항암화학요법을 받는 혈액암 환자에서 조기난소기능부족증 예방을 위한 성선자극호르몬분비호르몬작용제의 병합 사용
GnRH Agonist Co-treatment for Prevention of Primary Ovarian Insufficiency in Patients with Hematologic Malignancies Undergoing Chemotherapy
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
연구목적: 혈액암으로 진단 받고 항암화학요법을 시행 받는 환자에서 난소 기능 보존을 위한 성선자극분비호르몬작용제 병합요법의 효과를 분석하고자 하였다. 연구재료 및 방법: 2010년 3월부터 2012년 2월까지 대학병원에서 혈액암으로 처음 진단 받고 항암화학요법을 시행 받은 폐경 전 젊은 여성을 연구 대상에 포함하였다. 결과: 29명 (15-39세)의 환자가 연구 대상에 포함되었으며, 이 중 5명은 항암화학요법 중 leuprolide를 병합투여 받았고 24명은 항암화학요법만 시행 받았다. 항암화학요법만 단독으로 시행 받은 24명 중에서 17명이 치료 종료 1년 이내 조기난소기능부족증으로 진단 받았으며 leuprolide 병합 투여군 5명 중에서는 1명만 치료 종료 1년 이내 조기난소기능부족증으로 진단 받았으나, 두 군간 통계적으로 유의한 차이는 보이지 않았다 (P = 0.054). Leuprolide 병합 투여군에서 혈청 항뮐러리안호르몬 농도는 치료 전 (5.57 ± 0.18 ng/mL)에 비해 치료 후 (1.84 ± 0.22 ng/mL) 유의한 감소를 보였다 (P < 0.001). 결론: 성선자극분비호르몬작용제는 조기폐경 예방을 위해 유용한 방법이 될 수 있으나 아직까지 그 효과는 논란의 여지가 있다. 향후 충분한 추적관찰 기간을 가지는 대규모의 다기관 전향적 연구가 필요할 것으로 생각된다.
Abstract
Objectives: The aim of this study was to assess the effect of gonadotropin-releasing hormone (GnRH) agonist co-treatment for gonadal protection in patients with hematologic neoplasms undergoing chemotherapy. Methods: Young premenopausal women who were diagnosed with leukemia or lymphoma between March 2010 and February 2012 and undergoing chemotherapy in a university hospital were included in this study. Results: Twenty-nine patients aged 15‒39 years participated in this study. Among the patients, five patients were receiving leuprolide concomitant with chemotherapy, and twenty-four patients were receiving chemotherapy alone. Seventeen patients in the chemotherapy alone group stopped menstrating and were diagnosed with primary ovarian insufficiency (POI) within one year after chemotherapy; and only one patient had POI in the chemotherapy plus leuprolide group, but these differences were not statistically significant (P = 0.054). In the chemotherapy plus leuprolide group, serum anti-müllerian hormone (AMH) levels were significantly lower than basal serum AMH levels (5.57 ± 0.18 ng/mL) (P < 0.001) after treatment (1.84 ± 0.22 ng/mL). Conclusion: GnRH agonist may be a promising option for the prevention of POF, but the effectiveness of GnRH agonist is still debatable. A large prospective multi-center trial with adequate follow-up is needed.
참고문헌 (32)
- Goswami D, "Premature ovarian failure", Hum Reprod Update, 11, pp.391~410 (2005)
- The North American Menopause Society, "Estrogen and progestogen use in postmenopausal women: 2010 position statement of The North American Menopause Society", Menopause, 17, pp.242~255 (2010)
- Sturdee DW, "Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health", Climacteric, 14, pp.302~320 (2011)
- Taylor AE, "Systemic adversities of ovarian failure", J Soc Gynecol Investig, 8, pp.S7~S9 (2011)
- Kalantaridou SN, "Premature ovarian failure", Endocrinol Metab Clin North Am, 27, pp.989~1006 (1998)
- Snowdon DA, "Is early natural menopause a biologic marker of health and aging", Am J Public Health, 79, pp.709~714 (1989)
- Falcone T, "Ovarian function preservation in the cancer patient", Fertil Steril, 81, pp.243~257 (2004)
- Jemal A, "Cancer statistics", CA Cancer J Clin, 56, pp.106~130 (2006)
- 이정렬, "여성암 생존자에서의 가임력 보존", Obstetrics & Gynecology Science, 51(8), pp.820~834 (2008), 대한산부인과학회
- Blumenfeld Z., "How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embryo, oocytes, or ovaries", Oncologist, 12, pp.1044~1054 (2007)
- Blumenfeld Z, "Gender difference: fertility preservation in young women but not in men exposed to gonadotoxic chemotherapy", Minerva Endocrinol, 32, pp.23~34 (2007)
- Ataya KM, "A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats", Cancer Res, 45, pp.3651~3656 (1985)
- Ataya KM, "Gonadotropin-releasing hormone agonist inhibits physiologic ovarian follicular loss in rats", Acta Endocrinol, 121, pp.55~60 (1989)
- Ataya KM, "Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide- induced ovarian follicular depletion in rhesus monkeys", Biol Reprod, 52, pp.365~372 (1995)
- Tangir J, "Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary", Obstet Gynecol, 101, pp.251~257 (2003)
- Blumenfeld Z, "Ovarian cryopreservation versus ovarian suppression by GnRH analogues: primum non nocere", Hum Reprod, 19, pp.1924~1925 (2004)
- Beck-Fruchter R, "GnRH agonist therapy as ovarian protectants in female patients undergoing chemotherapy: a review of the clinical data", Hum Reprod Update, 14, pp.553~561 (2008)
- Waxman JH, "Failure to preserve fertility in patients with Hodgkin’s disease", Cancer Chemother Pharmacol, 19, pp.159~162 (1987)
- Oktay K, "Absence of conclusive evidence for the safety and efficacy of gonadotropin-releasing hormone analogue treatment in protecting against chemotherapy-induced gonadal injury", Oncologist, 12, pp.1055~1066 (2007)
- Kim TH, "Non-vertebral Fractures due to Recurrent Falls after Premature Menopause", J Korean Soc Menopause, 16, pp.52~54 (2010)
- Parker WH, "Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study", Obstet Gynecol, 113, pp.1027~1037 (2009)
- The North American Menopause Society, "The 2012 Hormone Therapy Position Statement of The North American Menopause Society", Menopause, 19, pp.257~271 (2012)
- Blumenfeld Z, "GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy", Hum Reprod Update, 14, pp.543~552 (2008)
- Badawy A, "Gonadotropin- releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study", Fertil Steril, 91, pp.694~697 (2009)
- Kim SS, "Use of hormonal protection for chemotherapy-induced gonadotoxicity.", Clin Obstet Gynecol, 53, pp.740~752 (2010)
- Meduri G, "Delayed puberty and primary amenorrhea associated with a novel mutation of the human folliclestimulating hormone receptor: clinical, histological, and molecular studies", J Clin Endocrinol Metab, 88, pp.3491~3498 (2003)
- Gerber B, "Effect of luteinizing hormonereleasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study", J Clin Oncol, 29, pp.2334~2341 (2011)
- Meirow D, "Reproduction post-chemotherapy in young cancer patients", Mol Cell Endocrinol, 169, pp.123~131 (2000)
- Del Mastro L, "Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapyinduced early menopause in premenopausal women with breast cancer: a randomized trial", JAMA, 306, pp.269~276 (2011)
- 이정렬, "여성 생식에서 Anti-Müllerian Hormone의 역할", Obstetrics & Gynecology Science, 52(3), pp.285~300 (2009), 대한산부인과학회
- Anderson RA, "The effects of chemotherapy and longterm gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer", Hum Reprod, 21, pp.2583~2592 (2006)
- van Beek RD, "Anti-Mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin’s lymphoma during Childhood", J Clin Endocrinol Metab, 92, pp.3869~3874 (2007)