Editing Selective estrogen receptor modulator (section)

== History ==
[[File:Selective estrogen receptor modulator timeline.svg|thumb|284x284px|class=skin-invert-image|Timeline of when SERMs came on the market.]]
The discovery of SERMs resulted from attempts to develop new contraceptives. [[Clomifene]] and [[tamoxifen]] prevented conception in rats but did the opposite in humans. Clomifene successfully induced ovulation in [[subfertile women]] and on February 1, 1967, it was approved in the US for the treatment of [[Ovulation#Disorders|ovulation dysfunction]] in women who were trying to conceive.<ref name="Pickar_2015">{{cite journal | vauthors = Pickar JH, Komm BS | title = Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast | journal = Post Reproductive Health | volume = 21 | issue = 3 | pages = 112–21 | date = Sep 2015 | pmid = 26289836 | doi = 10.1177/2053369115599090 | s2cid = 206825977 }}</ref> [[Toxicological]] issues prevented long term use of clomifene and further drug development for other potential applications such as [[breast cancer]] treatment and prevention.<ref name="Mirkin_2015">{{cite journal |vauthors = Mirkin S, Pickar JH|title = Selective estrogen receptor modulators (SERMs): a review of clinical data|journal = Maturitas|volume = 80|issue = 1|pages = 52–7|date = Jan 2015|pmid = 25466304|doi = 10.1016/j.maturitas.2014.10.010}}</ref>

It was another ten years before tamoxifen was approved in December 1977, not as a contraceptive but as a hormonal treatment to treat and prevent breast cancer.<ref name="Mirkin_2015" /> The discovery in 1987 that the SERMs tamoxifen and [[raloxifene]], then thought to be [[antiestrogen]]s because of antagonist effects in breast tissue, showed estrogenic effects in preventing bone loss in [[ovariectomized rat]]s had a great effect on our understanding of the function of estrogen receptors and [[nuclear receptor]]s in general.<ref name="Miller_2002">{{cite journal | vauthors = Miller CP | title = SERMs: evolutionary chemistry, revolutionary biology | journal = Current Pharmaceutical Design | volume = 8 | issue = 23 | pages = 2089–111 | year = 2002 | pmid = 12171520 | doi = 10.2174/1381612023393404 }}</ref> The term SERM was introduced to describe these compounds that have a combination of estrogen [[agonist]], partial agonist, or antagonist activities depending on the tissue.<ref name="Pickar_2015" /> Toremifene has been shown to be compatible with tamoxifen, and in 1996 it was approved for use in the treatment of breast cancer in postmenopausal women.<ref>{{cite web | publisher = European Medicines Agency (EMA) | title = Fareston | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000091/human_med_000785.jsp&mid=WC0b01ac058001d124 | access-date = 2015-11-02 | archive-date = 2018-06-20 | archive-url = https://web.archive.org/web/20180620172935/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F000091%2Fhuman_med_000785.jsp&mid=WC0b01ac058001d124 | url-status = dead }}</ref>

Raloxifene originally failed as a breast cancer drug due to its poor performance in comparison to tamoxifen in the laboratory<ref name="Musa_2007">{{cite journal |vauthors = Musa MA, Khan MO, Cooperwood JS|title = Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs)|journal = Current Medicinal Chemistry|volume = 14|issue = 11|pages = 1249–61|year = 2007|pmid = 17504144|doi = 10.2174/092986707780598023}}</ref> but the estrogenic effects of raloxifene on bone led to its rediscovery and approval in 1997.<ref name="Mirkin_2015" /> It was approved for prevention and treatment of osteoporosis and was the first clinically available SERM to prevent both osteoporosis and breast cancer.<ref name="Miller_2002" /> [[Ospemifene]] was approved on February 26, 2013, for the treatment of moderate to severe [[dyspareunia]], which is a symptom, due to [[menopause]], of vulvar and vaginal [[atrophy]]. Combined therapy with [[conjugated estrogen]]s and the SERM [[bazedoxifene]], was approved on October 3, 2013, for the treatment of [[vasomotor symptoms]] linked with menopause. Bazedoxifene is also used in the prevention of postmenopausal osteoporosis.<ref name="Mirkin_2015" /> The search for a [[Potency (pharmacology)|potent]] SERM with bone efficacy and better bioavailability than raloxifene led to the discovery of lasofoxifene.<ref name="Rosano_2011">{{cite journal | vauthors = Rosano C, Stec-Martyna E, Lappano R, Maggiolini M | title = Structure-based approach for the discovery of novel selective estrogen receptor modulators | journal = Current Medicinal Chemistry | volume = 18 | issue = 8 | pages = 1188–94 | year = 2011 | pmid = 21291367 | doi = 10.2174/092986711795029645 }}</ref> Although lasofoxifene was approved in 2009, it was not marketed for three years following the approval, so the marketing authorization for it has expired.<ref>{{cite web | title = Fablyn | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000977/human_med_000783.jsp&mid=WC0b01ac058001d124 | publisher = The European Medicines Agency (EMA) | access-date = 2015-11-02 | archive-date = 2018-02-12 | archive-url = https://web.archive.org/web/20180212201605/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F000977%2Fhuman_med_000783.jsp&mid=WC0b01ac058001d124 | url-status = dead }}</ref> In Europe, bazedoxifene is indicated for the treatment of osteoporosis in postmenopausal women at increased risk of fracture. In India, [[ormeloxifene]] has been used for [[dysfunctional uterine bleeding]] and birth control.<ref name="Mirkin_2015" />