No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Control of Carbohydrate Metabolism in Menopausal Women Receiving Transdermal Estrogen Therapy
Almost all of the epidemiological studies on the consequences of estrogen replacement treatment (ERT) refer to subiects treated with orai conjugated equine estrogens (CEE). These studies suggest that breast cancer (BC) risk is limited and can only be seen after long-term and/or high dosage use. Orally adrninistered estrogens present a number of metabolic and endocrine peculiarities, some of which could be important in reducing the risk to the breast, Actually, these peculiarities are opposite to those observed in post-menopausal women with abdominal obesity (AO), a group which has recently been identified to be at high risk. AO (as other situations in which an in-crcasc in BC risk does exist) shows a scx-hormone-binding-globulin(SHBG) level reduction, which causes an increase of both estrogenic and androgenic activity. Further features of AO, possibly involved in BC risk, could be: i) increased free fatty acid (FFA) levels; ii) hyperinsulinemia; iii) increase of circulating insulin-like growth-factor-I (IGF-I) activity. On the contrary oral estrogens, through their hepatocellular effects, cause: i) a cIearcut SHBG increase; ii) a trcnd to reduced circulating IGF-I activity. As a consequence, the possibility that oral estrogens are characterized by a favourable balance between cstrogenic activity and biological modifications protective to the breast, is worth considcration. Even non-oral estradiol have a possible protective action through FFA leve! reduction; however, due to the abscnce of hepatocellular effect, it does not influence SHBG levels and IGF-I activity. It secms difficult to extend data on the relationship between BC and orai CEE to other types of types of ERT. For the latter, further study will be necessary.
Almost all of the epidemiological studies on the consequences of estrogen replacement treatment (ERT) refer to subiects treated with orai conjugated equine estrogens (CEE). These studies suggest that breast cancer (BC) risk is limited and can only be seen after long-term and/or high dosage use. Orally adrninistered estrogens present a number of metabolic and endocrine peculiarities, some of which could be important in reducing the risk to the breast, Actually, these peculiarities are opposite to those observed in post-menopausal women with abdominal obesity (AO), a group which has recently been identified to be at high risk. AO (as other situations in which an in-crcasc in BC risk does exist) shows a scx-hormone-binding-globulin(SHBG) level reduction, which causes an increase of both estrogenic and androgenic activity. Further features of AO, possibly involved in BC risk, could be: i) increased free fatty acid (FFA) levels; ii) hyperinsulinemia; iii) increase of circulating insulin-like growth-factor-I (IGF-I) activity. On the contrary oral estrogens, through their hepatocellular effects, cause: i) a cIearcut SHBG increase; ii) a trcnd to reduced circulating IGF-I activity. As a consequence, the possibility that oral estrogens are characterized by a favourable balance between cstrogenic activity and biological modifications protective to the breast, is worth considcration. Even non-oral estradiol have a possible protective action through FFA leve! reduction; however, due to the abscnce of hepatocellular effect, it does not influence SHBG levels and IGF-I activity. It secms difficult to extend data on the relationship between BC and orai CEE to other types of types of ERT. For the latter, further study will be necessary.
After physiological or surgical menopause, women are suddenly deficient in their main estrogenic hormone, 17 beta-estradiol. Only a very small amount of estradiol is still produced from adrenal precursors. More than 50 per cent of all postmenopausal women suffer for varying periods of time from the symptoms of this estrogen deficiency, most notably vasomotor instability (hot flashes) and sleep disturbances. The trophic symptoms of estrogen deficiency have longer lasting and cumulative consequences: accelerated loss of bone density that eventually increases the risk of fractures, genitourinary atrophy resulting in dyspareunia and urinary atrophy; and lipoprotein changes with increased risk of coronary heart morbidity and mortality. Today estrogen deficiency is mainly treated by oral estrogens--either conjugated equine estrogens or estradiol--in milligram doses far in excess of what would be required by the parenteral route. Taken orally, estradiol is largely transformed to estrone through metabolism in the liver. Certain undesirable side effects of estrogen therapy (e.g., increased renin substrate) are caused by the unphysiologic nature of the oral route of administration. Dosage forms for parenteral estrogen administration have been widely studied: vaginal or percutaneous creams, intranasal solutions, and sublingual tablets. All of these result in a pronounced, transient elevation of plasma concentrations of estradiol and a minor increase of estrone. An improved regimen, which produces more constant plasma concentrations, is achieved with an experimental estradiol implant or with a vaginal ring delivering estradiol. These studies demonstrate that daily estradiol doses of 0.2 mg and less are effective in reducing hot flashes. Effective doses of conjugated estrogens and estradiol administered by different routes achieve estradiol plasma concentrations of similar magnitude (between 35 and 100 pg/ml). Estrone plasma levels vary widely with these different regimens and do not seem to be directly related to efficacy. In summary, the literature indicates that efficacy of estrogen replacement for the treatment of the menopausal symptoms appears to relate to the magnitude of estradiol plasma levels; effective therapy is achieved by an estradiol regimen that maintains plasma estradiol levels of at least 35-55 pg/ml. Efficacy of estrogens in the prevention of osteoporosis as assessed by densitometry has been demonstrated for conjugated oral estrogens.(ABSTRACT TRUNCATED AT 400 WORDS)
The effect of hormone replacement therapy on carbohydrate metabolism in menopausal women is briefly reviewed. Estrogen treatment has bi-phasic effect; abnormal glucose tolerance with a normal insulin level is commonly found within 3 months of treatment, followed by normalization of the glycemia when treatment is extended beyond one year. Normal tolerance usually occurs once treatment is stopped. Estrogens may therefore be regarded as being glucogenic (reversible blood glucose elevation) rather than diabetogenic (permanent hyperglycemia). With some exceptions, progestogens have little effect on glucose tolerance within the first 3-6 months of treatment; thereafter progressive hyperglycemia and hyperinsulinemia occur. Postulated mechanisms for the hormonal effect on carbohydrate metabolism are noted, including the possible synergistic effect of estrogens on progestogen glucogenic activity. The significance of chronic hyperglycemia and vascular disease is commented upon.