Cigarette Smoking, Serum Estrogens, and Bone Loss during Hormone-Replacement Therapy Early after Menopause

Jensen, Jytte; Christiansen, Claus; Rødbro, P.

doi:10.1056/nejm198510173131602

Cited by 339 publications

(117 citation statements)

References 12 publications

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“…However, coitrary to what might be expected, parity and (early) age at menarche were not (positively) related to bone mass. Smoking may enhance both the metabolic inactivation of oestrogens (Jensen et al, 1985) and early menopause (Lesko et al, 1985), and therefore could have a negative influence on BMD. the present study is significantly reduced in osteoporotic women compared to controls (Riggs et al, 1981;Kr0lner & Nielsen, 1982).…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer

Bruning

Pit²,

Jong-Bakker³

et al. 1990

Br J Cancer

170

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Summary Lumbar bone mineral density (BMD) determination by dual photon absorptiometry was used to study the influence of adjuvant chemotherapy for premenopausal breast cancer on the risk of premature osteoporosis. Six cycles of combination chemotherapy caused ovarian failure in 31 of 44 (71 %) women, amenorrhoea mostly already beginning during treatment. In contrast, only seven of 44 (16%) women, who were pair-matched for age and year of breast cancer surgery and had not been treated with chemotherapy, were post-menopausal at the time of measurement. The mean interval after breast surgery was 3.5 years. The significantly decreased BMD in the treated group (1.17 compared to 1.29 g cm-2) could only be explained by the high incidence of menopause in these women, which on average occurred 10 years prematurely. Extrapolation of these findings suggests that adjuvant chemotherapy may precipitate osteoporotic fractures by some 10 years in a considerable proportion of women cured of premenopausal breast cancer.Gradual loss of bone matrix and mineral is a consequence of ageing leading to osteoporosis. In general, women start off with less peak adult bone mass than men and consequently develop more symptoms from osteoporosis. As a result a considerable proportion of women suffer from spontaneous fractures in later life (Gordan, 1978;Nordin, 1980; NIH Consensus Statement, 1984). Various data suggest that in osteoporosis there is a disproportionately greater loss of trabecular bone from the axial skeleton compared to cortical bone from appendicular sites (Riggs et al., 1981).The average annual loss of bone mass measured by bone mineral density (BMD) in women before menopause amounts to 1-2%, but may rise to some 6-8% during the first 2-5 years after menopause (Krolner & Pors Nielsen, 1982;Genant et al., 1982). This dramatic temporary increase in the rate of bone loss around natural menopause or after bilateral ovariectomy has been ascribed to a ceasing protection from bone loss by ovarian hormones (Riggs et al., 1981(Riggs et al., , 1982(Riggs et al., , 1986Genant et al., 1982;Johnston et al., 1985;Richelson et al., 1984). Oestrogen replacement therapy effectively prevents osteoporosis in post-menopausal women if started within a few years after menopause (Riis, 1987;Lindsay et al., 1976;Christiansen et al., 1980;Recker et al., 1977).Adjuvant chemotherapy in premenopausal women treated for breast cancer frequently leads to diminished ovarian function and premature menopause (Henderson, 1987). Since early menopause is one of the strongest predictors of osteoporosis (Richelson et al., 1984), we anticipated that the widely used adjuvant chemotherapy regimen of cyclophosphamide, methotrexate and 5-fluorouracil (CMF), might seriously precipitate osteoporosis.To investigate this possibility we have compared the bone mineral density of the lumbar spine between women who had been treated with adjuvant CMF and women, matched for age and time of premenopausal breast cancer surgery, who received no such treatment. Patients were consi...

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Section: Discussionmentioning

confidence: 99%

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer

Bruning

Pit²,

Jong-Bakker³

et al. 1990

Br J Cancer

170

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“…Hence, factors associated with reduced circulating oestrogen levels may consequently reduce the risk of this malignancy (Baron, 1984;Baron et al, 1990). In this regard, it has been hypothesised that smoking might be inversely related to levels of circulating oestrogen (Jensen et al, 1985;Baron et al, 1990;Weiderpass and Baron, 2001). Supporting this hypothesis are studies that have shown that smoking is associated with increased risk of osteoporosis (Jensen et al, 1985;Jensen and Christiansen, 1988) and may attenuate the reduction in serum total and low-density lipoprotein cholesterol associated with exogenous hormone use (HRT) (Jensen and Christiansen, 1988).…”

Section: Epidemiologymentioning

confidence: 99%

A prospective cohort study of cigarette smoking and the risk of endometrial cancer

2002

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Case -control studies have shown inverse associations between cigarette smoking and endometrial cancer risk. However, two small prospective cohort studies have not clearly supported an association. Moreover, quantitative measures of smoking have been examined infrequently. Our aim was to study the association between smoking and endometrial cancer risk in a large prospective cohort. We used proportional hazards models to estimate hazard ratios relating cigarette smoking to endometrial cancer risk among 70 591 women aged 40 -59 years at recruitment into a randomised controlled trial of mammography screening for breast cancer. During an average of 10.6 years of follow-up (751 833 person -years), a total of 403 women were diagnosed with incident endometrial cancer. We found that a reduced endometrial cancer risk was evident only among women who currently smoked 20 cigarettes per day or more (hazard ratio=0.62, 95% CI=0.42 -0.92, P for trend=0.03). There was some suggestion of an inverse association with smoking duration, but this was less clear. The association did not vary with menopausal status, relative body weight, or the use of hormone replacement therapy, but it appeared to be stronger among parous than nulliparous women. The underlying biological mechanisms of this association remain unclear.

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“…Jensen et al (1985) found that smoking reduced the serum concentrations of El and E2 in postmenopausal women taking ERT: they could not detect any effect of smoking on endogenous El or E2 concentrations, but these concentrations were at the lower limit of sensitivity of their assay. They concluded that smoking increases metabolic clearance of E2.…”

mentioning

confidence: 92%

The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk

Key¹,

Pike²

1988

Br J Cancer

484

333

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Summary The 'unopposed oestrogen hypothesis' for endometrial cancer maintains that risk is increased by exposure to endogenous or exogenous oestrogen that is not opposed simultaneously by a progestagen, and that this increased risk is due to the induced mitotic activity of the endometrial cells. Investigation of the mitotic rate during the menstrual cycle shows that increases in plasma oestrogen concentration above the relatively low levels of the early follicular phase do not produce any further increase in the mitotic rate of endometrial cells. A modification of the unopposed oestrogen hypothesis which includes this upper limit in the response of endometrial cells to oestrogen is consistent with the known dose-effect relationships between endometrial cancer risk and both oestrogen replacement therapy and postmenopausal obesity; it also suggests that the mechanism by which obesity increases risk in premenopausal women involves progesterone deficiency rather than oestrogen excess, and that the protective effect of cigarette smoking may be greater in postmenopausal than in premenopausal women.Detailed analysis of the age-incidence curve for endometrial cancer in the light of this hypothesis suggests that there will be lifelong effects of even short duration use of exogenous hormones. In particular, 5 years of combination-type oral contraceptive use is likely to reduce a woman's lifetime risk of endometrial cancer by some 60%; whereas 5 years of unopposed oestrogen replacement therapy is likely to increase her subsequent lifetime risk by at least 90%; and even 5 years of 'adequately' opposed therapy is likely to increase subsequent lifetime risk by at least 50%.Epidemiological studies have shown that the risk of developing endometrial cancer increases markedly with increasing weight and with use of oestrogen replacement therapy (ERT) or sequential-type oral contraceptives, and decreases markedly with use of combination-type oral contraceptives (COCs) (Weiss et al., 1980;Henderson et al., 1983). These risk factors can all be explained in terms of the 'unopposed oestrogen hypothesis' for endometrial cancer (Siiteri, 1978;Henderson et al., 1982).In essence the unopposed oestrogen hypothesis maintains that endometrial cancer risk is increased by exposure to endogenous or exogenous oestrogen which is not opposed by progesterone or a synthetic progestagen, and that this increased risk is caused by the increased mitotic activity of the endometrium induced by such exposure. It has, however, not been clear that this hypothesis can explain the high relative risk associated with obesity in premenopausal women.In this paper we first argue, on the basis of studies of premenopausal hormone levels and of endometrial mitotic rates, that endometrial cell division is not increased by increases in plasma oestrogen concentration above early follicular levels. We show that epidemiological studies of the effects of different doses of ERT on endometrial cancer risk are consistent with the existence of such an upper limit, as are studies...

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Cigarette Smoking, Serum Estrogens, and Bone Loss during Hormone-Replacement Therapy Early after Menopause

Cited by 339 publications

References 12 publications

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer

A prospective cohort study of cigarette smoking and the risk of endometrial cancer

The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk

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