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Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: the FEMIMS study

¹ Department of Cardiovascular and Neurological Science, Multiple Sclerosis Centre, University of Cagliari, Cagliari, Italy
² Department of Public Health, University of Cagliari, Cagliari, Italy
³ Multiple Sclerosis Centre of the Veneto Region, First Neurology Clinic, University Hospital of Padova, Padova, Italy
⁴ Department of Neurology, Multiple Sclerosis Centre, Ospedali Civili di Brescia, Brescia, Italy
⁵ Department of Neurology, University of Florence, Florence, Italy
⁶ Department of Neurological Sciences, University of Bari, Bari, Italy
⁷ Department of Neurosciences, Ophthalmology and Genetics, University of Genova, Genova, Italy
⁸ FEMIMS research group: M Galeotti (Unità Operativa di Neurologia, Ospedale di Lugo, Ravenna, Italy); C Cordioli (Multiple Sclerosis Centre, Department of Neurology, Ospedali Civili di Brescia, Italy); S Massole, L Musu, Coghe G (Multiple sclerosis Center, Department of Cardiovascular and neurological sciente, University of Cagliari, Italy); F Patti (Department of Neurosciences, MS Centre University of Catania, Italy); A Lugaresi (Department of Oncology and Neuroscience, Univ. "G. d'Annunzio" Chieti-Pescara, Italy); MR Tola (Department of Neurology, Ferrara); V Zipoli (Department of Neurology, University of Florence, Italy); GL Mancardi, E Capello (Departments of Neurosciences, Ophthalmology, and Genetics, Uiversity of Genova, Italy); C Solaro (Dip Neurologia ASL3 genovese Genova, Italy); D Caputo, Cavarretta R (MS Centre Fondazione Don Gnocchi, Milano, Italy); E Merelli (Department of Neurosciences, Modena, Italy); P Perini (Multiple Sclerosis Centre of the Veneto Region, First Neurology Clinic, University Hospital of Padova, Italy); A Francia (Third Clinic of Neurology, Department of Neurological Sciences, La Sapienza University, Rome, Italy); AP Batocchi nstitute of Neurology, Department of Neurosciences, Catholic University, Rome, Italy); R Bergamaschi, E Tavazzi (Multiple Sclerosis Center, Neurological Institute C. Mondino University of Pavia, Italy); P Cavalla, S Masera (Department of Neurosciences, University of Turin, Italy); A Bertolotto, M Capobianco (MS Centre Department of Neurology, San Luigi Gonzaga Hospital Torino, Italy); M Zorzon (Department of Clinical Medicine and Neurology, University of Trieste, Italy); A Ghezzi, M Zaffaroni, (Centro Studi Sclerosi Multipla, S. Antonio Abate Hospital, Gallarate, Italy).

^* To whom correspondence should be addressed.

	Abstract

Background

Improved prognosis in women with multiple sclerosis (MS) undergoing immunosuppressive treatment with mitoxantrone (MITO) has led to an increased interest in the effect of such treatments on fertility. FErtility and Mitoxantrone In MS (FEMIMS) is a collaborative retrospective study aimed at evaluating the impact of MITO treatment on fertility in women with MS.

Methods

Occurrence of chemotherapy-induced amenorrhea (CIA) was evaluated in 189 women with MS treated with MITO before the age of 45. An "ad hoc" questionnaire, paying particular attention to onset of CIA either during or post-MITO treatment, was administered to each patient. The probability of CIA was calculated using a multivariate logistic regression analysis taking into account age at exposure, cumulative dose, and use of estroprogestinic (EP) drugs during treatment.

Results

Forty-eight (26%) patients presented CIA following MITO. The probability of CIA was increased by 2%/mg/m² of cumulative dose and by 18% for each year of age, whereas it was reduced by administration of EP during treatment.

Conclusions

MITO treatment may affect reproductive capacity in women with MS. Patients of childbearing age should be properly counseled before MITO treatment and EP therapy should be administered to reduce the risk of CIA.

Key Words: amenorrhea, estroprogestinic drug, fertility, immunosuppressive drugs, mitoxantrone, multiple sclerosis

First published on August 13, 2008, doi:10.1177/1352458508094882

Multiple Sclerosis 2008;14:1225.

A more recent version of this article appeared on November 1, 2008


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