The Menopause: Health Implications and Clinical Management

Greendale, Gail A.; Judd, Howard L.

doi:10.1111/j.1532-5415.1993.tb06953.x

Cited by 103 publications

(35 citation statements)

References 129 publications

(162 reference statements)

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“…Ospemifene is a new SERM currently being developed for the treatment of post-menopausal VVA, a condition that adversely affects the quality of life for approximately 40% of post-menopausal women [21,22]. Currently, available therapies for VVA include hormone replacement therapy, transvaginal oestrogen products, and non-hormonal lubricants and moisturizers [23]; however, there are limitations associated with each of these treatments [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic Effects of Ospemifene in Rhesus Macaques: A Pilot Study

Wurz¹,

Hellmann-Blumberg

DeGregorio³

2008

Basic Clin Pharma Tox

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Ospemifene (Ophena™) is a new selective oestrogen receptor modulator currently in phase III clinical development for treatment of post-menopausal vulvar and vaginal atrophy. In the present study, we examined the pharmacokinetics, toxicity, and DNA adduct forming potential of ospemifene in the liver and endometrium of rhesus macaques following single and subchronic dosing schedules to better understand the potential toxicologic effects of ospemifene. During single weekly dosing, six macaques were administered 35 mg/kg/week ospemifene orally for 3 weeks. Pharmacokinetics, haematologic toxicity, uterotrophic effects and serum cholesterol levels were monitored. Additionally, two animals were subchronically dosed with 60 mg ospemifene for 9 weeks, followed by 12 mg/day for 3 weeks. Serum cholesterol and pharmacokinetics were monitored, and serial liver and endometrial biopsies were collected during and after treatment to evaluate DNA adduct formation. Following single weekly dosing, no significant haematologic toxicities or uterotrophic effects associated with ospemifene were observed. Peak absorption was 4-5 hr, and the elimination half-life was approximately 22 hr. Serum low-density lipoprotein and triglyceride levels trended lower while no other effects on serum lipids were observed. Subchronic dosing resulted in no haematologic toxicity, a lowering of low-density lipoprotein and triglyceride levels, and an increase in high-density lipoprotein levels that were reversed following cessation of dosing. No clinically relevant uterine or endometrial effects were observed, and no DNA adducts were detected in the liver or endometrial biopsies. The results of our pilot study show that ospemifene may lack genotoxic and toxic effects while having a favourable pharmacokinetic profile.Ospemifene (Ophena™) is a new selective oestrogen receptor modulator (SERM) that is currently in late phase III clinical development for the treatment of vulvar and vaginal atrophy (VVA) in post-menopausal women. Results from phases I and II clinical studies have shown that ospemifene is generally safe and well tolerated, has pharmacokinetics suitable for once daily dosing, that it has positive effects on markers of bone turnover similar to raloxifene, and that it does not adversely affect climacteric symptoms, vascular markers or quality of life [1][2][3][4][5]. No safety concerns have been raised in any of the clinical trials completed to date.Similar to other SERMs like tamoxifen and raloxifene, ospemifene has tissue-specific oestrogenic or anti-oestrogenic effects: it acts as an anti-oestrogen in the breast [6][7][8][9], has neutral to weak oestrogen agonist effects in the endometrium [5,10,11], and is predominantly oestrogenic in the bone [2,3,6]. As a triphenylethylene derivative, ospemifene shares some similarities with tamoxifen, but there are also some important differences. Unlike tamoxifen, which acts as an oestrogen agonist in the endometrium [12], ospemifene has been shown to have neutral to weak oestrogen agonist effects ...

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Section: Discussionmentioning

confidence: 99%

Pharmacologic Effects of Ospemifene in Rhesus Macaques: A Pilot Study

Wurz¹,

Hellmann-Blumberg

DeGregorio³

2008

Basic Clin Pharma Tox

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“…The cessation of ovarian estrogen secretion is illustrated by the marked decline in circulating E 2 levels. This easily measurable change in circulating E 2 levels coupled with the demonstrated beneficial effects of exogeneous estrogens on menopausal symptoms (Grady et al 1992, Greendale & Judd 1993, Lomax & Schonbaum 1993, Archer et al 1999) and bone resorption (Weiss et al 1980, Christiansen et al 1982, Genant et al 1990, Harris et al 1991, Grady et al 1992, Field et al 1993, Lindsay 1993, Archer et al 1999, Women's Health Initiative 2002 has focused most of the efforts of HRT on various forms of estrogens as well as on combinations of estrogen and progestin in order to avoid the risk of endometrial cancer induced by estrogens administered alone.…”

Section: Role Of Dhea In Womenmentioning

confidence: 99%

Is dehydroepiandrosterone a hormone?

Labrie¹,

Luu‐The²,

Bélanger³

et al. 2005

Journal of Endocrinology

384

242

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Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cellspecific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogensensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.

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“…[1][2][3] The altered morbidity profile of postmenopausal women not only decreases their quality of life but also results in a substantial increase in the demand for medical services. [2][3][4] Menopause is defined as the permanent cessation of menstruation caused by the loss of follicular activity in the ovaries. 1 Natural menopause is recognized after 12 consecutive months of amenorrhea with no other pathological or psychological causes.…”

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confidence: 99%

Reproductive and lifestyle factors associated with early menopause in Mexican women

et al. 2006

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ResumenObjetivo. Evaluar la relación entre factores reproductivos, estilo de vida y la ocurrencia de menopausia natural temprana. Material y métodos. Un estudio de casos y controles fue conducido en una población basal de 2 510 mujeres participantes en la "Cohorte de trabajadores IMSS". Los casos fueron definidos como aquellas mujeres que presentaron la menopausia natural a los 47 años o menos. La información fue colectada a través de cuestionarios autoapicables. AbstractObjective. The purpose of this study was to evaluate the relationship between certain reproductive and lifestyle factors and the occurrence of early natural menopause. Material and Methods. A case/control study was conducted on a basal population of 2 510 women participating in the "Mexican Institute of Social Security health workers cohort study". Cases were defined as those women for whom natural menopause presented by age 47. Information was obtained through a self-administered questionnaire. Results.

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The Menopause: Health Implications and Clinical Management

Cited by 103 publications

References 129 publications

Pharmacologic Effects of Ospemifene in Rhesus Macaques: A Pilot Study

Pharmacologic Effects of Ospemifene in Rhesus Macaques: A Pilot Study

Is dehydroepiandrosterone a hormone?

Reproductive and lifestyle factors associated with early menopause in Mexican women

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