Danazol
by Ros Wood
Danazol has been used to treat women with endometriosis since the 1970s [1]. It was the most commonly used drug in the early 1980s, but its use declined markedly after the introduction of the GnRH agonists in the late 1980s and early 1990s.
Danazol is a synthetic androgen [1]. Androgens are hormones produced by the male testes. They are responsible for the functioning of the male reproductive system and the development of the male characteristics, such as facial hair and a deep voice. The ovaries also produce small amounts of androgens.
Danazol is an effective treatment for endometriosis, and has the same effectiveness as the other hormonal treatments. However, it has many androgenic (male-like) side effects, including weight gain, increased body hair and acne. Its unpleasant side effects and its tendency to adversely affect blood lipid (cholesterol) levels mean it is not usually the first choice of treatment for endometriosis [1].
How it works
Like all the other hormonal treatments, danazol does not cure endometriosis permanently. Rather, it suppresses its growth and development temporarily, so the disease may recur following treatment.
Danazol has a multitude of effects on the body. Some of these effects combine to produce high levels of androgen and low levels of oestrogen in the body. This hormonal environment stops menstruation and suppresses the growth of endometrial implants, causing them to degenerate [1,2].
Most women will stop ovulating and menstruating by the second month of treatment, though this may depend on the dosage used. The symptoms of endometriosis usually begin to diminish by the end of the second month.
Most women will resume ovulating and menstruating within 4–6 weeks of stopping treatment [2].
Dosage
The usual length of treatment is 3–6 months, but it may be extended to 9 months in some circumstances.
The recommended dosages vary. North American gynaecologists tend to recommend dosages of 800 milligrams per day, whereas European and Australian gynaecologists tend to recommend dosages of 600 milligrams per day [3].
Some gynaecologists believe it is better to base the dosage on the minimum needed to stop menstruation. In this case, they may suggest that you start with 400 milligrams per day, and, if necessary, increase the dose until your periods stop [3]. Alternatively, they may suggest that you start with 600 milligrams a day, and reduce the dosage to 400 milligrams a day or even 200 milligrams a day [2].
You should start your course of danazol on the first day of your period to decrease the risk of taking the drug while you are pregnant. If there is any possibility that you may be pregnant, you should have a pregnancy test before starting treatment [4].
Although it is unlikely that you will conceive while on danazol, care should be taken to avoid pregnancy. It is recommended that you use barrier contraception (condom or diaphragm or both) throughout treatment [4].
You should not take danazol if you have [5]:
- liver disease
- high blood pressure
- heart failure
- poor kidney function
| Generic name | Brand name | Form | Dosage |
|---|---|---|---|
| Azol | |||
| Danazol | Cyclomen | Gelatin capsules | 400-800 mg a day |
| Danocrine | |||
| Danol |
Side effects
Danazol can cause many side effects, but there are marked variations in the ways women respond to it. Nevertheless, most women will experience many side effects [2], and many will stop taking it as a result of these [6].
The number and severity of side effects experienced is sometimes related to the dosage being used. Reducing your dosage to the minimum needed to stop your periods may reduce the side effects experienced.
Many of the side effects are due to the fact that it is an androgen[2,4,5]. These include:
- weight gain*
- acne
- oily skin and hair
- change of voice (deepening, husky or petering out at times)
- bloating
- fluid retention
- voice changes
- increase in body hair
- decreased breast size
- decreased libido
- enlargement of the clitoris (rare).
*Weight gain is a common side effect. Most women experience weight gain, usually 1–5 kilograms but occasionally more [2]. When treatment finishes most women lose much of the weight gain within 1–2 months.
Some of the side effects are due to the low levels of oestrogen in the body[4,5]. These include:
- hot flushes
- night sweats
- vaginal dryness
Danazol can also cause other side effects[2,4,5], including:
- irregular vaginal bleeding or spotting
- skin rash
- nausea
- headaches
- muscle cramps
- tingling of the limbs
- emotional instability
- fatigue, adverse effects on blood lipid (cholesterol) levels
- decreased glucose tolerance.
Most of the side effects disappear soon after completing treatment. However, some of the androgenic side effects are sometimes irreversible [4,5], such as:
- deepening of the voice,
- increased body hair (especially if profuse)
- enlargement of the clitoris.
If you develop any of these side effects, notify your gynaecologist immediately.
Long-term use is associated with a small risk of developing liver tumours and a theoretical risk of developing heart disease [2]. If your treatment is lasts longer than 6 months, your liver function should be monitored [2].
» Tips for coping with the side effects of drug treatments
Effectiveness for pain symptoms
Clinical trials have shown that danazol is as effective as the other hormonal treatments in relieving the pain symptoms of endometriosis [5,6]. It relieves pain in approximately 90% of women [7]. However, it does not always relieve symptoms completely [6].
Symptoms often recur following hormonal treatment [5]. The recurrence of symptoms may occur months or years after treatment ceases. One unpublished study found that 60% of women had had a recurrence of their symptoms within five years of treatment [8].
Use before surgery
There is no evidence to justify using a course of hormonal treatment as a preparation for surgery [5].
Use after surgery
There is some evidence to justify using hormonal treatment following surgery to suppress the growth and development of any remaining or new endometrial implants [5].
Use in recurrent endometriosis
If the drug was effective and well tolerated previously, repeat courses of danazol may be used for women with recurrent endometriosis.
Effectiveness for infertility
Danazol — like all the hormonal treatments for endometriosis — will not improve your chance of conceiving, so it should not be used as a treatment for infertility [9].
Keeping track
You should visit your gynaecologist about six to eight weeks after beginning treatment with danazol to discuss how the treatment is progressing. Contact your gynaecologist if you have any problems between scheduled visits.
Pregnancy and breastfeeding
Danazol should not be used during pregnancy as it can cause masculinisation (development of male-like features) of a female foetus [4]. If you suspect that you may be pregnant while taking danazol, you should stop taking the drug and contact your gynaecologist immediately.
It is not known if danazol is excreted in the breastmilk nor whether it has harmful effects on the infant. Therefore, you should not take danazol while breastfeeding [10].
Interactions
There are no known interactions of danazol with any foods or alcohol. However, it does interact with some medicines, so make sure your gynaecologist is aware of any other medicines you are taking [4].
References
- Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. The Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD000068. DOI: 10.1002/14651858.CD000068.
- Kennedy S. The patient’s essential guide to endometriosis. United Kingdom: Alden, 2003.
- Wingfield M, Healy DL. Endometriosis: Medical therapy. Baillieres Clin Obstet Gynaecol 1993;7:813–38.
- Australian Medicines Handbook Pty Ltd. Australian Medicines Handbook 2004. Australia, Australian Medicines Handbook Pty Ltd, 2004.
- Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E. ESHRE guideline for the diagnosis and management of endometriosis. Human Reprod 2005;20(10):2698-2704.
- Royal College of Obstetricians and Gynaecologists. Clinical green-top guidelines: the investigation and management of endometriosis. RCOG, 2000.
- Biberoglu KO, Behrman SJ. Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness. Am J Obstet Gynecol 1981;139(6):645-54.
- Shaw, R. Moderator’s lecture: Medical therapy. 9th World Endometriosis Congress, Maastricht, 2005.
- Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for endometriosis. The Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD000155.
- Alphapharm Pty Limited. Azol Consumer Medicines Information. Australia, Alphapharm Pty Limited, 2005.
Thank you to the following for reviewing this article prior to its publication:
Stephen Kennedy, Clinical Reader/Honorary Consultant and Head of Department, Oxford University, UK
Mette Haase Moen, Associate Professor and Senior Consultant, Tronheim University Hospital, Norway
