Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy

Misso, Marie; Jang, Choon‐Gon; Adams, Jennifer R.; Tran, Jane; Murata, Yoko; Bell, Robin Jean; Boon, Wah Chin; Simpson, Evan R.; Davis, Susan Ruth

doi:10.1097/00042192-200512020-00016

Cited by 71 publications

(45 citation statements)

References 13 publications

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“…The estradiol levels detected in the blood of aged WT females likely reflect elevated peripheral production of this steroid from the increased adipose deposition noted in WT, but not KO, females. Indeed, a shift from ovarian to peripheral estrogen production has been documented in postmenopausal women, accompanied by increased expression and activity of aromatase in fat tissue (13,24,25). Thus, our data add support to the emerging concept that postmenopausal increases in circulating FSH, independent of changes in the levels or site of estrogen production, are responsible for age-related bone loss in females (26).…”

Section: Discussionsupporting

confidence: 80%

Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice

Perez

Jurisicova

Wise

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The menopausal transition in human females, which is driven by a loss of cyclic ovarian function, occurs around age 50 and is thought to underlie the emergence of an array of health problems in aging women. Although mice do not undergo a true menopause, female mice exhibit ovarian failure long before death because of chronological age and subsequently develop many of the same age-associated health complications observed in postmenopausal women. Here we show in mice that inactivation of the proapoptotic Bax gene, which sustains ovarian lifespan into advanced age, extends fertile potential and minimizes many age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Further, ovariectomy studies show that the health benefits gained by aged females from Bax deficiency reflect a complex interplay between ovary-dependent and -independent pathways. Importantly, and contrary to popular belief, prolongation of ovarian function into advanced age by Bax deficiency did not lead to an increase in tumor incidence. Thus, the development of methods for postponing ovarian failure at menopause may represent an attractive option for improving the quality of life in aging females.aging ͉ apoptosis ͉ menopause ͉ ovary A lthough the process of aging has been attributed in part to increased apoptosis in various tissues (1), animal models lacking cell death-regulatory genes are rarely subjected to longitudinal aging studies. In females, one of the first organ systems to fail with age is the reproductive axis, which in humans is a principal contributing factor to the onset of menopause (2). Ovarian failure, whether natural (age-related) or induced as a consequence of pathological insults, is driven by depletion of ovarian follicles, the hormonally active support structures that house oocytes, through apoptosis (3). As a consequence, dramatic changes in the endocrine activity of the female gonads ensue, which are thought to underlie the emergence of a spectrum of physiological and psychological health complications in aging females (2). Although it has been shown that aged female mice transplanted with ovaries of young donors live longer than nontransplanted control or ovariectomized females (4), it remains unclear whether postmenopausal health complications arise as a direct result of ovarian failure or simply reflect the aging process.Despite the fact that mice do not undergo a true menopause, female mice exhaust their follicle pool long before death because of chronological age (5), similar to that seen in humans (6). Further, aging female mice exhibit many of the same health complications associated with postmenopausal life in women (see below). In a previous study, we reported that oocyte and follicle loss in female mice lacking the proapoptotic Bax protein is attenuated, leading to a dramatic prolongation of ovarian function into very advanced age (7). To better understand the consequences of Bax deficiency and sustained ovar...

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Section: Discussionsupporting

confidence: 80%

Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice

Perez

Jurisicova

Wise

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…• Low serum testosterone levels are rarely the cause of HSDD; nonetheless, it remains possible that treatment with testosterone in women with low desire may prove beneficial for responsive sexual drive and may possibly alter orgasmic attainment if endogenous androgen levels are significantly reduced by cancer treatments. • Aromatization of androgens by adipose tissue is a concern in women with a history of breast cancer, because androgen administration may affect the plasma and cellular concentrations of estrogens 51 .…”

Section: S26mentioning

confidence: 99%

Management of Sexual Dysfunction in Postmenopausal Breast Cancer Patients Taking Adjuvant Aromatase Inhibitor Therapy

2007

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Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifeninduced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements-all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement-most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)-may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be attended with potential risk. Therefore, non-hormonal alternatives should in all cases be initially tried with the expectation that symptomatic relief can often be achieved.First-line therapy for urogenital symptoms, notably vaginal dryness and dyspareunia, should be the non-hormonal group of preparations such as moisturizers and precoital vaginal lubricants. In patients with estrogen-dependent breast cancer (notably those receiving anti-estrogenic adjuvant therapies) and severely symptomatic vaginal atrophy that fails to respond to non-hormonal options, menopausal hormone replacement or prescription vaginal estrogen therapy may considered. Systemic estrogen may be associated with risk and thus is best avoided. Judicious use of hormones may be appropriate in the wellinformed patient who gives informed consent, but given the potential risk, these agents should be prescribed only after mutual agreement of the patient and her oncologist. KEY WORDSAromatase inhibitor therapy, breast cancer, gynecologic side effects, hormone therapy, sexual dysfunction, si...

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“…Following reproductive senescence (menopause), the gonads fail to synthesize and secrete steroidal sex hormones. Compensatory increases in nongonadal synthesis of steroidal sex hormones have been recorded (85), nevertheless estrogen, progesterone, and testosterone deficiencies occur following reproductive senescence (26). Gonadotropin production and secretion also increase markedly following reproductive senescence, in a compensatory measure to stimulate sex hormone production; however, this is inevitably unsuccessful (26,78,88,122).…”

Section: Hormone Regulation and Reproductive Senescencementioning

confidence: 99%

Reproductive Hormones Modulate Oxidative Stress in Alzheimer's Disease

Barron

Fuller

Verdile

et al. 2006

Antioxidants & Redox Signaling

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Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy

Cited by 71 publications

References 13 publications

Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice

Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice

Management of Sexual Dysfunction in Postmenopausal Breast Cancer Patients Taking Adjuvant Aromatase Inhibitor Therapy

Reproductive Hormones Modulate Oxidative Stress in Alzheimer's Disease

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