EllaOne: how does the concept of emergency contraception change in young women?

by Martina Maugeri ¹, Francesca Nocera ¹ | January 5, 2021.

1. Pharmacy Student at “Magna Graecia” University of Catanzaro, Italy.

Adolescence is a delicate psycho-physical training process that involves not only personal behaviour but also relationship with other people. Adolescents may be more affected by social pressure regarding intimate choices like sexual intercourse, without having full knowledge of what the emotional, physical and psychological consequences will be. A statistical study carried out by the Eurispes Institute has found a decrease in the age at which young people begin sexual activity, which in Italy is on average around 15 years old. It is, therefore, necessary to provide correct and comprehensive information on various aspects of sexual education, such as what are and how to do preventive and emergency contraceptive methods work. 

• Preventive contraceptives are the methods used to prevent pregnancy, such as barrier methods to be used during intercourse (i.e. condoms) and hormonal methods to be used before intercourse (i.e. the estroprogestinic pill, contraceptive ring, transdermal patch).

• Emergency contraceptives include medications to be taken following unprotected intercourse that occurred during the woman’s fertile period, from 4 to 5 days preceding up to 1 day following ovulation.

What is ovulation?

Ovulation is a phase of the female ovarian cycle that occurs around day 14, culminating in the rupture of the follicle and the release of the mature ovum from the fallopian tube into the uterus to be fertilized by the sperm. It represents the most fertile phase for women. When the follicle is mature estrogen levels start to increase, followed by a peak of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels that mark the beginning of the ovulation. After ovulation, in the luteinizing phase, LH causes the transformation of the rest of the follicle into corpus luteum, which secretes less and less estrogen and begins to produce progesterone, whose concentration increases progressively. Progesterone is a female steroid hormone, which stimulates the endometrium (mucous membrane covering the inner cavity of the uterus) to thicken and produce the substances necessary for the implantation of the eventual fertilized ovum (Figure 1). If no conception occurs, the uterine lining, as well as blood, will be shed during menstruation.

Ovulation and emergency contraception

The activity of progesterone can be modulated by certain drugs in order to create alterations in the hormonal cycle and inhibit the process of fertilization of the ovum, as is the case with emergency contraception.

Commonly available methods are:

• Oral progestin preparations containing levonorgestrel, sold in packages containing one 1.5 mg tablet to be taken in a single administration within 72 hours of unprotected sexual intercourse;

• Oral preparations containing ulipristal acetate, which contains 1 30-mg tablet to be taken in a single administration within 120 hours of unprotected sexual intercourse (Figure 2).

Ulipristal acetate (sold under the brand name EllaOne®) is derived from 19-norprogesterone, and is an orally active, synthetic selective progesterone receptor modulator that acts by binding with high affinity to the human progesterone receptor. This hormone, whose levels increase throughout pregnancy, has the role of preparing the uterus to receive and protect the embryo, so when ulipristal acetate is taken for emergency contraception, the physiological function of progesterone receptors is altered. This mechanism of action results in the inhibition or delay of ovulation and consequently the suppression of luteinizing hormone (LH) levels rise. Pharmacodynamic data show that, even when taken immediately before the time when ovulation is expected, i.e., at the beginning of the lutein phase, ulipristal acetate is able to reduce the thickness of the endometrium and interfere with implantation of the fertilized ovum. Once taken, ulipristal acetate is rapidly absorbed and it binds to plasma proteins (e.g., albumin), reaching the maximum concentration after approximately one hour. The drug is metabolized in the liver through specific enzymes, forming a biologically active product (11-demethylated), and subsequently eliminated through the faeces (Figure 3).

Posology and side effects of EllaOne

It is an emergency contraceptive that must be taken within 120 hours (5 days) of unprotected intercourse or failure of another method of contraception. The dosage consists of one tablet to be taken orally as soon as possible. If vomiting occurs within 3 hours of taking EllaOne, a second tablet should be taken. The pill can be taken on a full or empty stomach and at any time during the menstrual cycle. It should be noted that this method of contraception CANNOT terminate an ongoing pregnancy. The most commonly encountered side effects are shown in the figure: (in some cases, unusual or irregular vaginal bleeding may occur).

The use of EllaOne is contraindicated in the presence of severe pathological conditions of the kidney and liver as it is mainly metabolized in these two organs. In addition, due to a mild glucocorticoid receptor antagonist effect, it is contraindicated in severe asthma patients and in those women with rare galactose metabolism disorders, since traces of lactose monohydrate are present in the composition. For more information on this matter, we recommend visiting the webpage https://www.ellaone.it/.

How does the sale of EllaOne change?

The marketing authorization of Ulipristal acetate (EllaOne) by the Italian Medicines Agency (AIFA) in 2011 generated widespread debate in Italy. In the following years, many changes regarding the sale regime of the drug made by AIFA, have caused more and more clamour on the media. Finally, last October, with the Determination n. 998/2020, the modification made assumed considerable value from the social point of view and in future perspectives, it anticipates a change in the concept of emergency contraception for women. In fact, the AIFA has established that a prescription will no longer be required for underage women, and EllaOne will pass:

• FROM “Prescription-only medicine to be renewed from time to time” for patients under the age of 18 and “Non-prescription, but not over-the-counter (OTC) medicine” for patients over the age of 18,

• TO “Non-prescription but not over-the-counter (OTC) medication”. (ART. 2 Classification for supply purposes, ASEF/NM Rep. n. 998/2020 Rome, 08-10-2020)

How does this determination impact the pharmacists?

This represents an important change mainly aimed at underage women who, previously “limited” by the obligation of a prescription as well as the legal permit from parents, now have the possibility of going independently to a pharmacy to purchase the emergency contraception drug. However, it is an emergency contraception drug and not something to be used regularly, so it is good to always rely on the advice of the doctor and/or pharmacist, who fulfils the important task of assessing the unique characteristics of each patient. The role of the pharmacist, in fact, will not undergo any big changes, as he remains the figure responsible in front of the customers to inform and pay attention to several aspects, such as interactions with other drugs (such as antiepileptics, anticonvulsants and barbiturates) side effects, storage and administration of the drug, at the time of sale.

The impact of this determination on women: the line between freedom and awareness.

Freedom of choice is a fundamental right, but the responsibility and awareness of being able to decipher the consequences of an option that primarily impacts the woman must not be underestimated. Even more during adolescence, where there is often no full awareness of the consequences that emergency contraception can entail. This is inescapably due to inexperience and young age, which should not take on recriminatory values, but provide more significant incentives for the society to persevere in information campaigns and education on sexuality. It is clear, however, that the choice of AIFA may have two implications: on the one hand, it provides support to young women who, being afraid to turn to parents, doctors, teachers, etc. may choose unconventional or illegal approaches to obtain the drug, on the other there could be an abuse of the concept of freedom that could result in a general superficiality and recklessness in the management of sexual intercourses, due to the increased availability of emergency contraceptives.

In conclusion

The liberalization of emergency contraceptives represents an important result that positively impacts women’s freedom of choice and self-determination in modern society. Despite this, it remains a clear point to be able to instil adolescents to a correct sexual education, encouraging the use of barrier contraceptive methods like condoms. In fact, an aspect of fundamental importance that should not be ignored is that emergency contraception does not protect against sexually transmitted infections (ex. Chlamydia, genital herpes, Papillomavirus, gonorrhoea, HIV, trichomoniasis and syphilis), on the contrary condoms do. In a progressively evolving society, priorities must be oriented to ensure proper education and information for young people, even on issues still considered taboo. Therefore, in matters of sexuality, it is good to share and trust medical sciences rather than media or social networks, because only the former are aimed at protecting the health of people, of all ages.   

References:

1. https://www.aifa.gov.it/-/aifa-abolisce-anche-per-le-minorenni-l-obbligo-di-ricetta-per-la-contraccezione-di-emergenza-fino-a-cinque-giorni-dopo
2. https://www.aifa.gov.it/documents/20142/1134592/2020.10.10_Det-DG-998-2020_modifica_regime_fornitura_ELLAONE_08.10.20.pdf/48c3d0ae-ba87-aadc-e5d8-b281ed0fc467
3. https://www.ema.europa.eu/en/documents/product-information/ellaone-epar-product-information_it.pdf
4. https://www.ellaone.it/foglietto-illustrativo/
5. https://www.empillsblog.com/wp-content/uploads/2014/07/copertina.jpg
6. UPA and LNG in emergency contraception: the information by EMA and the scientific evidences indicate a prevalent anti-implantation effect. Bruno Mozzanega , Giovanni Battista Nardelli. Eur J Contracept Reprod Health Care. 2019 Feb;24(1):4-10. doi: 10.1080/13625187.2018.1555662. Epub 2019 Jan 18.
7. Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens. Vivian Brache et al. Contraception. 2013 Nov.
8. https://www.cblive.it/rubriche/divulgazione-approfondimenti-e-news-su-salute-e-benessere/pillola-dei-cinque-giorni-dopo-decide-il-minore.html
9. http://www.salute.gov.it/portale/donna/dettaglioContenutiDonna.jsp?lingua=italiano&id=956&area=Salute%20donna&menu=societa
10. https://www.ellaone.it/