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Whether periods return after chemotherapy depends mostly on age and on which drugs were given. In the one study that recorded bleeding daily, about two thirds of women who stopped bleeding for six months after an anthracycline regimen started again, usually within a year. Of those who went two years without a period, one in ten bled again and none regained regular cycles.
Alkylating drugs destroy primordial follicles, and because the ovarian reserve is fixed at birth, the loss is permanent. What varies is how much reserve was there to begin with, which is why age is the strongest predictor.
The best prospective data come from a cohort of 595 American women aged 20 to 45 who kept daily bleeding records for a median of 45 months. In the month after standard doxorubicin and cyclophosphamide, with or without a taxane, about 16 per cent had monthly bleeding, against 48 per cent after cyclophosphamide, methotrexate and fluorouracil. After the anthracycline regimens there was "a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period". The companion analysis of 466 women in the same cohort found that about 41 per cent had at least six months of amenorrhoea and a further 29 per cent at least a year; roughly half of those with six months of amenorrhoea and 29 per cent of those with a year resumed bleeding within the next three years, "usually in the year after their amenorrheic episode". Of the 23 per cent who had two years without a period, 10 per cent bled again "but none had regular menses". Both cohorts were recruited between 1998 and 2002, so they describe older regimens; OnCo could not find an equivalent prospective dataset for today's schedules.
Temporary ovarian suppression during chemotherapy is the one intervention that changes this. In the POEMS trial, 257 premenopausal women with hormone-receptor-negative breast cancer were randomised to chemotherapy with or without goserelin; among the 135 with complete primary endpoint data the ovarian failure rate at two years was 8 per cent with goserelin and 22 per cent without, and pregnancies occurred in 21 against 11 per cent of the 218 evaluable women. The trial's own authors note that "missing data weaken interpretation of the findings". Pooling 873 patients across five trials, premature ovarian insufficiency occurred in 14.1 per cent with the agonist and 30.9 per cent without, with more pregnancies and no difference in disease-free or overall survival.
ASCO's position is deliberately careful: "There is conflicting evidence to recommend gonadotrophin-releasing hormone agonists (GnRHa) and other means of ovarian suppression for fertility preservation", and "GnRHa should not be used in place of proven fertility preservation methods." Egg, embryo and ovarian tissue freezing remain the methods that preserve fertility, and they belong before treatment starts.
What comes back, and when: partial, age-dependent, and mostly settled within the first year or two. Return of periods is not the same as return of fertility, and ovarian reserve after recovery is lower than it was, which matters for anyone planning a pregnancy years later. Two years of amenorrhoea after chemotherapy is, on this evidence, close to the end of the story.
Cyclophosphamide and other alkylating agents damage primordial follicles directly and the growing follicle pool indirectly, accelerating depletion of a reserve that cannot be replenished. A gonadotrophin-releasing hormone agonist suppresses the pituitary axis and may reduce ovarian perfusion and recruitment during the exposure, which is the proposed, unproven mechanism of protection.
Query for this technology: (TITLE:"Ovarian function after chemotherapy: who recovers, and when" OR ABSTRACT:"Ovarian function after chemotherapy: who recovers, and when") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Ovarian function after chemotherapy: who recovers, and when, not a curated reading list.
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