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Chemotherapy for lung cancer may trigger early menopause

Pearl Toh
03 Jan 2019

Chemotherapy was associated with an increased risk of amenorrhoea among women with lung cancer, which may place them at a higher risk for early menopause, a study suggests.

“Understanding the risk for premature menopause after lung cancer-directed therapy is important to inform pretherapy counselling,” said the researchers. “Premenopausal lung cancer patients should be educated about the risk for chemotherapy-related amenorrhoea and the aforementioned lung cancer-specific amenorrhoea considerations before therapy initiation.”

The researchers analysed annual self-reported data on menstrual status of 182 premenopausal women (mean age at diagnosis 42.7 years) with lung cancer who participated in the Mayo Clinic Epidemiology and Genetics of Lung Cancer Research Program. Eighty-five patients were treated with chemotherapy within a year of diagnosis, during which 26 women from this patient subgroup also received targeted therapy. [Menopause 2018;doi:10.1097/GME.0000000000001199]

Among the patients treated with chemotherapy, 46 percent reported reaching menopause within a year after diagnosis compared with 15 percent of patients who reported so in the group of patients who did not receive chemotherapy and/or targeted therapy. All patients in the chemotherapy group had platinum-based therapy, and 64 percent also received taxanes.

There were also fewer chemotherapy-treated patients who remained premenopausal at the time of final survey (median duration after diagnosis, 3 years) compared with the those not treated with chemotherapy and/or targeted therapy (45 pe3rcent vs 69 percent).  

“Our results suggest that self-reported menopause occurs soon after a lung cancer diagnosis for more than half of all premenopausal women with lung cancer,” observed the researchers.

“Chemotherapy may cause acute amenorrhoea by killing growing follicles … [and] alkylating agents are especially notorious for their gonadotoxic effects,” they explained. “While prior studies suggest that alkylating agents are responsible for much of the ovarian toxicity experienced by young women with certain cancers, it is clear from these findings and others that nonalkylating agents can also damage ovarian function.”

Among the chemotherapy-treated patients, more than a quarter also received an antimetabolite (such as pemetrexed or gemcitabine; 32 percent) and topoisomerase inhibitor (etoposide, topotecan; 29 percent). Three patients out of the total population also received targeted therapy within a year of diagnosis, two of whom had yet to reach menopause at the final qualifying survey.

“Unique to the premenopausal survivor population is the concern that chemotherapy may diminish or eradicate the ovarian reserve,” the researchers highlighted. “If future fertility is desired, reproductive endocrinology should be consulted to discuss options for embryo and oocyte cryopreservation—the gold standard techniques for fertility preservation in this setting.”

Although the findings were limited by the small number of small sample size and a heterogeneous population, the researchers noted that the rate of amenorrhoea was “only slightly lower” than that observed in breast cancer survivors of similar age who received cyclophosphamide-containing regimens.

“Unlike in breast cancer, premature menopause is unlikely to improve prognosis in lung cancer, but preservation of fertility and subsequent pregnancies may be complicated by other sequelae of lung cancer treatment, such as chronic dyspnoea,” they pointed out.

 

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