"We must reassess the benefit / risk of the Lutéran and Lutényl pills"

Illustration of contraceptive pills.

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• After Androcur, other progestogen pills (Lutéran and Lutényl) are the subject of an alert from the ANSM, because they increase the risk of brain tumor.

• A limited risk which should not make patients panic, but invite them to reassess the benefit / risk balance with their doctor.

  The ANSM gives them the floor via a call for contributions.

• To better understand the situation,

  20 Minutes

  interviewed Isabelle Yoldjian, head of the gynecology department at ANSM.

Which contraceptive pill to take?

The choice is limited as alerts from the National Medicines Safety Agency (ANSM) multiply.

After the scandal around Diane 35, the new recommendations on Androcur, it is now two progestin-only pills, Lutéran and Lutényl, which are in the sights of the ANSM.

In June 2020, she published a warning about these two treatments and their generics, which increase the risk of meningioma, a benign brain tumor in most cases.

An alert based on an epidemiological study carried out on more than 3 million patients by Epi-Phar.

In this new school year, the agency is launching a call for contributions until September 30 so that all women who undergo these treatments can share their experience and their concerns.

To better understand this alert and the interest of this consultation,

interviewed Isabelle Yoldjian, head of the gynecology department at ANSM.

What are the risks for women who are on Lutéran or Lutényl and their generics?

The investigation into Androcur revealed an increased risk of meningioma, so it was logical to focus on the little brothers, two other macro-progestins.

A large epidemiological study revealed at the beginning of June an increased risk of developing a meningioma for a woman treated with Lutéran and Lutényl.

With a dose effect: the longer the treatment is taken at a high dose, the greater the risk.

Clearly, a woman who takes these treatments for more than six months is approximately 3.3 times more likely to develop this disease than a woman who does not.

From the age of five, the risk is multiplied by 12.5 for Lutényl, and by 7 for 3.5 years under Lutéran.

Something to panic about… What to say to the many women who have been taking this treatment for years?

Developing a meningioma, a benign brain tumor, is not systematic.

But it is important to be aware of this risk in order to limit it.

Women who have taken the treatment for many years should check that they do not have neurological symptoms.

If this is the case, or if they are over 35 and have been taking these drugs for more than five years, healthcare professionals should suggest that they perform brain imaging.

A priori, there is no risk of stopping this treatment.

On the other hand, if a woman finds herself relieved in case of endometriosis, she may decide to continue it after discussion with her doctor.

This is why each patient is invited to reassess the benefit / risk with her doctor.

The ANSM has launched a call for contributions.

For what purpose, when you had already published recommendations?

The results of the epidemiological study were known in early July.

It was important to put in place immediate measures to limit this risk.

But we did not look at the therapeutic indications.

These calls for contributions will enrich the public consultation, which will take place on November 2.

To discuss with women, patient associations and health professionals to find out what the indications for which Lutéran and Lutényl remain appropriate in view of the risk of meningioma.

Before taking any measures, we had to make sure that all aspects were covered and that we were going to take all the issues into account.

Last week, we had received around 40 contributions.

It's a lot.

For the only other call for contributions launched by the ANSM, we had a hundred in all.

What will the next steps be?

At the end of this public consultation, the ANSM will publish specific recommendations for women and doctors in order to know how to properly use these treatments.

These drugs have very varied indications: contraception, menstrual pain, endometriosis, breast pain, disorders preceding menstruation, fibroma, pre-menopause ... Perhaps some are no longer justified.

More broadly, the ANSM continues to monitor progestin-only pills.

Because there are others, as well as progestin-based IUDs.

From the moment we are interested in a product, we investigate the whole family ...

Precisely, you had launched the same approach for the Androcur.

With what consequences?

For Androcur, we achieved what we wanted.

We knew that there was an increased risk of meningioma since it had been written in the instructions for ten years.

What was not known was the quantification of the excess risk: after X years, the risk is multiplied by Y. And at what dose.

We discovered that after six months, the risk was multiplied by 7. We obtained a considerable drop in the use of Androcur, since we went from 90,000 patients treated before the ANSM communications in September 2018 to 11,000 in 2020. That is to say a reduction in prescription of around 80%.

Before the alert, France represented 60% of the consumption of Androcur in Europe!

Androcur, Lutéran and Lutényl are progestins.

Why not have alerted directly to these three treatments?

Have we not wasted time?

We couldn't do everything at the same time, it was way too big.

Between 500,000 and 600,000 women take Lutéran or Lutényl or their generics.

Moreover, the problem is not as much a non-Marketing Authorization (AMM) problem as Androcur.

For the latter, there was overuse for moderate acne or hirsutism, whereas it is normally prescribed in severe hirsutism related to polycystic ovary syndrome.

From contraception to menopause, a woman will easily use Lutényl or Lutéran one day or another.

Finally, there was no pharmacovigilance signal on Lutéran and Lutényl before February 2019. A 2016 study revealed less than ten cases of pharmacovigilance.

All the communication around Androcur has certainly freed the word on the other pills.

Lutéran has not been sold since September in France… Is this alert still useful?

Yes, because Lutéran does not occupy the priority market share.

Lutenyl, and especially the generics of these two drugs, are used much more.

This is why we mention in our press releases the molecules, nomegestrol acetate (Lutenyl and generics) and chlormadinone acetate (Lutéran).

These three treatments are believed to provide relief for women with endometriosis.

What alternatives will they have?

These two molecules are not part of the recommendations of the High Authority of Health in case of endometriosis.

We know that these treatments are used, but there is no clinical trial that proves their effectiveness.

The first-line medical treatment is a continuous 2nd generation pill to avoid having your period.

Or the Mirena IUD.

More and more alerts concern contraceptives.

Is access to contraception hampered?

It is a subject.

There is concern among healthcare professionals about the discrediting of hormones in general, not just during contraception.

These comprehensive discussions with patients should be kept in mind that this kind of alert may lead to a delay in pills that can cause venous thromboembolic disorders.

Society

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Health

For the ANSM, certain progestin drugs increase the risk of brain tumors

• Endometriosis

• Interview

• Women's health

• Society

• Contraceptive pill

• Health