Endometriosis Hormone Treatment

Hormonal therapy works on the principle that endometriosis is lessened during pregnancy or by menopause. Therefore, the aim of drug therapy is to put patients into a hormonal state of pseudo-pregnancy or pseudo-menopause. Side effects that patients may sometimes experience relate to these conditions.

We use the following hormones:

GnRH Agonists

This is a new class of drugs, which have already been used extensively in most IVF programs. GnRH is the hormone that travels from the brain to the pituitary gland in the brain to release most of the hormones which control ovarian function.

The GnRH agonists are very powerful drugs that mimic this hormone and therefore travel to the brain, but they are up to 2,000 times more powerful than the natural hormone. They therefore cause exhaustion of the pituitary gland in the brain and this means that there is no longer any stimulating factors controlling the ovary.

The ovary goes into a pseudo-menopausal state and refuses to work. This is the basis of treating the endometriosis. Patients on GnRH agonists may have significant menopausal side effects, including hot flushes, dry vagina and mood changes. However these are often well tolerated by patients.
Currently there are three GnRH Agonists available on the Australian market.

The first is Zoladex. This is given as a once a month injection. The drug comes prepared and preloaded in a syringe. A small amount of local anaesthetic is given into the injection site. The hormone is then injected into the layer of fat under the skin. It is then slowly absorbed over the next 28 days. Each injection needs to be repeated very reliably every 28 days. A course of treatment is usually six months.

Lucrin (Leuprorelin) has been used for some time on IVF programs. It is given daily by little subcutaneous injection similar to a diabetic receiving daily insulin. Each bottle contains enough doses for one month and sells for approximately $200.00.

At the moment Lucrin is not available on the pharmaceutical benefits and therefore a six month course of treatment will cost approximately $1,200.00. A further disadvantage is the idea of a daily injection. However the injection is not very painful and can be self-administered. Lucrin is available in the depot form in the United States whereby an injection only needs to be given once a month. It is currently not available in Australia in this form.

The third agonist currently available is Synarel. This is a metered nasal spray which again is used daily or twice daily. The spray is inserted into a nostril and the metered dose given by depressing the spray mechanism and simultaneously sniffing. This gives a reasonably reliable dose of hormone.

It does have the advantage of a very non-invasive form of administration. However absorption can be somewhat variable and some patients with sensitive nasal passages may be irritated by the spray. Also during the 6 month course of treatment if patients get colds or the flu the absorption of the dose may be also be affected.

The current cost of Synarel is approximately $100.00 a month. The cost of a full course of treatment will be approximately $600.00. From October 1994 Synarel has been on the PBS Scheme and costs approximately $20 per month for patients with proven endometriosis.

Progestogenic Agents

Several synthetic progesterone agents are used in the treatment of endometriosis. In general, progestogenic agents are designed to produce a “pseudo-pregnancy” effect, rather than a pseudo-menopause effect.

Progestogenic agents have been used for many years in the treatment of endometriosis, but are probably significantly less effective than Danazol for the same treatment time. The major progestogenic agents used are Duphaston (Dydrogesterone), Provera (Medroxyprogesterone) and Primolut-N (Norethisterone).

Of these, my own preference is for Duphaston, as it is a relatively gentle treatment with fewer side effects. It also has a proven anti-endometriosis effect in good clinical trials.

The side effects of progestogenic agents include weight gain, loss of libido, depression, breast changes, irregular vaginal bleeding and significant breakthrough bleeding.

Occasionally, one can also get nausea, ankle and foot swelling, tiredness, acne, increased facial hair and breast tenderness. Primolut-N, in particular, can cause mild masculinising changes of acne and hair growth.

The major problem with Provera and Primolut-N is that they cause significant amounts of breakthrough bleeding, which patients find exceptionally annoying. Sometimes patients can have spotting for as long as three to four months whilst they are on a treatment protocol that involves either Provera or Primolut-N.

In these circumstances, it is better to stop the treatment for a short time or add in some oestrogen therapy to balance the progesterone. Duphaston is used in a dose of one to two tablets twice a day. Provera and Primolut-N can be used either two or three times a day in a manner similar to Danazol.

In general terms, the progestogenic agents are second line rather than front line drugs for the treatment of endometriosis. Whilst the side effects are generally a little less than Danazol, their effect on the endometriosis is also poorer.

Danazol (Danocrine)

This is a very mild anabolic steroid which is an effective treatment for endometriosis. Patients generally go on Danazol for four to eight months (average of six months). This drug works on the “pseudo-menopause” theory and, as such, the patients will usually lose their periods for the time they are on Danazol.

Output of ovarian hormones is suppressed, so the stimuli which encourage endometriosis to grow and expand are removed. It is also possible that Danazol has an effect directly on the endometriosis. Endometriosis, in the majority of patients, will respond well to Danazol. In fact, quite spectacular cures have been achieved despite quite severe levels of endometriosis.

The side effects of Danazol relate to the fact it is a mild, male type hormone which induces pseudo-menopause. Most patients gain some weight, usually about 3 to 4 kilograms. This always engenders some panic initially, but this weight gain is reversible. It can also be prevented by careful dieting and it is often muscle rather than fat which causes the weight gain.

Other “male” type side effects are mild acne, an increase in body hair, tender muscles, a noticeable increase in strength (particularly if you workout in a gym) and, very rarely, voice deepening. All of these previous side effects occur in fewer than 10% of patients. The only significant and irreversible one is the voice deepening, which hardly ever occurs but if any mild changes in voice are noted then the drug should be ceased immediately.

Side effects of Danazol which relate to the pseudo-menopause effect include a dry vagina; a decrease in libido; hot flushes which begin soon after starting Danazol and usually resolve within several weeks; mood changes and irritability; and a decrease in breast tissue.

Very rarely, a patient can be genuinely allergic to Danazol and develop a skin rash. Danazol should not be taken in pregnancy as it could masculinise a female foetus. Danazol is generally tolerated by patients and it is rare to have to cease the drug or change to another form of therapy.

Many side effects will resolve as the patient becomes more used to Danazol. Side effects can also be dose-related, so we tend to start patients on lower to medium level doses of Danazol, such as 2 to 3 tablets per day, rather than the higher doses of 4 to 5 tablets per day.

Danazol is now rarely prescribed as the GnRH Agonists are equally effective and have fewer side effects.

Gestrinone

Gestrinone is a drug which has been tested in Australia recently and has now been released for general use. It works by the pseudo-menopause effect and has side effects similar to Danazol in terms of causing hot flushes and a dry vagina. It may have the advantage of being able to be used on a two or three times a week dosage.

Early trials using Gestrinone suggest it is as effective as Danazol for treating endometriosis but may not necessarily be more effective than Danazol for treating endometriosis. It could have fewer masculinising type side effects than Danazol.