Triptorelin May Thwart Chemotherapy-Induced Early Menopause

Temporary ovarian suppression using triptorelin may decrease the rate of early menopause in premenopausal women with early-stage breast cancer undergoing adjuvant or neoadjuvant chemotherapy, according to data from a multicenter phase III trial. Results showed that administration of the gonadotropin-releasing hormone (GnRH) agonist before and during chemotherapy was associated with a nearly 20% absolute reduction in the occurrence of early menopause.

“This treatment can therefore be offered to premenopausal patients with breast cancer who wish to decrease the risk of permanent ovarian failure associated with chemotherapy,” said Lucia Del Mastro, MD, with the Istituto Nazionale per la Ricerca sul Cancro in Genova, Italy, and colleagues.

In the Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients—Gruppo Italiano Mammella 6 (PROMISE-GIM6) study, 281 women were randomized before starting chemotherapy to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before initiation of chemotherapy and then every 4 weeks throughout chemotherapy.

Study participants were premenopausal women aged 18 to 45 years who had histologically proven stage I, II, or III breast cancer and were eligible for adjuvant or neoadjuvant chemotherapy.

Roughly 6% of women with breast cancer are diagnosed before they reach their 40s, and almost 1 in 200 women will develop the disease before she reaches her 40s, Del Mastro and associates wrote. Most young patients with breast cancer receive chemotherapy, hormonal therapy, or both. Chemotherapy regimens are associated with an incidence of long-term amenorrhea of at least 40%.

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This treatment can therefore be offered to premenopausal patients with breast cancer who wish to decrease the risk of permanent ovarian failure associated with chemotherapy. ”

—Lucia Del Mastro, MD

The authors said that premature menopause has major sequelae, including vasomotor symptoms, sexual dysfunction, and infertility. Infertility, in particular, is a primary concern for young women with breast cancer and may affect their treatment decisions in almost one-third of cases. While there is no available treatment for preventing chemotherapy-induced ovarian failure, temporary ovarian suppression with a GnRH agonist during chemotherapy has been shown in animal studies to decrease ovarian toxicity, they added.

The primary outcome measure in their study was the incidence of chemotherapyinduced early menopause. Early menopause was defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone for 1 year after the completion of chemotherapy.

The analysis found that early menopause occurred in 25.9% of women receiving chemotherapy alone and 8.9% of women treated with chemotherapy plus triptorelin, for an absolute difference of —17% (95% confidence interval [CI], –26% to –7.9%; P <.001).

Only treatment with triptorelin was associated with a decrease in early menopause, with an odds ratio of 0.28 (95% CI, 0.14-0.59).

Women who received tamoxifen were less likely to recover menses. Also, triptorelin conferred more benefit in patients with hormone receptor-negative disease than in women with hormone receptorpositive disease. Patient age and the type of chemotherapy did not significantly affect the risk of early menopause.

Del Mastro and associates pointed out that GnRH agonistinduced ovarian suppression is superior to embryo cryopreservation via in vitro fertilization and oocyte or ovarian tissue cryopreservation for maintaining fertility. Notably, ovarian suppression with GnRH agonists does not require a male partner, is easy to administer, and is less invasive. Also, chemotherapy does not need to be postponed.

Del Mastro L, Boni L, Michelotti A, et al. Effect of the gonadotropinreleasing hormone analogue triptorelin on the occurrence of chemotherapyinduced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA. 2011;306(3):269-276.