Background:

Estradiol, or 17β-estradiol, is a steroid and estrogen sex hormone, and the primary female sex hormone. It is named for and is important in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is essential for the development and maintenance of female reproductive tissues but it also has important effects in many other tissues including bone. β-Estradiol-d3 is the deuterated β-estradiol.

In vitro: Addition of β-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. β-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria [1].

In vivo: It was found that the density of synapses in the stratum radiatum of the hippocampal CA1 region in the adult female rat is sensitive to β-estradiol manipulation and fluctuates naturally as the levels of ovarian steroids vary during the 5 d estrous cycle. Synapse density then appears to cycle back to proestrus values over a period of several day [2].

Clinical trial: The combined regimen of β-estradiol and norethisterone acetate in postmenopausal Thai women was more effective in relieving the climacteric symptoms in women who used the drug than those who used the placebo. There was a high incidence of amennorhoea after 12 months. But there was also a high frequency of abnormal bleeding in the first 3 months of treatment. Counseling on the bleeding pattern and common side effects should be conducted before starting the treatment to increase the compliance [3].

Reference:
[1] Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Williams DC, Manolagas SC.  17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest. 1992 Mar;89(3):883-91.
[2] Woolley CS, McEwen BS.  Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci. 1992 Jul;12(7):2549-54.
[3] Limpaphayom KK, Bunyavejchevin S.  Clinical effects of 17 beta-estradiol and norethisterone acetate in postmenopausal Thai women. J Med Assoc Thai. 2000 Apr;83(4):407-16.
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