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The influence of reproductive factors on bone mass at six skeletal sites was assessed in an age-stratified random sample of white women residing in Rochester, Minnesota. After age-adjustment, whether or not women had ever breastfed, total duration of breastfeeding and duration of breastfeeding per child were not associated with reduced bone mineral, but breastfeeding for more than 8 months was associated with greater bone mineral at some sites. There were no consistent effects on bone mineral, after adjusting for age, of gravidity or parity, age at menarche, age at first delivery, use of oral contraceptives or estrogen replacement therapy, various sex hormones, nor any of the other reproductive factors assessed. There was a strong protective effect of obesity, which was also correlated with a number of the reproductive variables. While animal studies suggest that pregnancy and lactation may be associated with calcium loss from the skeleton, these data indicate that such factors have little long-term impact on bone mass in humans and little potential for identifying women at high risk of osteoporosis later in life.

Elderly women with the lowest serum estrogen levels are at the greatest risk of bone loss and fractures, but it is controversial whether the ovaries contribute to estrogen production after menopause, and therefore, whether bilateral oophorectomy in postmenopausal women might have adverse skeletal effects.

We have evaluated the relation between alkylating agents and leukemic disorders in 3363 1-year survivors of ovarian cancer who were treated in five randomized clinical trials and at two large medical centers. Overall, 28 patients developed acute nonlymphocytic leukemia (expected, 1.2) and 7 developed preleukemia. A 93-fold increased risk for acute nonlymphocytic leukemia was seen in 1794 women treated with chemotherapy; the incidence of leukemic disorders was 7.7/1000 women per year. Risk was highest 5 to 6 years after the first treatment and appeared to decrease thereafter. The use of radiation therapy did not affect risk. The 10-year cumulative risk (mean +/- SE) of acquiring a leukemic disorder was 8.5% +/- 1.6% after treatment with any alkylating agent, 11.2% +/- 2.6% after treatment with melphalan, and 5.4% +/- 3.2% after cyclophosphamide treatment. A dose-response relationship was apparent in 605 women receiving melphalan and suggested in 333 women receiving cyclophosphamide. Women receiving melphalan were two to three times as likely to develop leukemic disorders than were women receiving cyclophosphamide. These data indicate that choice of chemotherapeutic agent and drug dosage may influence significantly the risk for long-term adverse effects of cancer therapy.