The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease

Abstract

In this cohort of young women with rheumatologic disease, more women with prior CYC than without had amenorrhea, nulliparity, and infertility. GnRH-a co-therapy may prevent these adverse effects of CYC.

Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study

“…Studies have reported ovarian insufficiency in 10-83 % of female SLE patients treated with CYC, depending primarily on the subject's age at initiation of treatment and cumulative CYC dose [25][26][27]. Medeiros et al showed that SLE patients treated with a cumulative CYC dose of greater than 10 g had a 3.2 times higher risk of developing ovarian insufficiency than patients receiving a cumulative dose lower than 10 g [28].…”

Ovarian Function and Reproductive Outcomes of the Female Patients with Systemic Lupus Erythematosus and the Strategies to Preserve their Fertility

“…In their series, even though women with prior cyclophosphamide exposure were 4 years younger at diganosis than those without cyclophosphamide, 30.4% of them had cessation of menses compared to 0% of those without cyclophosphamide (p<0.05). Of the women with prior cyclophosphamide exposure those with loss of menses were older at study enrollment, older at cyclophosphamide treatment and higher cumulative doses of cyclophosphamide than those who retained menstrual function [18]. AMH appear to be a reliable indicator of residual ovarian reserve postexposure to cyclophosphamide based on the accumulating evidence of the aforementioned studies.…”

“…• Chronic inflammatory state may prevent the proper functioning of the hypothalamic-pituitary-ovarian axis (HPO) [15] • Autoimmune ovarian injury most commonly in the form of autoimmune oophoritis may hamper ovarian function [16] • Lupus flares are associated with hyperprolactinemia, which may interfere with ovulation process and affect immune activity [17] • Thrombocytopenia, antiphospholipid antibodies, and the use of glucocorticoids and/or nonsteroidal anti-inflammatory drugs can contribute to menorrhagia [14] • Temporary or even permanent early (or premature) amenorrhea may result from autoimmune ovarian injury or from the administration of cytotoxic agents such as cyclophosphamide [18] Figure 1: Contributory factors causing menstrual irregularity, ovarian failure and infertility in women with systemic lupus erythematosus. SLE involves many organ systems.…”

“…Currently serum AMH levels and the number of antral follicles counted on the ultrasound at early follicular phase of the menstrual cycle are the most reliable indicators of ovarian reserve. In the recent years a number of studies documented that cyclophosphamide administration is the most significant risk factor for ovarian failure, and that AMH is a sensitive and reliable marker of ovarian reserve and damage post exposure to cyclophosphamide in female patients with SLE [18][19][20][32][33][34]. For instance, Harward et al reported a case series study of women diagnosed with SLE, vasculitis and scleroderma prior to age 35 (23 had prior cyclophosphamide exposure, 20 did not).…”

Irreversible organ damages in patients with systemic lupus erythematosus. SLICC damage index

“…Золотым стандартом поликом-понентной терапии активной СКВ является комбинация вы-С О В P E М Е Н Н А Я Р Е В М А Т О Л О Г И Я № 1 ' 1 6 О Б З О Р Ы соких доз ГК и ЦФ. Однако и ЦФ вносит существенную леп-ту в развитие органных поражений, вызывая аменорею, бес-плодие и повышая риск развития опухолей [55]. Есть надеж-да, что появление генно-инженерных биологических препа-ратов (белимумаб, ритуксимаб, эпратузумаб), применение которых не ассоциируется с развитием «традиционных» ор-ганных повреждений, сделает терапию СКВ не только более эффективной, но и более безопасной [56].…”