Estradiol and Estrogen-like Alternative Therapies in Use: The Importance of the Selective and Non-Classical Actions

Abstract

Estrogen is one of the most important female sex hormones, and is indispensable for reproduction. However, its role is much wider. Among others, due to its neuroprotective effects, estrogen protects the brain against dementia and complications of traumatic injury. Previously, it was used mainly as a therapeutic option for influencing the menstrual cycle and treating menopausal symptoms. Unfortunately, hormone replacement therapy might be associated with detrimental side effects, such as increased risk of stroke and breast cancer, raising concerns about its safety. Thus, tissue-selective and non-classical estrogen analogues have become the focus of interest. Here, we review the current knowledge about estrogen effects in a broader sense, and the possibility of using selective estrogen-receptor modulators (SERMs), selective estrogen-receptor downregulators (SERDs), phytoestrogens, and activators of non-genomic estrogen-like signaling (ANGELS) molecules as treatment.

Ovariectomy-induced hormone deprivation aggravates Aβ1-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer’s disease

“…The MRI data also showed a decreased body lean ratio in the OVX groups, which may be the prodrome of a most common problem in menopausal patients, osteoporosis. Indeed, female sex hormone depletion was linked closely to low bone mineral density (94). Estrogen receptors can be also found in the bone, mediating protection of the bone structure, by inhibiting osteoclast activity and stimulating Frontiers in Endocrinology frontiersin.org development of long bones and pubic epiphyses (94)(95)(96).…”

“…Indeed, female sex hormone depletion was linked closely to low bone mineral density ( 94 ). Estrogen receptors can be also found in the bone, mediating protection of the bone structure, by inhibiting osteoclast activity and stimulating development of long bones and pubic epiphyses ( 94 – 96 ). The OVX-induced somatic changes presented in the literature were also supported by the somatic z-score, calculated from the body weight change, body fat ratio, and uterus weight.…”

Selective estrogen receptor modulators in post-menopausal osteoporosis

“…In bone, under normal conditions, 17-β-estradiol regulates osteoclast activity, stimulating osteoblast and osteocyte proliferation, and vitamin D3 and calcitonin synthesis through interaction with specific estrogen receptors (ERs) in bone, thus protecting against the risk of fractures. During puberty, estrogen contributes to the development of the pubic epiphyses and long bones [15] .…”

“…PMOP can be divided into a first period (of 3 to 5 years), in which trabecular bone loss occurs, and a second period (of 10 to 20 years), in which there is age-dependent bone loss involving not only trabecular but also cortical bone [15] .…”

Folic Acid-decorated and PEGylated Graphene Quantum Dots as efficient Tamoxifen delivery system against breast cancer cells: in vitro studies

“…On the other side, many anticancer drugs are insoluble or have poor solubility in water, with drug delivery technology and drug formulation in nanostructures, the solubility can be increased and it can be transferred to the desired places more e ciently [11]. Tamoxifen (TMX), a kind of non-steroidal selective estrogen receptor modulator (SERM), prevents cancer cell proliferation in response to estrogen in both premenopausal and postmenopausal women with ER-positive breast tumors [12]. TMX is a poorly water-soluble agent and its nanoparticles-based formulation is proposed for the enhancement of solubility and bioactivity in vivo [13].…”