Hormone-related diseases

First we shall describe the effects of tamoxifen, a first-generation SERM used as adjuvant treatment in women with breast cancer, on uterine leiomyomas and endometriosis. Considerable space will be devoted to raloxifene, a second-generation SERM administered for the prevention and treatment of postmenopausal women recently tested for the treatment of these two sex-hormone-related diseases. Unfortunately, at present no or very little data are available on the new third-generation SERMs such as lasofoxifene, idroxifene, droloxifene, ospemifene, azomifene, fulvestrant, and MDL 103.323. 

HORMONE-RELATED DISEASES MECHANISMS OF HORMONE ACTION... 

Because hormones are so influential in the regulation of meta-bolic processes, it is not surprising that there are numerous hormone-related diseases. In general, such diseases are caused by either overproduction or underproduction of a specific hormone or the insensitivity of target cells. 

As outlined in Chapter 2, ECD are chemicals that can cause hormonal related diseases and dysfunctions that can be effective even at very low levels (at parts per trillion, levels at which most chemicals have never been tested). ECD became a significant focus of environmental science and medicine in recent years because of its critical importance in heath. A wide range of chemicals, both natural compounds (phytoestrogens) and some synthetic chemicals (including polychlorinated biphenyls (PCB), dioxins, certain preservatives and metal ions, even certain woods) are all suspected of being capable of endocrine disruption in humans. 

As outlined previously, ECD are chemicals that can cause hormonally related diseases and dysfunction that can be effective at very low levels (even at parts per trillion levels... 

In 1996, Colborn et al. highlighted the potential health implications of these additives and their ability to disrupt the natural function of the endocrine system. The number of suspected endocrine disrupting chemicals (EDCs) has subsequently grown. However, the causality between exposure to EDCs and adverse human health effects is unclear and controversial due to the multifactorial etiologies of such a hormone-related disease. ... 

Prostate Cancer. Evidence that phytoestrogens can influence the incidence of male-speciflc diseases is restricted to prostate cancer, and is largely of an observational nature. In the UK, prostate cancer is the most common hormone-related cancer in men. However, like breast cancer in women, it is comparatively rare as a clinically evident disease in men living in Asian countries. 

In order to get recent advances on the effects of phytoestrogens on hormonal-dependent diseases as well as on human supplementation trials, it might be useful to refer to http //www.venus-ca.org/ (EU-funded project on dietary exposure to phytoestrogens and related compounds and effects on skeletal tissues) http //www.phytos.org (EU-funded project on the prevention of osteoporosis by nutritional phytoestrogens) http //www.phytoprevent.org (EU-funded project on the role of phytoestrogens in the prevention of breast and prostate cancer) and http //www.nutrition.tum.de/isoheart.htm (EU-funded project on cardiovascular health of postmenopausal women). 

The most common benign gynecological diseases, for prevalence and related economic costs, are probably uterine leiomyomas and endometriosis (Stewart 2001 Missmer et al. 2003). Notwithstanding the fact that both conditions are characterized by a sex-hormone-related development and by the possibility of a medical treatment consisting of hormonal manipulation, at present the main approach to these conditions is surgical excision (Palomba et al. 2006a Olive etal. 2001). 

The mechanism of G a disease may resnlt from insnfficient parathyroid hormone-related peptide signaling by the parathyroid hormone receptor 1 (PTHRl) in chondrocytes. This deficiency may inhibit the differentiation of chondrocytes within the endochondral growth plate (88,89). A variety of parathyroid hormone abnormalities can result. 

In recent years, concern that chemicals might inadvertently be disrupting the endocrine system of humans and wildlife has increased. The concerns regarding exposure to these endocrine disrupters are based on adverse effects observed in certain wildlife, fish, and ecosystems increased incidences of certain endocrine-related human diseases and adverse effects observed in laboratory animals exposed to certain chemicals. The main effects reported in both wildlife and humans concern reproductive and sexual development and function altered immune system, nervous system, and thyroid function and hormone-related cancers. Endocrine dismption is not considered a toxicological endpoint in its own right, but a functional change or toxicological mode(s) of action that may lead to adverse effects. Endocrine dismpters are addressed further in Section 4.11. 

Use of Hormones in Nonendocrine Disease. There are many examples of how various hormones and hormone-related drugs can be used to treat conditions that are not directly related to the endocrine system. For instance, certain forms of cancer respond to treatment with glucocorticoids (see Chapter 36). Drugs that block the cardiac beta-1 receptors may help control angina and hypertension by preventing excessive stimulation from adrenal medulla hormones (epinephrine, norepinephrine see Chapters 21 and 22). 

Diabetes mellitus is a disease caused by insufficient insulin secretion or a decrease in the peripheral effects of insulin. This disease is characterized by a primary defect in the metabolism of carbohydrates and other energy substrates. These metabolic defects can lead to serious acute and chronic pathologic changes. The term diabetes mellitus differentiates this disease from an unrelated disorder known as diabetes insipidus. Diabetes insipidus is caused by a lack of antidiuretic hormone (ADH) production or insensitivity to ADH. Consequently, the full terminology of diabetes mellitus should be used when referring to the insulin-related disease. Most clinicians, however, refer to diabetes mellitus as simply diabetes. ... 

Elevated levels of the hormone homocysteine, a by-product of protein digestion and metabolism, have been linked to age-related diseases such as heart disease and Alzheimer s. Research shows that by reducing our consumption of acidic protein foods, such as meat, we may be able to reduce and control our homocysteine levels. Studies have also shown that the B vitamins B6, Bi2, niacin, and folate can help lower levels of homocysteine in the blood.2... 

In recent years concerns associated with food produced with antibiotics or hormones or by biotechnology or treatment with irradiation have increased. Mad cow disease and other prion-related diseases have created great fear and economic havoc. The terrorist events of 2001 have shocked the food industry, government, and consumer into recognizing the possibility that some form of bioterrorism may be transmitted through food and water. 

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