Evaluates evidence for an increased risk of cancer in women using combined oral contraceptives, progestogen-only hormonal contraceptives, post-menopausal estrogen therapy, and post-menopausal estrogen-progestogen therapy. Although the carcinogenicity of these preparations has been extensively investigated, the book stresses the many complex methodological issues that must be considered when interpreting findings and weighing results. Evidence of an association between use of these preparations and positive effects on health, including a reduced risk of some cancers, is also critically assessed. The first and most extensive monograph evaluates evidence of an association between the use of combined oral contraceptives and cancer at nine sites. Concerning breast cancer, the evaluation concludes that, even if the association is causal, the excess risk for breast cancer associated with patterns of use that are typical today is very small. Studies of predominantly high-dose preparations found an increased risk of hepatocellular carcinoma in the absence of hepatitis viruses. Citing these findings, the evaluation concludes that there is sufficient evidence in humans for the carcinogenicity of combined oral contraceptives. The evaluation also found sufficient evidence for the carcinogenicity of some, but not all, combined preparations in animals. Combined oral contraceptives were classified as carcinogenic to humans. The evaluation also cites conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium. Progestogen-only contraceptives are evaluated in the second monograph, which considers the association with cancer at six sites. The evaluation found no evidence of an increased risk for breast cancer. Although the evaluation found sufficient evidence in animals for the carcinogenicity of medroxyprogesterone acetate, evidence for the carcinogenicity of progestogen-only contraceptives in humans was judged inadequate. Progestogen-only contraceptives were classified as possibly carcinogenic to humans. The third monograph, on post-menopausal estrogen therapy, considers evidence of an association with cancer at eight sites. Findings from a large number of epidemiological studies indicate a small increase in the risk of breast cancer in women who have used these preparations for five years or more. Studies consistently show an association between use of post-menopausal estrogen therapy and an increased risk for endometrial cancer. Data on the association with other cancers were either inconclusive or suggested no effect on risk. The evaluation concludes that post-menopausal estrogen therapy is carcinogenic to humans. The final monograph evaluates the association between the use of post-menopausal estrogen-progestogen therapy and cancer at four sites. The evaluation of limited data on breast cancer found an increased relative risk observed with long-term use. Data were judged insufficient to assess the effects of past use and of different progestogen compounds, doses, and treatment schedules. For endometrial cancer, the evaluation found an increase in risk relative to non-users when the progestogen was added to the cycle for 10 days or fewer. Post-menopausal estrogen-progestogen therapy was classified as possibly carcinogenic to humans. Concerning post-menopausal therapy in general, the book notes that evidence of carcinogenic risks must be placed in perspective of potential benefits. The prevention of osteoporotic fractures is cited as the best-established benefit. Evidence also suggests that estrogen prevents heart disease and may prevent memory loss and dementia.

Either deficient or excessive hormone production has been observed with respect to some rather bizarre clinical manifestations. Starting with the synthesis or isolation of pure hormones in the early 30s, estrogens (the female sex hormones) and androgens (the male sex hormones) have become readily available for clinical and other uses and their physiologic activity has been intensively studied. The relationship between hormones and cancer was perhaps one of the earliest research areas in cancer. In the early work of the 20s it was clearly shown in experimental animals that under certain conditions both endogenous and exogenous hormones could induce certain cancers and tumors. More recently, attention has been focused on the use of androgenic anabolic steroids by athletes as body builders and the widescale multiple use of estrogens in terms of carcinogenic hazard. Most striking in recent years are the potential adverse effects of estrogens relevant to sterility, gall bladder disease, and neoplasia. The pervasive environmental hazard contributed by estrogens may arise from variant sources. Such sources may be: (a) endogenous hormones, (b) estrogenic compounds occurring naturally in foods or as fungal con taminants in food stuffs, ( c) estrogens added to livestock feed, (d) estrogenic additives to cosmetics, (e) oral contraceptives, and (f) estrogens used clinically for threatened abortions, lactation suppres sion, menstrual anomalies, and therapeutic treatment of certain forms of cancer.

In the past decade there has been a growing public interest and resurgence in research in the field of hormonal carcinogenesis. This is due to the widespread use of therapeutic hormonal agents worldwide and to the increasing awareness of the causal association of hormones, both endogenous and exogenously administered, and a variety of human cancers. These associations include estrogens in uterine, cervical, vaginal, liver, testicular, prostatic, and possible breast cancers; progesterone and progestational hormones in breast cancer; androgens and anabolic steroids in hepatic and prostatic cancers. Additionally, gonadotrophins playa role in the etiology of ovarian and testicular cancers and thyroid-stimulating hormones in thyroid cancers. Therefore, hormonal carcinogenesis encompasses the study of both natural and synthetic hormonal agents, including growth factors and other peptide and protein factors, which contribute substantially to the etiology of both human and animal neoplasms, benign or malignant. Hormones may be involved in all aspects of neoplastic transformation, including initiation, promotion, and progression, and the inhibition of these processes. There are a number of important issues in women's health that need to be addressed. More than 40 million U. S. women are menopausal, and these women have a life expectancy of over 30 years after the menopause. When these figures are multiplied worldwide, the numbers become staggering. After the menopause, estrogen replacement therapy (ERT) is the choice of most women in industrialized countries.

These conference proceedings reflect the resurgence of public awareness and research interest in the field of hormonal carcinogenesis, a phenomenon that is largely the result of the widespread use of therapeutic hormonal agents and the causal association of hormones and a variety of cancers, such as breast, prostatic, unterine and cervical. Significant attention is paid to the popular use of oestrogen therapies in women's health care.

Since our previous symposium in 1995, the pace of research in hormones and cancer has accelerated. Progress in our understanding of hormonal carcinogenic processes has been a direct result of the advances made in cell biology, endocrinology, and carcinogenesis at the molecular level. The newer fields of molecular genetics and cytogenetics already have and are expected to continue to playa major role in furthering our understanding of the cellular and molecular events in hormonal carcinogenesis. It has become increasingly clear that the risk of naturally occurring sex hormones in carcinogenic processes, both in human and in animal models, requires only minute quantities of hormones, at both the serum and tissue levels. Moreover, hormone target tissues for neoplastic transformation, perhaps with the exception of the liver, generally have relatively modest ability to metabolize sex hormones, such as the breast and prostate. Table 1 summarizes the serum, and in most cases, the tissue levels of sex hormones, both endogenously and exogenously ingested, which are associated with increased risk for endocrine-associated cancers such as breast, endometrium, and prostate, as well as the hormone levels of four experimental models that have been shown to elicit high tumor incidences. In contrast to the human, in which the hormone levels are cyclic, however, the latter require continuous hormone exposure at these relatively low levels.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together provide important insights to our understanding of hormonal cancer causation, development, and prevention; the primary objective of these Symposia. A special emphasis is placed on the two major endocrine-related cancers, that is, breast and prostate. The emerging fields of colon, lung, and pancreatic cancers in relation to hormones are examined.

In the past decade there has been a growing public interest and resurgence in research in the field of hormonal carcinogenesis. This is due to the widespread use of therapeutic hormonal agents worldwide and to the increasing awareness of the causal association of hormones, both endogenous and exogenously administered, and a variety of human cancers. These associations include estrogens in uterine, cervical, vaginal, liver, testicular, prostatic, and possible breast cancers; progesterone and progestational hormones in breast cancer; androgens and anabolic steroids in hepatic and prostatic cancers. Additionally, gonadotrophins playa role in the etiology of ovarian and testicular cancers and thyroid-stimulating hormones in thyroid cancers. Therefore, hormonal carcinogenesis encompasses the study of both natural and synthetic hormonal agents, including growth factors and other peptide and protein factors, which contribute substantially to the etiology of both human and animal neoplasms, benign or malignant. Hormones may be involved in all aspects of neoplastic transformation, including initiation, promotion, and progression, and the inhibition of these processes. There are a number of important issues in women's health that need to be addressed. More than 40 million U. S. women are menopausal, and these women have a life expectancy of over 30 years after the menopause. When these figures are multiplied worldwide, the numbers become staggering. After the menopause, estrogen replacement therapy (ERT) is the choice of most women in industrialized countries.

Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.

In this sobering work, a respected medical writer and researcher warns women not to be too hasty in embracing estrogen replacement therapy, which so many doctors are now recommending with great enthusiasm. A careful, cautionary book that will stir controversy--and may save lives.

Sex Hormones not only regulate reproductive function, but they also play a prominent role in the biology and physiology of several organs/tissues and in the pathophysiology of several diseases. During the last two decades, the information on the mechanisms of action of sex hormones, such as estrogens and androgens, has rapidly evolved from the conventional nuclear receptor dependent mechanisms to include additional non-nuclear, non-genomic and receptor-independent mechanisms. This highlights the need to update the current knowledge on sex hormones and their mode of action. Increasing evidence that exogenous/epigenetic factors can influence sex hormone production and action highlights the need to update our knowledge on the mechanisms involved. This book provides a systematic and updated overview of the male/female sex-hormones and their impact in the biology and physiology of various organs. Additionally, the book discusses their positive and negative association with the pathophysiology of various diseases (e.g. osteoporosis, cardiovascular-disease, hypogonadism, reproduction, cancer) and their therapeutic potential.