PINAR SOLMAZ HASDEMİR, Hasan TERZİ, Semra Oruç KOLTAN

Hipogonadotropik Hipogonadizm Olgularına Yaklaşım: İnfertiliteTedavisi ve Uzun Dönem Yönetim

Amaç: GnRH veya gonadotropin yetmezliğine bağlı ortaya çıkan tablo Hipogonadotropik Hipogonadizm (HH) olarak adlandırılır. Bu derlemenin amacı, hipogonadotropik hipogonadizmin ortaya çıkış nedenleri, tanı ve tedavi prensiplerini irdelemektir. Gereç ve Yöntem: Bu derleme, PubMed ve Scopus bilgi toplama merkezlerine 'hipogonadotropik hipogonadizm, infertilite, anovulasyon' anahtar sözcükleri girilerek konu ile ilgili makalelerin toplanıp, elde edilen bilgilerin sistematik olarak özetlenmesi suretiyle elde edilmiştir. Bulgular: Hipogonadotropik Hipogonadizm' de hipotalamustan gonadotropin salıverici hormonda (GnRH) azalma veya GnRH uyarısına hipofizin yanıtsız kalması söz konusudur. Anovulasyon görülen kadınların %5-10' u bu gruba dahildir. Primer ve sekonder olarak iki gruba ayrılır. Primer HH' de genetik etiyoloji üzerinde durulmaktadır. HH olgularında uygun tanı ve gonadotropin destek tedavisi ile fertilite sağlanabilir. Sonuç: HH tipik olarak düşük veya uygunsuz gonadotropin seviyelerine bağlı olarak dolaşımdaki sex steroidlerinde düşüklükle karakterizedir. HH' in dikkatli ve erken tanısı olumsuz fiziksel ve psikolojik sekelleri ortadan kaldırarak normal kemik kitlesinin korunmasına ve fertilitenin restorasyonuna olanak tanır.

Approachto Hypogonadotropic Hypogonadism Cases: InfertilityTreatmentandLong-Term Management

Aim: Hypogonadotropic hypogonadism (HH) is a condition of GnRH or gonadotropin deficiency. The aim of this study was consideration of the reasons, mechanisms, diagnosis and management of HH. Material and Methods: The key words of 'hypogonadotropic hypogonadism, infertility and anovulation' entered to PubMed and Scopus database centers. The related articles summarized in this review. Results: HH is the situation of the lessens of the Gonadotropin Releasing Hormone (GnRH) release from hypothalamus or the inadequate response of the hypophys to the GnRH stimulation. HH comprises 5-10% of the anovulatory women. Two subgrupes defined as primary and secondary types. The genetic basis is important for the primary type. Fertility is possible with proper diagnosis and gonadotropin supportive treatment. Conclusion: HH is characterised by the low blood levels of sex steroids resulted from the low or improper levels of gonadotropins. Attentive and early diagnosis of HH could prevent the negative psychological and physical sequeles and facilitates the normal bone mass and the restoration of fertility

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1-Layman LC. The genetic basis of female reproductive disorders: etiology and clinical testing. Mol Cell Endocrinol. 2013;370:138-48.
2- Franco B, Guioli S, Pragliola A, et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature. 1991 Oct 10;353(6344):529-36.
3-Legouis R, Hardelin JP, Levilliers J, et al. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell. 1991;67: 423-35.
4-Koika V, Varnavas P, Valavani H, et al. Comparative functional analysis of two fibroblast growth factor receptor 1 (FGFR1) mutations affecting the same residue (R254W and R254Q) in isolated hypogonadotropic hypogonadism (IHH). Gene. 2013; 516: 146-51
5-Novo A, Guerra IC, Rocha F, et al. Kallmann syndrome in a female adolescent: a new mutation in the FGFR1 gene. BMJ Case Rep. 2012: 29;2012.
6-Mason AJ, Hayflick JS, Zoeller RT, et a. A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science. 1986; 234: 1366-71.
7-Nakayama Y, Wondisford FE, Lash RW, et al. Analysis of gonadotropin-releasing hormone gene structure in families with familial central precocious puberty and idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1990; 70:1233-8.
8-Layman LC, Cohen DP, Jin M, et al. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat Genet. 1998; 18:14-5.
9-de Roux N, Young J, Misrahi M, et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med. 1997; 337(22):1597-602.
10- Bhagavath B1, Layman LC. The genetics of hypogonadotropic hypogonadism. Semin Reprod Med. 2007; 25: 272-86.
11- Meysing AU, Kanasaki H, Bedecarrats GY, et al. GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropinreleasing hormone. J Clin Endocrinol Metab. 2004; 89(7):3189-98.
12- Tsutsumi R, Webster NJ. GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr J. 2009;56:729-37.
13- Martin KA, Hall JE, Adams JM, et al. Comparison of exogenous gonadotropins and pulsatile gonadotropin-releasing hormone for induction of ovulation in hypogonadotropic amenorrhea. J Clin Endocrinol Metab. 1993; 77:125-9.
14- Jansen RP. Pulsatile intravenous gonadotrophin releasing hormone for ovulation induction: determinants of follicular and luteal phase responses. Hum Reprod. 1993 Nov;8 Suppl 2:193-6.
15- Martin K, Santoro N, Hall J, et al. Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin-releasing hormone. J Clin Endocrinol Metab. 1990; 71:1081A-1081G. Filicori M, Flamigni C, Dellai P, et al. Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles. J Clin Endocrinol Metab. 1994; 79: 1215-20.
16- Burgués S; Spanish Collaborative Group on Female Hypogonadotrophic Hypogonadism. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain. Hum Reprod. 2001; 16:2525-32.
17- Ulug U, Ben-Shlomo I, Tosun S, et al. The reproductive performance of women with hypogonadotropic hypogonadism in an in vitro fertilization and embryo transfer program. J Assist Reprod Genet. 2005; 22:167-71.
18- Carone D, Caropreso C, Vitti A, et al. Efficacy of different gonadotropin combinations to support ovulation induction in WHO type I anovulation infertility: clinical evidences of human recombinant FSH/human recombinant LH in a 2:1 ratio and highly purified human menopausal gonadotropin stimulation protocols. J Endocrinol Invest. 2012; 35: 996-1002.
19- Milardi D, Giampietro A, Baldelli R, et al. Fertility and hypopituitarism. J Endocrinol Invest. 2008;31:71-4.
20- Hirshfeld-Cytron J, Kim HH. Treatment of infertility in women with pituitary tumors. Expert Rev Anticancer Ther. 2006; 6: S55-62.
21- Silveira LF1, Latronico AC. Approach to the patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013; 98:1781-8.