Nugent Ailish G, Leung Kin-Chuen, Sullivan David, Reutens Anne T, Ho Ken K Y
Garvan Institute of Medical Research, Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Clin Endocrinol (Oxf). 2003 Dec;59(6):690-8. doi: 10.1046/j.1365-2265.2003.01907.x.
Oral but not transdermal oestrogen administration reduces IGF-I, and increases GH binding protein (GHBP) reflecting effects on hepatic endocrine function in postmenopausal women. As progestogens attenuate the effects of oestrogen on circulating lipid levels according to their androgenic properties, we have investigated the impact of progestogen types on the hepatic endocrine effects of oestrogen.
Four progestogens differing in androgenicity were co-administered in a monthly cyclical regimen in random order to postmenopausal women receiving either oral (n = 9, premarin 1.25 mg) or transdermal (n = 10, Estraderm 100 microg patches twice weekly). The four progestogens were cyproterone acetate (CA 5 mg, antiandrogenic), dydrogesterone (20 mg, neutral), medroxyprogesterone acetate (MPA 10 mg, mildly androgenic), norethisterone (2.5 mg, androgenic).
Nineteen postmenopausal women (age 57 +/- 3 years, mean +/- SE) were studied.
The effects of oestrogen alone and the combined effects with each progestogen type on IGF-I, GHBP, SHBG, cholesterol, triglycerides and lipoprotein(a) were investigated.
Mean IGF-I fell while GHBP and SHBG levels increased with oral (P < 0.01) but not transdermal oestrogen administration. When the combined effects were examined, progestogens did not affect IGF-I, GHBP and SHBG during oral oestrogen treatment, while they significantly increased (P < 0.01) mean IGF-I levels during transdermal therapy. Among the progestogen types, only norethisterone prevented the fall in IGF-I induced by oral oestrogen. During transdermal therapy, MPA and norethisterone but not CA or dydrogesterone significantly increased (P < 0.005) IGF-I. The rise in GHBP induced by oral oestrogens tended to be lower during co-administration of MPA and norethisterone. The increase in SHBG induced by oral oestrogen was attenuated (P < 0.05) by norethisterone which was the only progestogen that lowered SHBG (P < 0.05) during transdermal oestrogen treatment. Mean IGF-I was higher (P < 0.001), GHBP and SHBG lower during co-administration of androgenic progestogens (MPA and norethisterone).
Oestrogen effects on IGF-I, GHBP and SHBG are dependent on the route of administration with progestogens having variable effects. Among the progestogen types, norethisterone, the most androgenic, had the greatest effect, particularly on IGF-I. Progestogens modulate the effects of oestrogen on hepatic endocrine function in relation to their intrinsic androgenic properties. The modulatory effects of progestogens on IGF-I during oestrogen therapy may have long-term implications for lean body mass.
口服而非经皮给予雌激素可降低绝经后女性的胰岛素样生长因子-I（IGF-I），并增加生长激素结合蛋白（GHBP），这反映了对肝脏内分泌功能的影响。由于孕激素根据其雄激素特性会减弱雌激素对循环脂质水平的影响，我们研究了孕激素类型对雌激素肝脏内分泌作用的影响。
将四种雄激素活性不同的孕激素以每月周期性方案随机序贯给予接受口服（n = 9，结合雌激素1.25 mg）或经皮（n = 10，雌二醇透皮贴剂100 μg，每周两次）治疗的绝经后女性。这四种孕激素分别是醋酸环丙孕酮（CA 5 mg，抗雄激素）、地屈孕酮（20 mg，中性）、醋酸甲羟孕酮（MPA 10 mg，轻度雄激素）、炔诺酮（2.5 mg，雄激素）。
研究了19名绝经后女性（年龄57±3岁，均值±标准误）。
研究了单独雌激素以及与每种孕激素类型联合使用对IGF-I、GHBP、性激素结合球蛋白（SHBG）、胆固醇、甘油三酯和脂蛋白(a)的影响。
口服雌激素时，平均IGF-I下降，而GHBP和SHBG水平升高（P < 0.01），经皮给予雌激素则无此现象。在检查联合作用时，口服雌激素治疗期间孕激素不影响IGF-I、GHBP和SHBG，而在经皮治疗期间它们显著升高（P < 0.01）平均IGF-I水平。在孕激素类型中，只有炔诺酮可防止口服雌激素引起的IGF-I下降。在经皮治疗期间，MPA和炔诺酮而非CA或地屈孕酮显著升高（P < 0.005）IGF-I。MPA和炔诺酮联合给药期间，口服雌激素诱导的GHBP升高趋势较低。口服雌激素诱导的SHBG升高被炔诺酮减弱（P < 0.05），炔诺酮是经皮雌激素治疗期间唯一降低SHBG（P < 0.05）的孕激素。雄激素性孕激素（MPA和炔诺酮）联合给药期间，平均IGF-I较高（P < 0.001），GHBP和SHBG较低。
雌激素对IGF-I、GHBP和SHBG的作用取决于给药途径，孕激素有不同作用。在孕激素类型中，雄激素性最强的炔诺酮作用最大，尤其是对IGF-I。孕激素根据其内在雄激素特性调节雌激素对肝脏内分泌功能的作用。雌激素治疗期间孕激素对IGF-I的调节作用可能对瘦体重有长期影响。
