Correspondence The treatment of menorrhagia in female stem cell transplant recipients Bone Marrow Transplantation (2005) 35, 827. doi:10.1038/sj.bmt.1704890 Published online 7 March 2005 We read with interest the paper from Amsterdam et al 1 recently published in this journal. We are pleased to share with the authors the importance of what is normally considered a not very stringent issue after stem cell transplantation, but we do not agree with the statement proposed by the authors. First of all the definition of menorrhagia may vary from mild to severe or intractable; therefore, the approach may vary from supportive mea- sures to emergency measures including high-dose oral contraceptives or i.v. conjugated estrogens or even surgery. We do not hold, in fact, that menorrhagia should always be treated aggressively. Conjugated estrogens and oral contra- ceptives are known to increase liver toxicity after stem cell transplantation, producing an increase in the frequency of veno-occlusive disease, which was statistically significant when lynesterol or norethisterone were routinely adopted after stem cell transplantation. 2–5 Obviously, this increase was observed mainly after allogeneic stem cell transplant- ation. In the series reported by Amsterdam et al, the patients included in the study were mainly recipients of allogeneic transplantation. Since hormonal treatment is significantly associated with an increased risk of VOD, probably interfering with hemostasis or inducing chole- stasis and transaminitis, we were also interested in the incidence of transplant-related toxicity and mortality and, particularly, in the observed rate of VOD in these patients. The length of hormonal treatment, either at low or high dose, is also an important issue, which is not addressed by the authors. While we do recommend hormonal therapy after either autologous or allogeneic transplantation for long-term sequelae of ovarian failure, 6 we do not routinely give OC before or during transplantation and we recom- mend instead gonadotropin-releasing hormone (GnRH) agonists such as leuprorelin as prophylaxis or treatment of menorrhagia. 7,8 A first dose of GnRH analogue (leuprore- lin depot 3.75 mg) at least 30 days before the conditioning regimen followed by a second injection 28 days later is sufficient to prevent uterine bleeding 8 or to reduce menorrhagia in acute leukemia patients. 9 Of course, as also stated by the authors, prospective randomized trials are needed as well as surveys of local policies from transplant centers worldwide in order to ensure awareness of this specific issue and to promote guidelines for prophylaxis and treatment of menorrhagia after stem cell transplantation. S Sica 1 F Sora` 1 L Laurenti 1 P Chiusolo 1 N Piccirillo 1 P Scirpa 1 G Leone 2 1 Istituto di Ematologia, Universita ` Cattolica Sacro Cuore, Roma, Italia; and 2 Istituto di Ginecologia ed Ostetricia, Universita ` Cattolica Sacro Cuore, Roma, Italia References 1 Amsterdam A, Jakubowski A, Castro-Malaspina H et al. Treatment of menorrhagia in women undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 2004; 34: 363–366. 2 Hagglund H, Remberger M, Klaesson S et al. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation. Blood 1998; 92: 4568–4572. 3 Ganem G, Saint-Marc Girardin MF, Kuentz M et al. Veno- occlusive disease of the liver after allogeneic bone marrow transplantation in man. Int J Radiat Oncol Biol Phys 1988; 14: 879–884. 4 Nevill TJ, Barnett MJ, Klingemann HG et al. Regimen-related toxicity of a busulfan-cyclophosphamide conditioning regimen in 70 patients undergoing allogeneic bone marrow transplant- ation. J Clin Oncol 1991; 9: 1224–1232. 5 Klingemann HG, Shepherd JD, Reece DE et al. Regimen- related acute toxicities: pathophysiology, risk factors, clinical evaluation and preventive strategies. Bone Marrow Transplant 1994; 14 (Suppl 4): S-14. 6 Piccioni P, Scirpa P, D’Emilio I et al. Hormonal replacement therapy after stem cell transplantation. Maturitas 2004; 49: 327–333. 7 Chiusolo P, Salutari P, Sica S et al. Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation. Bone Marrow Transplant 1998; 21: 821–823. 8 Sica S, Salutari P, Chiusolo P et al. Hormonal therapy after stem cell transplantation and risk of veno-occlusive disease. Blood 1999; 93: 3154. 9 Sica S, Salutari P, Di Mario A et al. Treatment and prophylaxis of hypermenorrhea with leuprorelin in premenopausal women affected by acute leukemia at diagnosis. Am J Hematol 1996; 51: 248–249. Bone Marrow Transplantation (2005) 35, 827 & 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00 www.nature.com/bmt