Pluchino N, Genazzani A D, Bernardi F, Casarosa E, Pieri M, Palumbo M, Picciarelli G, Gabbanini M, Luisi M, Genazzani A R
Division of Obstetrics and Gynecology, University of Pisa, Italy.
Gynecol Endocrinol. 2005 Mar;20(3):144-9. doi: 10.1080/09513590400021169.
The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the androgen deficiency syndrome in postmenopausal women.
本研究的目的是评估替勃龙（2.5毫克）、经皮雌二醇（50微克）（TE）以及不同的口服雌激素 - 孕激素方案，即结合马雌激素（0.625毫克）加醋酸甲羟孕酮（5毫克）（CEE + MPA）和雌二醇（2毫克）加醋酸炔诺酮（1毫克）（E2 + NETA）对健康绝经后女性循环雌二醇、孕酮、别孕烷醇酮、皮质醇和脱氢表雄酮（DHEA）水平的影响。在85名绝经后女性治疗的第1、3、6和9个月前后采集血样。治疗1个月后，TE、CEE + MPA和E2 + NETA组的雌二醇水平升高（p < 0.001），但替勃龙组在整个随访期间未发生变化。E2 + NETA和替勃龙治疗在治疗1年后均导致孕酮水平升高（p < 0.05）。所有基于雌激素的组中别孕烷醇酮水平均升高，治疗3个月后显著升高（p < 0.01）。接受替勃龙治疗的患者在3个月时别孕烷醇酮水平显著升高（p < 0.05），但低于其他组。TE组和CEE + MPA组分别在治疗6个月和12个月后皮质醇水平显著降低。替勃龙和E2 + NETA治疗均未改变循环皮质醇水平。TE或雌激素 - 孕激素治疗6个月后，无论所用孕激素的存在与否或类型如何，DHEA水平均显著降低（p < 0.05）。相比之下，替勃龙治疗12个月期间DHEA水平保持稳定。别孕烷醇酮是一种具有镇静和抗焦虑特性的类固醇，对这些不同治疗的反应性升高可能至少部分地解释了激素替代疗法和替勃龙对焦虑、情绪和行为的中枢效应。与基于雌激素的疗法不同，替勃龙治疗不会降低绝经后的DHEA环境，因此不会加重绝经后女性的雄激素缺乏综合征。
