Nath Anita, Sitruk-Ware Regine
Tietze fellow from the Population Council, New York, NY 10065, USA.
Eur J Contracept Reprod Health Care. 2009 Apr;14(2):88-96. doi: 10.1080/13625180902747425.
New options for hormonal replacement therapy (HRT) include non-oral, low-dose sustained delivery of progestins in different formulations. Since the Women's Health Initiative (WHI) study, prescription trends were observed selecting progesterone over other progestins, or delivering the progestin parenterally, in order to reach low systemic levels of the steroid. Such modalities include progesterone vaginal rings or gels, and intra-uterine systems (IUSs). When given via the transdermal and intranasal routes, the hormones are delivered systemically although the first liver impact is by-passed. Of the progestins selected for delivery of low doses by means of an IUS, or transdermally, only very active molecules can be used. An IUS approved for HRT in several countries delivers very low doses of levonorgestrel (LNG) in the uterine cavity. Nestorone is well absorbed transdermally from a gel as well as from a metered dose transdermal system (MTDS) that sprays an invisible film on the skin. Transdermal patches combining oestradiol with either norethisterone acetate or LNG have been available for several years. Although parenteral administration of progesterone or low-dose progestins should in theory be associated with fewer side-effects than oral therapy, the long-term safety of the newer systems warrants further evaluation.
激素替代疗法（HRT）的新选择包括以不同剂型非口服、低剂量持续递送孕激素。自妇女健康倡议（WHI）研究以来，观察到处方趋势为选择黄体酮而非其他孕激素，或通过肠胃外途径递送孕激素，以实现类固醇的低全身水平。这些方式包括黄体酮阴道环或凝胶，以及宫内系统（IUS）。通过透皮和鼻内途径给药时，激素会全身递送，尽管绕过了肝脏的首过效应。对于通过IUS或透皮方式递送低剂量的孕激素，只能使用活性非常高的分子。在多个国家被批准用于HRT的一种IUS可在子宫腔内递送极低剂量的左炔诺孕酮（LNG）。从凝胶以及向皮肤上喷洒无形薄膜的定量透皮系统（MTDS）中，奈司孕酮可很好地经皮吸收。结合雌二醇与醋酸炔诺酮或LNG的透皮贴剂已经上市数年。尽管理论上肠胃外给予黄体酮或低剂量孕激素应比口服疗法副作用更少，但新系统的长期安全性仍需进一步评估。
