Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment

Melis, Gian Benedetto; Piras, Bruno; Marotto, Maria Francesca; Orrù, Marisa; Maricosu, Giovanni; Pilloni, Monica; Guerriero, S.; Angiolucci, Marco; Lello, Stefano; Paoletti, Anna Maria

doi:10.1517/17425255.2012.695775

Cited by 30 publications

(21 citation statements)

References 56 publications

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“…Clinical trials for selective ER modulators have not been successful. Selective PR modulators have not yet been approved in the United States; however, in Europe, use of ulipristal acetate was approved in 2012 (48), and has been shown to reduce leiomyoma volume and leiomyoma-associated pain (47). An adverse effect of the selective PR modulators is the effect on the endometrium termed as PAEC (PR-associated endometrial changes), an effect that spontaneously reverses at cessation of treatment (43,44,47).…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

Malik

Britten

Cox

et al. 2016

Fertility and Sterility

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This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy.

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Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

Malik

Britten

Cox

et al. 2016

Fertility and Sterility

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“…In all studies inclusion criteria was age 18-50 years with fibroid related menorrhagia and anemia and uterus size=/<16 wks pregnant uterus size with atleast one fibroid 3 cm or more and largest 10 cm in diameter as seen by MRI, blood loss >100 ml (d1-8, pictorial blood assessment chart (PBAC), significant haemoglobin decrease if <10.2 gm without macrocytosis [41,42] . Since 3 months use was found efficacious for preoperative symptomatic fibroids in controlling excessive bleeding and hence normalizing anaemia, decrease uterine fibroid size and volume for upto 6 months and thus quality of life initially UPA got a license in Europe and Canada in a dose of 5 mg for preoperative before surgery [43] . SPRM administration has been shown to lead to a pattern of benign, nonphysiologic, nonproliferative histologic features of endometrium known as progesterone receptor modulator associated endometrial changes(PAEC) [44,45] .…”

Section: Role Of Ulipristal Acetatementioning

confidence: 99%

Medical Management of leipmyomas-emphasis for different geographical regions

KocharKaur¹

2015

JGNB

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Leiomyomas are the common benign tumours of uterus. Surgery is the most common mode of treatment of symptomatic fibroids. With the advent of minimally invasive interventional procedures like uterine artery embolization (UAE), and focused ultrasound on MRI we got some lesser invasive techniques, although they have drawbacks regarding ovarian reserve etc for patients desiring fertility. Initially GnRH agonists like leuprolide acetate were the most effective medical agents introduced, but their drawback was bone density demineralization, hot flushes on long term use besides cost. Selective progesterone receptor modulators gradually got introduced with initial trials with mifepristone (RU486), followed by asoprisnil, ulipristalacetate. Since mifepristone had antiglucocorticoid and androgen receptor activity it was not approved by FDA for license, while four PEARL trials have got completed for UPA acetate 5&10mg regarding safety and efficacy and intermittent therapy with 5mg got FDA approval in Europe and Canada before surgery. Further trials indicated it may be the future drug of choice for patients desiring fertility for long term intermittent therapy and possibly avoiding surgery and its complications like adhesions, uterine scar and risk for rupture during pregnancy. However in countries where uripristal is not available still one is forced to use mifepristone. Detailed mechanism of all these drugs is discussed and a case report of a young unmarried girl with high BMI is reported where mifepristone intermittent was effective not only in relieving patients symptoms but effective in decreasing uterine and fibroid volume which highlights how in such young cases one can preserve future fertility without putting them at risk of surgery and sometimes myomectomy complications ending in hysterectomy.

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“…These steroids bind to PR and GR but showed lower antiprogestational and antiglucocortocoid activity than 12; however, they did not exhibit any agonistic activity 28 . In addition, 14 has been studied as an alternative treatment for uterine fibroids (leiomyomata) and the results of a successfully completed phase III clinical trial with 14 have been published 29 . The administration of 5 or 10 mg/daily of this compound induced a rapid decrease of bleeding; it also reduced the size of the fibroids by 50% and restored the quality of women's life 30 .…”

Section: Gnucleousmentioning

confidence: 99%

Recent advances in structure of progestins and their binding to progesterone receptors

Cabeza

Heuze

Sánchez

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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The role of progesterone in women's cancers as well as the knowledge of the progesterone receptor (PR) structure has prompted the design of different therapies. The aim of this review is to describe the basic structure of PR agonists and antagonists as well as the recent treatments for illness associated with the progesterone receptor. The rational design for potent and effective drugs for the treatment of female cancer must consider the structural changes of the androgen and progestogen skeleton which are an indicator of their activity as progestins or antiprogestins. The presence of a hydroxyl group at C-17 in the progesterone skeleton brings about a loss of progestational activity whereas acetylation induces a progestational effect. The incorporation of an ethynyl functional group to the testosterone framework results in a loss of androgenic activity with a concomitant enhancement of the progestational effect. On the other hand, an ester function at C-3 of dehydroepiandrosterone skeleton induces partial antagonism to the PR.

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Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment

Cited by 30 publications

References 56 publications

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

Medical Management of leipmyomas-emphasis for different geographical regions

Recent advances in structure of progestins and their binding to progesterone receptors

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