Ulipristal acetate how does it work

Sex in Australia: Reproductive experiences and reproductive health among a representative sample of women. Available at www. Long-term medical management of uterine fibroids with ulipristal acetate.

Fertil Steril ; 1 — Final decisions and reasons for decisions by delegates of the Secretary to the Department of Health 27 October Canberra: Commonwealth of Australia, Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens. Ulipristal acetate versus levonorgestrel for emergency contraception: A randomised non-inferiority trial and meta-analysis.

London: FSRH, Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing. Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception. Contraception ;91 2 — Can we identify women at risk of pregnancy despite using emergency contraception?

Data from randomized trials of ulipristal acetate and levonorgestrel. Emergency contraception. Fertility awareness methods. Sydney: Bayer, BMJ ;— Application of a method for estimating day of ovulation using urinary estrogen and progesterone metabolites.

Epidemiology ;— Timing of sexual intercourse in relation to ovulation: Effects on the probability of conception, survival of the pregnancy, and sex of the baby.

N Engl J Med ; 23 — Fact sheet on the safety of levonorgestrel-alone emergency contraceptive pills. Geneva: WHO, Assessment report: EllaOne. London: EMA, Bringing emergency contraception over the counter. Contraception ;68 2 — Advance provision of emergency contraception for pregnancy prevention full review.

Guidelines for preventive activities in general practice. Search PubMed. Back to search results. Also in this issue: Skin May Focus Optimising cryosurgery technique.

Scabies: A clinical update. They can sometimes cause heavy or painful periods, tummy swelling and urinary problems. Surgery is the most common treatment for fibroids which cause symptoms. Ulipristal acetate is prescribed to reduce the size of the fibroids before the surgery. The female hormone progesterone is thought to play a role in the development of fibroids. Ulipristal acetate works by blocking the effects of progesterone. This stops the fibroids from growing and they shrink in size.

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken.

For these reasons, before you start taking ulipristal acetate for uterine fibroids it is important that your doctor knows:. Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with ulipristal acetate. You will find a full list in the manufacturer's information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine but speak with your doctor or pharmacist if any of the following continue or become troublesome.

If you experience any other symptoms which you think may be due to the tablets, please speak with your doctor or pharmacist for further advice. Never take more than the prescribed dose. If you suspect that you or someone else might have taken an overdose of this medicine, go to the accident and emergency department of your local hospital.

A temporal comparison between the aforementioned EC methods is shown in Table 1. P4 exerts its action on the normal reproductive functions of women through its interaction with two isoforms of intracellular receptors with transcriptional activity, PR-A and PR-B Mote et al. UPA binds with high affinity to both isoforms of PR, exhibiting agonist and antagonist properties Blithe et al. This drug is distributed bound to plasma proteins, such as albumin, whereas neither sex hormone-binding globulin SHBG nor corticosteroid-binding globulin CBG appears to serve as serum carriers for UPA in monkeys or humans Larner et al.

Its metabolization would be mainly through cytochrome P and its mono-demethylated metabolite is pharmacologically active Snow et al.

During the past years, efforts have been made to elucidate the mechanisms underlying UPA activity as EC with the idea that a better understanding of its mode of action is crucial to give women the possibility to choose in an informed manner among the different available methods.

The present review summarizes the available data on the mechanisms through which UPA may act when used for preventing pregnancy after unprotected sexual intercourse. Another study that specifically evaluated its effectiveness between 48 and h after intercourse showed that the pregnancy rate after UPA intake was only 2. Moreover, when the pill intake took place between 96 and h, only 1. A large body of evidence has shown that UPA has an inhibitory effect on ovulation when administered during the follicular phase.

In particular, during the mid-follicular phase, with follicles between 14 and 16 mm in diameter, a single dose between 10 and mg produced a delay in follicular rupture and suppression of plasma levels of estradiol Stratton et al. However, once LH levels had reached maximum values at the time of UPA administration, women ovulated normally.

Moreover, a pharmacodynamic study based on repeated use of UPA every 7 or 5-day pill-intake during 8 weeks showed that the drug delays follicular rupture but ovulation eventually occurs with time in most subjects Jesam et al. It should be noted that the murine model has become a tool to investigate the molecular mechanisms by which UPA could block the follicular rupture. In this regard, later studies in this animal model demonstrated that the observed anti-ovulatory effect was the consequence of a repression of PR-regulated genes critical for ovulation Nallasamy et al.

When the drug was administered 8 h after hCG or later, UPA effectiveness to inhibit ovulation significantly declined Nallasamy et al. As previously shown, unlike LNG whose anti-ovulatory effects are restricted to the follicular phase prior to the increase in LH levels, UPA inhibits follicular rupture even if it is administered during the LH surge Brache et al. However, given that the LH peak may occur within the h window women have to take the UPA pill, the anti-ovulatory effect would not seem to be sufficient to justify the high effectiveness described for UPA.

In this regard, a Hong Kong-based clinical trial including women who required EC showed that administration of a 30 mg UPA pill is able to prevent pregnancy even after ovulation has occurred percentage of pregnancies prevented calculated for included patients: post-ovulation: Although statistical significance was not reached, the authors attribute it to the modest sample size analyzed in their study Li et al.

These clinical results emphasize the idea that although today UPA is the most effective oral option as EC, more studies are still required to fully clarify its mechanism of action. In their transit through the female reproductive tract, spermatozoa are exposed to increasing levels of P4 secreted by the cumulus cells and the corpus luteum.

Considering that sperm are transcriptionally inactive cells, these effects would be mediated by non-genomic P4 membrane receptors.

Although the identity of the protein or protein complex that leads to the occurrence of P4-induced phenomena in sperm has not been elucidated so far, UPA could exert agonist or antagonist action on them, affecting sperm function.

In this regard, spermatozoa may be stored up to 5 days within the female genital tract before fertilization, the reason why fertile days of the menstrual cycle are the 5 days preceding ovulation and the day after LH peak Wilcox et al. This period of time would be an opportunity for UPA to interfere with sperm function regardless of the timing of the pill intake and the LH peak in the pill-user.

Initial studies in rats evaluated the effect of UPA on the male reproductive tract Wang et al. No effect on epididymal maturation, post-meiotic sperm development, spermatogenesis, and fertility were observed. Nonetheless, UPA prevented DNA damage of human spermatozoa in vitro , probably due to a detoxification activity of the drug of the reactive oxygen species ROS produced by sperm metabolism in culture Munuce et al. In addition, in the presence of a P4 gradient, UPA induced a chemo-repellent behavior in sperm Guidobaldi et al.

Although this direct effect was observed at lower concentrations than those in pill-users sera, these results opened the possibility that sperm fertilizing ability could be compromised in the presence of UPA.

Therefore, gamete interaction was a possible target for UPA actions on events occurring after ovulation and before implantation. Considering the ethical reasons involved in the use of human oocytes for gamete interaction research, an experimental approach through heterologous gametes assays as mouse cumulus penetration and hamster oocyte penetration test HOPT allowed the indirect evaluation of UPA effects on human sperm-fertilizing ability.

At concentrations comparable to those found in pill-users serum, UPA did not impair the human sperm ability to either penetrate the cumulus or to fuse to and penetrate the egg, supporting the idea that the drug does not interfere with, at least, these stages of the sperm—egg interaction process Zumoffen et al. The use of the mouse model allowed the evaluation of the effect of UPA on the complete homologous in vitro fertilization IVF process as well as in early embryo development Gomez-Elias et al.

When cumulus—egg complexes were used, the presence of the drug did not affect IVF, suggesting that hyperactivation and acrosome reaction, the two critical P4-dependent processes required for fertilization, occurred normally in UPA-incubated mouse spermatozoa. IVF was also performed with cumulus-free mouse eggs, a condition that not only evidences subtle deficiencies in sperm-fertilizing ability Nishimura et al. In this case, the presence of UPA did not alter the fertilization rate, supporting that the drug does not interfere with sperm-egg interaction Gomez-Elias et al.

In vitro and in vivo experiments in mouse showed the lack of effect of UPA on embryo early development, measured not only by the percentage of blastocysts obtained in the presence of the drug but also by the kinetics of in vitro development to the blastocyst stage Gomez-Elias et al. These results are similar to those obtained with LNG Munuce et al. Most of these actions are mediated by muscular contractions and ciliary activity in the oviduct Lyons et al.

In accordance with this, the expression of PR in ciliated epithelial cells of adult mice and human oviducts has been demonstrated Teilmann et al. Different studies have reported that the pharmacologically relevant dose of UPA inhibits both ciliary beat and muscle contraction of fallopian tube strips in vitro Li et al.

Sperm can be retrieved from the fallopian tubes within 5 min to 2 h after insemination in the vagina Kunz et al. Therefore, the effect of UPA on the oviduct could alter sperm interaction with the oviductal epithelium. However, the lack of effect of UPA on the ability of human spermatozoa to interact in vitro with human tubal explants Zumoffen et al.

Therefore, impairment of sperm-oviduct interaction and the subsequent sperm distribution would not be a mechanism of UPA-mediated EC. As stated before, evidence does not support a significant direct effect of UPA on human sperm function nor on sperm-oviductal epithelium interaction. However, these results did not evaluate the possible effect of UPA on in vivo sperm transport through the female genital tract, a parameter that is not feasible or ethical to analyze in humans.

It is important to point out that UPA would not alter the cervical mucus viscosity precluding a possible effect on sperm transit to the uterine cavity Jesam et al. The development of a mouse model in which UPA was administered just after mating and when ovulation has already occurred showed no effect of the drug on the percentage of fertilized eggs Gomez-Elias et al.

In addition, the finding that injection of UPA just before mating did not affect in vivo fertilization Gomez-Elias et al. Transport of the embryo through the oviduct to the site of implantation in the uterus could also be modulated by oviductal mobility and, therefore, it could constitute another possible point of action of UPA. As a consequence, an alteration in embryo transport could result in a desynchronization between the resulting blastocyst and the endometrium for its correct implantation.

Although the effect of UPA on human embryo transport has not been studied because of ethical and technical limitations, the results obtained when using animal models have shed light on this possibility. This could also be the case in humans considering the fact that the risk of ectopic pregnancies in UPA users did not differ from that observed in the general population Levy et al. In summary, although the in vitro inhibitory effects of UPA on ciliary beating and muscle contraction of the fallopian tubes have been described, studies performed so far indicate that, if any in vivo effects exist, they would not have a strong impact on the transport or interaction of gametes and embryos.

P4 plays a fundamental role in implantation by acting on the acquisition of endometrial receptivity, embryo adhesion and decidualization Ramathal et al.

In the proliferative phase, both isoforms are present in both compartments, although PR-A is found in greater proportion. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv aafp. Want to use this article elsewhere? Get Permissions. Read the Issue. Sign Up Now. Previous: Rapid-Onset Skin Rash.

Aug 15, Issue. Bottom Line Ulipristal is a prescription-only emergency contraceptive. Read the full article. Get immediate access, anytime, anywhere. Choose a single article, issue, or full-access subscription. Earn up to 6 CME credits per issue. Purchase Access: See My Options close. Best Value!