Menopausal Hormone Replacement Therapy and Risk of Ovarian Cancer

Lacey, J.

doi:10.1001/jama.288.3.334

Cited by 541 publications

(219 citation statements)

References 48 publications

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“…These findings are consistent with other prospective studies that have reported increased risks of between 25 and 107% for estrogen-only use and ovarian cancer risk [10][11][12][13][14][15][16]. The evidence for an association with use of estrogen plus progestin therapy is less consistent; most case-control studies have found no association [17- 23], while some [11,14,16], but not all prospective studies have reported small increased risks [10,12,13,15]. The Women's Health Initiative trial found a non-significant 58% higher risk (95% CI, 0.77-3.24) for estrogen plus progestin HT, based on 32 cases of ovarian cancer during an average of 5.6 years of follow-up [24].…”

Section: Discussionsupporting

confidence: 92%

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

Tsilidis

Allen

Key

et al. 2011

Cancer Causes Control

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The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations.

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Section: Discussionsupporting

confidence: 92%

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

Tsilidis

Allen

Key

et al. 2011

Cancer Causes Control

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“…However, high levels of estrogen are associated with epileptic seizures (5,7,8), and exacerbate symptoms of Parkinson's disease (7). In addition, recent studies have shown negative secondary effects of estrogen replacement therapy during post-menopausal treatment (9)(10)(11)12). Corticosteroids, while necessary for coping with stress, may have deleterious effects if present in excess (13,14).…”

Section: Supporting Textmentioning

confidence: 99%

Steroid Control of Longevity in Drosophila melanogaster

Simon

Shih

Mack

et al. 2003

Science

257

186

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Ecdysone, the major steroid hormone of Drosophila melanogaster , is known for its role in development and reproduction. Flies that are heterozygous for mutations of the ecdysone receptor exhibit increases in life-span and resistance to various stresses, with no apparent deficit in fertility or activity. A mutant involved in the biosynthesis of ecdysone displays similar effects, which are suppressed by feeding ecdysone to the flies. These observations demonstrate the importance of the ecdysone hormonal pathway, a new player in regulating longevity.

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“…Postmenopausal oestrogen-only hormone replacement therapy has been associated with increased occurrence of endometrial, ovarian and breast cancers (Lacey et al 2002, Beral et al 2005b; however, inclusion of progestagens in the hormone replacement therapy (HRT) formulations is reported to reduce risk (Beral et al 2005a), consistent with the physiological effect of progesterone in counteracting oestrogen-driven proliferation. Furthermore, the use of the combined oral contraceptive pill is apparently protective against endometrial cancer risk (Emons et al 2000), an effect that persists even after discontinuation of use (La Vecchia et al 1996).…”

Section: Figurementioning

confidence: 98%

Endocrine disruption of oestrogen action and female reproductive tract cancers

Gibson

Saunders

2013

Endocrine-Related Cancer

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Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homoeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids, and oestrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women, with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high BMI and exposure to oestrogens or synthetic compounds such as tamoxifen. Studies on cell and animal models have provided evidence that many EDC can bind oestrogen receptors and highlighted early life exposure as a window of risk for adverse lifelong effects on the reproductive system. The most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol. Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence collected to date.

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Menopausal Hormone Replacement Therapy and Risk of Ovarian Cancer

Cited by 541 publications

References 48 publications

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

Steroid Control of Longevity in Drosophila melanogaster

Endocrine disruption of oestrogen action and female reproductive tract cancers

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