinoids. J Am Acad Dermatol. 2001;45(5):S143-9.
4. Lookingbill DP, Demers LM, Tigelaar RE, Shalita AR. Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne. Arch Dermatol .1988;124(4):540-3.
5. Marsden JR, Trinick TR, Laker MF, Shuster S. Effects of isotretinoin on serum lipids and lipoproteins, liver and thyroid function. Clin Chim Acta. 1984;143(3):243-51.
6. Hickey M, Balen A. Menstrual disorders in adolescence: Investigation and management. Hum Reprod Update. 2003;9(5):493-504.
7. Bruno NP, Beacham BE, Burnett JW. Adverse effects of isotretinoin therapy. Cutis. 1984;33(5):484-9.
8. Edwards L, Alberts DS, Levine N. Clinical toxicity of low-dose isotretinoin. Cancer Treatment Reports. 1986;70(5):663-4.

9. Cox NH. Amenorrhoea during treatment with isotretinoin. Br J Dermatol 1988;118(6):857-8.
10. Karlsson T, Vahlquist A, Kedishvili N, Törmä H. 13-cis-Retinoic acid competitively inhibits 3α-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands? Biochem Biophys Res Commun. 2003;303(1):273-8.
11. Biswas MG, Russell DW. Expression cloning and characterization of oxidative 17β- and 3α-hydroxysteroid dehydrogenases from rat and human prostate. J Biol Chem. 1997; 272(25):15959-15966.
12. Karadag AS, Takci Z, Ertugrul DT, Bilgili SG, Balahoroglu R, Takir M. The effect of different doses of isotretinoin on pituitary hormones Dermatology. 2015;230(4):354-35
13. O’Leary TJ, Simo IE, Kanigsberg ND, Ooi TC. Lack of effect of isotretinoin on thyroid-function tests. Clin Chem. 1986;32(5):913-4.
14. Uyar B, Solak A, Saklamaz A, Akyildiz M, Genc B, Gökduman A. Effects of isotretinoin on the thyroid gland and thyroid function tests in acne patients: A preliminary study. Indian J Dermatol Venereol Leprol. 2016;82(5):587-8.
15. N Yıldırım, S Doğan, N Atakan. Evaluation of thyroid function tests of acne vulgaris patients treated with systemic isotretinoin. Journal of Dermatolog Treat. 2017;28(2):141-4.
16. Karadag AS, Ertugrul DT, Tutal E, Akin KO. Isotretinoin influences pituitary hormone levels in acne patients. Acta Derm Venereol. 2011;91(1):31-4.
17. Dianne Deplewski D, Rosenfield R. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000;21(4):363-92.
18. Brown NS, Smart A, Sharma V, et al. Thyroid hormone resistance and increased metabolic rate in the RXR-γ –deficient mouse. J Clin Invest. 2000;106(1):73-79
19. Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001;81(3):1097-142.
20. Li D, Li T, Wang F, Tian H, Samuels HH. Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer. Mol Cell Biol. 2002;22(16):5782-92.
21. Liu S, Ogilvie KM, Klausing K, et al. Mechanism of selective retinoid X receptor agonist-induced hypothyroidism in the rat. Endocrinology. 2002;143(8):2880-5.
22. Christmas T. Roaccutane and menorrhagia. J Am Acad Dermatol. 1988;18(3):576-7.
23. Demirci GT, Mertoğlu E, Altunay İK, Atış G, Küçükünal A. The investigation of the frequency of menstrual irregularity and hypertrichosis due to isotretinoine usage in female patients. Turk Arch Dermatol Venereology. 2014;48(3):152-155.
24. Karadag AS, Çalka Ö, Akdeniz A. Evaluation of side effects of isotretinoin in 150 patients with acne vulgaris. Turk Arch Dermatol Venereology. 2011;45(1):37-42
25. Halkier-Sorensen L. Menstrual changes in a patient treated with etretinate. Lancet. 1987;2(8559):636.
26. Lithgow DM, Poliztzer WM. Vitamin A in treatment of menorrhagia. S Afr Med J. 1977;51(7):191-3.
27. Loughney AD, Redfern CP. Menstrual cycle related differences in the proliferative responses of cultured human endometrial stromal cells to retinoic acid. J Reprod Fertil. 1995;105(1):153-9.
28. Fukunaka K, Saito T, Wataba K, Ashihara K, Ito E, Kudo R. Changes in expression and subcellular localization of nuclear retinoic acid receptors in human endometrial epithelium during the menstrual cycle. Mol Hum Reprod. 2001;7(5):437-446.
29. Carter CA, Parham GP. State of differentiation affects the response of endometrial adenocarcinoma cells to retinoic acid. Anticancer Res. 1997;17(3C):1973-83.
30. Kudelka AP, Freedman RS, Edwards CL, et al. Metastatic adenocarcinoma of the endometrium treated with 13-cis-retinoic acid plus interferon-alpha. Anticancer Drugs. 1993;4(3):335-7.