Generatie I I. Godefridus Jacobs, ovl. Uit deze relatie 4 zonen: 1. Joannis, ged. RK te Meerssen op , ovl. Gerardus, geb.
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This article has been cited by other articles in PMC. Abstract Although the menopause is a generic physiologic event, its biology is variable and specific to a given individual. Advances in molecular biology have led to the development of newer pharmacologic agents that are tailored to meet specific therapeutic objectives, based on the hormonal biology of relevant organs.
Tibolone, an analogue of the progestin, norethynodrel, is a drug with tissue-specific effects on receptors and enzymes that influences the synthesis and metabolism of endogenous estrogen, progesterone, and androgen.
The postmenopausal synthesis and metabolism of estrogen and androgen are briefly reviewed with particular reference to sex steroid activity in various target organs. On the basis of this hormonal physiology, the clinical utility of tibolone is reviewed as a therapeutic agent for the treatment of the symptomatic menopause. The effects of tibolone on bone health and osteoporosis, cardiovascular disease, the breast, and the endometrium are summarized, and its role in clinical practice is reviewed.
The reason for this discrepancy is clear; although the menopause is a generic physiologic event, its biology is variable and specific to the individual woman. The net effect of exogenous therapy including HT will further be influenced by the age and health of the individual and hence the timing of the intervention plus the dose and the route of administration and therefore the pharmacokinetics of the prescribed treatment.
In this context, postmenopausal HT is additive to endogenously synthesized estrogen and androgens, and is best regarded as pharmacologic therapy. Drugs can be tailored to meet specific therapeutic objectives while avoiding undesirable side effects. Thus, diminishing function of certain hormone-dependent tissues — such as bone — can be upregulated pharmacologically by compounds that target receptors and enzymes responsible for local estrogen synthesis in bone, and not in other estrogen-dependent tissues, such as the endometrium and breast.
Tibolone is a drug that satisfies this latter category. This article briefly reviews the hormonal biology of relevant organs, the modulating pharmacologic effect of tibolone and its clinical utility in the treatment of the symptomatic menopause, and some prevalent postmenopausal conditions: osteoporosis, cardiovascular disease, and breast and endometrial cancer.
Hormonal Biology Hormone Synthesis The pathways of estrogen biosynthesis and metabolism [6 — 8] are summarized in Figure 1. The primary source of the substrate for estrogen is the adrenal gland; ovarian androgens also serve as precursors but play a more minimal role.
Aromatization of testosterone to estradiol is the main bioconversion pathway and takes place in extragonadal tissues, muscle, adipose tissue, breast, bone, brain and vascular endothelium and smooth muscle. Aromatization of androgen to estrogen increases with aging. The net result is the postmenopausal change in dominance of the two estrogens with a reduction of the E2 to E1 ratio to less than 1.
There is an overall decrease in the total amount of estrogen synthesized, the degree of which varies among individuals. The expression of the steroid-converting enzymes differs in and between the tissues of menopausal women, resulting in individualized tissue-selective metabolism.
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