Treating Endometriosis Hormonally

Endometriosis is a chronic disease. In that sense, there is no cure for endometriosis, but the symptoms can
be reduced with the right treatment. Communication is the key to finding a treatment that fits you.

There are several management options for women with endometriosis, surgical excision of the lesions is the only treatment to remove the disease. In a small percentage of women, endometriosis lesions may recur after excision, the true incidence is unknown.
The best treatment depends on your decisions surrounding fertility and quality of life, it also depends on access to an experienced surgeon.
Many women are offered medical treatments, especially when they are awaiting a diagnosis, surgery or further treatment. These include pain medications, hormonal medications and other drugs used for chronic pain. Medical treatments do not treat endometriosis lesions and can not remove endometriosis. Medical treatments treat symptoms whilst on the treatment, symptoms often recur once the treatment is stopped.

Please discuss your options with your doctor and ask any questions you may have. Your doctor will be happy to explain the different options and answer your questions. Women with endometriosis have either pain, fertility problems or they have both. Treatment of endometriosis focuses on resolving or reducing pain due to endometriosis or on improving fertility, so a patient can get pregnant naturally or through fertility treatments. For treating endometriosis, the doctor can prescribe medical treatment or advise surgical treatment. Both will be explained in detail here and on our Treating Endometriosis (Surgical) page. Depending on the patient, the treatment will be different. Your doctor will take several factors into consideration when prescribing medical treatment or advising surgical treatment. These factors include:

• The preferences of the woman
• The type of disease (peritoneal disease, ovarian cyst or deep endometriosis)
• The severity and type of pain symptoms
• The wish to become pregnant immediately or at a later stage
• The costs and side-effects of some treatments
• The age of the woman
• The treatments she has already received
• The doctor (country, expert centre, experience, skill set)

This means that two women with endometriosis could receive different treatments and even that one woman could receive different treatments over time depending on her preferences, her age, her wish to become pregnant. Important to remember is that medical treatment works only when they are taken as prescribed. Stopping medical treatment often means that the symptoms recur. In the next section, options for medical treatment and surgical treatment will be explained.

Which medication can be used before a definite diagnosis of endometriosis?

When the doctor suspects a woman to have endometriosis related pain, the patient and the doctor can decide that without a definite diagnosis (made by a laparoscopy) the pain is treated as if the patient has endometriosis. This is called empirical treatment or treatment without a definitive diagnosis.

For painful symptoms suspected to be caused by endometriosis, empirical treatment includes analgesia, hormonal contraceptives or progestagens.

Since GnRH analogues have considerable side effects and are very expensive, doctors and patients should consider not using this type of drugs for empirical treatment.

Can I take analgesics (painkillers) for
pain due to endometriosis?

It is important to note that there is little or no evidence for the use of specific analgesics (and other medications for pain) in those living with endometriosis. The evidence is assumed from historical use and studies for other conditions. The lack of trials and strong evidence means that there is no guidance. It may take some trial and error to find a plan that works for you. Your GP and Pain Management Consultant can work with you to achieve a pain management plan.
Analgesics, like paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), are medical therapies that influence how the body experiences pain. These medications are not specific for endometriosis related pain, and they do not have any impact on the endometriosis lesions.

The ESHRE Endometriosis guideline development group recommends that clinicians should consider NSAIDs or other analgesics to reduce endometriosis-associated pain. They are a cost-effective and relatively safe first-line treatment in the management of endometriosis symptoms.

Non-Steroidal Anti Inflammatory drugs (NSAIDs) are a type of pain medicine that can help to relieve the inflammatory pain caused by endometriosis. These drugs work by stopping the release of prostaglandins, one of the main chemicals responsible for pain in general as well as painful menstrual periods. NSAIDs need to be taken one to two days before your period to prevent prostaglandin production and therefore reduce pain. It may take some time, and several doses, for the NSAIDs to block the prostaglandin production and reduce pain. NSAIDs do not shrink or prevent the growth of endometriosis. Examples of NSAIDs in Ireland are Ibuprofen, Ponstan, Naproxen, Difene.
NSAIDs can have some serious side effects that include gastrointestinal bleeding, stomach upset, kidney problems, and high blood pressure. If you are taking an NSAID such as ibuprofen or naproxen, you should take them with or after food, because NSAIDs can irritate the lining of the stomach and sometimes cause bleeding.
Your doctor may prescribe a tablet called a proton pump inhibitor (PPI) to help protect the stomach if they feel you are at risk from an NSAID, or if you need to take them for long periods. Speak to your doctor to be sure they are suitable for you.

Paracetamol (Acetaminophen)
Paracetamol works as a painkiller by blocking the production of prostaglandins, making the body less aware of the pain or injury. Paracetamol reduces temperature by acting on the area of the brain that is responsible for controlling temperature. Paracetamol is a commonly used pain killer, but recent reviews on Cochrane questioned its effectiveness. Paracetamol can be taken with NSAIDs to help manage pain. Paracetamol can have serious side effects if the dose is exceeded. Side effects of paracetamol include a rash, thrombocytopenia (low platelet count) and leukopenia (low number of white blood cells), liver and kidney damage when taken at higher-than-recommended doses. Speak to your doctor to be sure it is suitable for you. Be aware that many over the counter remedies for colds/flu and period pain contain paracetamol.

Paracetamol / Opioid Combined Medications
Co-codamol / Co-dydramol are pain killing drugs is sold over the counter in a low dose with limitations (Solphadine) and is prescribed in higher doses under (Kapake, Solpadol). It is a combination of two drugs – paracetamol and codeine. Doctors often prescribe it to relieve pain after surgery. It is a treatment for moderate pain.
Paracetamol controls pain by blocking prostaglandins. Codeine is a type of opioid. Opioids work by mimicking the body’s natural painkillers, endorphins. They control pain by blocking pain messages to the brain. There are different types of opioids – strong ones and weak ones. Codeine is a weak opioid.
Side effects of Co-codamol include nausea, constipation, drowsiness, sweating, dizziness, dry mouth.

Opioid Medications
Opioid painkillers are prescribed for moderate to severe pain, but physical or psychological dependence and tolerance is a risk if taken regularly.
Therefore, your doctor will not prescribe opioid painkillers to you over long periods of time without regular medical review. Working closely with your GP and pain specialist can help tailor a specific plan for your pain.
Opioids work by binding to certain receptors in your central nervous system, your gut and other parts of your body, and this leads to a decrease in the way pain is felt as well as any reaction to pain.
The most common side-effects of opioids are nausea and vomiting – particularly at the start of treatment – constipation, a dry mouth, drowsiness and confusion.

What are the options for
hormonal treatment of pain?

Hormonal treatments in clinical use are:
– hormonal contraceptives(cyclical use or continuously)
– progestagens (oral or in an Intra Uterine Device)
– anti-progestagens,
– GnRH agonists / antagonists
– aromatase inhibitors

It is important to note that medical (hormonal) treatment in endometriosis is focussed on managing pain and symptoms. Medical treatment should not be prescribed to improve fertility. Choosing a medical treatment can be trial and error, it depends on the type and nature of pain, type and nature of bleeding, the efficacy and side effects of the treatment and the preferences of the patient.

Endometriosis lesions react to the hormonal cycle, the basis of treatment with hormonal treatments is to help suppress the activity of the lesions and thus reduce the pain symptoms.
It is important to know that hormonal treatment does not cure or remove endometriosis. Endometriosis lesions can produce their own hormonal supply; this alongside other factors of endometriosis can lead to a continuation of symptoms. After discontinuation of the treatment symptoms tend to recur. Hormonal treatments are often used when awaiting surgical excision or where surgery is not a preferred option. The ESHRE guideline group does not recommend hormonal treatment before surgery to improve the results of the surgery as there is no evidence to support its use. Following surgery, some patients are offered the oral contraceptive pill or a levonorgestrel-intrauterine system (Mirena). In the immediate term postoperatively the ESHRE guideline group concluded that postoperative hormonal therapy may not improve the outcome of surgery but is an important addition to surgery to prolong the symptom-free interval and prevent recurrence of symptoms. In the longer term, they concluded that the role of postoperative hormonal therapy has no proven benefit (within 6 months after surgery) if this treatment is prescribed with the sole aim of improving the outcome of surgery. Postoperative hormonal therapy could be prescribed for other indications, such as contraception or secondary prevention. In terms of longer-term secondary prevention of recurrence of symptoms, their recommendations are as follows. In a specific population of women with an endometrioma of 3 cm or more, ovarian cystectomy, instead of drainage and electrocoagulation, can be used for the secondary prevention of dysmenorrhea, dyspareunia and non-menstrual pelvic pain. If they do not wish to conceive, women can use regular oral contraceptives for secondary prevention of endometrioma.
In the general population of women operated upon for endometriosis, including ovarian cystectomy for endometrioma, clinicians should advise postoperative use of a levonorgestrel-releasing intrauterine system (Mirena), or combined oral contraceptives for at least 18–24 months, as one of the options for the secondary prevention of endometriosis-associated dysmenorrhea; this does not have proven benefit for the secondary prevention of non-menstrual pelvic pain or dyspareunia. These recommendations are only relevant if the patient is not trying to conceive.

Hormonal treatments in clinical use are:

• Anti-progestagens
• Hormonal contraceptives(cyclical use or continuously)
• GnRH agonists
• Aromatase inhibitors

Medical treatment in endometriosis is focussed on resolving pain. Medical treatment should not be prescribed to improve fertility.

In general, medical treatments can help to reduce pain symptoms in women with endometriosis. Which type of medication fits best to an individual patient depends on the complaints, the efficacy and side effects of the treatment and the preferences of the patient.

Another factor is the cost and availability of a certain treatment. In some countries within Europe, some treatments are not available, they are very expensive, or they are not reimbursed. This information can also influence the decision for a certain treatment

How does hormonal treatment work?

Endometriosis is a problem associated with a woman’s menstrual cycle and dependent on the activity of oestrogens. Endometriosis lesions can also produce their own oestrogen.

The aim of hormonal treatment for pain in women with endometriosis is lowering the estrogen level. It is important to know that hormonal treatment does not cure endometriosis. Hormonal treatment suppresses the activity of the disease and hence the pain symptoms. However, after discontinuation of the treatment symptoms tend to recur. It is not known which patients will have a relapse of pain symptoms.

What are the side effects of
hormonal treatment?

Since the aim of treatment in endometriosis-associated pain is lowering the level of estrogens, the side effects are related to a low estrogen level. Besides that, the side effects are related to the drugs used to reach that low estrogen level.

Side effects are therefore related either to low estrogens (hormonal contraception, GnRH analogues) or to progesterone (hormonal contraception, progestagens).

Some examples of side effects of hormonal treatment for pain in endometriosis are headaches, acne, weight gain, vaginal spotting, fatigue and hot flushes.

These side effects differ strongly between treatments and between patients. As a result, a certain treatment can be a good option for one woman, but the same treatment can have severe side effects in another woman. Your doctor should discuss side effects with you when prescribing hormonal treatment.

Medical treatment before or
after surgery

There is some controversy on this subject. The guideline group does not recommend hormonal treatment before surgery to improve the results of the surgery. Of course, many women in pain get hormonal treatment during a waiting period before surgery. After surgery, starting with an oral contraceptive pill or using a levonorgestrel-intrauterine device may prevent recurrence of pain.

Is surgical treatment an option
for relieving pain symptoms?

Surgical treatment of endometriosis focuses on the elimination of peritoneal endometriosis/endometrioma/deep endometriosis and division of adhesions.

In the past, open surgery or laparotomy was used routinely. Nowadays, laparoscopy is used frequently and preferred since it usually results in less pain, shorter hospital stay, quicker recovery and a smaller scar. However, laparotomy and laparoscopy are equally effective in treating pain symptoms in women with endometriosis.

Therefore, clinicians should consider surgical treatment (elimination of endometriotic lesions) when they see endometriotic lesions during laparoscopy for diagnosis.

If deep endometriosis is suspected, doctors are recommended to refer their patient to a centre of expertise, as these surgeries may be difficult.