Megestrol (also called Megestrol acetate) is a prescription hormonal medicine and a man-made version of the hormone progesterone. It belongs to the group of medicines called progestins. Doctors use it in two main ways. It helps improve appetite and reduce weight loss in people who are seriously unwell, such as people with AIDS or advanced cancer. It is also used in advanced breast cancer and advanced cancer of the lining of the womb (endometrium), where the aim is to relieve symptoms and improve comfort. It comes as tablets and as two strengths of liquid. It does not replace surgery, radiotherapy or chemotherapy, and it is not meant for preventing weight loss in people who have not started losing weight.

Megestrol has one active ingredient. It comes as tablets of 20 mg and 40 mg, as a liquid holding 40 mg in each millilitre, and as a stronger, concentrated liquid holding 125 mg in each millilitre. The two liquids contain different amounts of medicine in the same volume and cannot be swapped for one another.

Doctors prescribe it for two different problems. The first is loss of appetite, poor nutrition and serious weight loss in people with AIDS, which is what the liquid forms are approved for. The second is advanced cancer of the breast or of the lining of the womb, where the tablets are used as palliative treatment. Palliative means the aim is to relieve symptoms and improve comfort, not to replace surgery, radiotherapy or chemotherapy.

Reviews of the research show a modest benefit. A 2018 review pooled nine studies in 575 people and found that those taking Megestrol gained an average of 2.25 kg more than those taking a placebo. An earlier Cochrane review reached a similar conclusion and reported better appetite with Megestrol than with placebo. The 2018 review found more side effects with Megestrol than with placebo, and the earlier Cochrane review found that swelling and blood clots were more frequent with Megestrol than with placebo. The 2018 review also found no clear improvement in quality of life. Both concluded that there is not enough evidence to say which dose works best. The prescribing information itself says the precise way the medicine improves appetite and weight is unknown.

Because of these risks, Megestrol is used under medical supervision. Long-term use has been linked to the body's own cortisol system being suppressed (adrenal insufficiency), to Cushing's syndrome, and to new or worsening diabetes. Blood clots, including clots in the legs and in the lungs, have been reported and can be fatal. The medicine may harm an unborn baby, so it is not used in pregnancy. Your doctor will want to know about any history of blood clots, diabetes, heart failure, or kidney or liver disease before you start, and will review your treatment while you take it.

• Loss of appetite and serious weight loss in AIDS - the liquid forms are approved for treating anorexia, cachexia (severe weight loss with muscle wasting) or an unexplained, significant weight loss in people with AIDS. Treatment should start only after other treatable causes have been looked for and dealt with.
• Advanced breast cancer (palliative care) - the tablets are approved for palliative treatment of advanced breast cancer that has come back, cannot be operated on, or has spread to other parts of the body.
• Advanced cancer of the lining of the womb (endometrium) - the tablets are approved for palliative treatment of advanced endometrial cancer in the same situations.
• Poor nutrition in other serious illnesses - MedlinePlus notes that Megestrol is also used to treat malnutrition in people with cancer.
• Not for preventing weight loss - the prescribing information says it is not intended to prevent weight loss in people who have not yet developed it.

1. Helps bring back appetite - reviews of the studies found that people taking Megestrol reported a better appetite than people taking a placebo.
2. Produces a modest weight gain - in a review of nine studies in 575 people, those taking Megestrol gained an average of 2.25 kg more than those taking a placebo.
3. Approved for two different problems - it is used for appetite and weight loss in AIDS, and as palliative treatment in advanced breast cancer or advanced cancer of the lining of the womb.
4. Liquid forms in two strengths - the liquids come in a regular strength and a concentrated strength, including a small once-daily volume for the concentrated one.
5. Started only after other causes are dealt with - the prescribing information says treatment should begin only after other reasons for weight loss, such as infections or unsuspected tumours, have been looked for and treated.
6. Long use in palliative care - it was approved for anorexia and weight loss in AIDS in 1993, and it has been used in palliative care since then.

Weight gain is expected with Megestrol, because that is part of what the medicine is being used for. The other side effects listed below come from studies in people taking it.

Common Side Effects (Usually Mild and may lessen with continued use)

The events listed here were the ones reported most often in the studies.

• Diarrhoea, which was the most common side effect reported in the studies, affecting up to about 15 in 100 people
• Feeling sick (nausea) or being sick (vomiting)
• Wind (flatulence) and indigestion
• Rash
• Headache
• Feeling weak or very tired (asthenia)
• High blood pressure (hypertension)
• Trouble falling asleep or staying asleep (insomnia)
• Fever
• Low red blood cells (anaemia)
• Loss of interest in sex, or trouble getting or keeping an erection
• Unexpected vaginal bleeding or spotting between periods, called breakthrough bleeding. In the studies of the liquid, all 10 women who took part reported this. Tell your doctor.
• Raised blood sugar (hyperglycaemia)

The events listed here are reported less often, in about 1 to 3 in 100 people, or are named in the prescribing information without a stated frequency.

• Swelling of the ankles, feet or legs (oedema)
• Hair thinning (alopecia)
• Hot flushes, sweating, and changes in mood
• Numbness or tingling in the hands, which can be a sign of carpal tunnel syndrome, where a nerve in the wrist gets squeezed

Serious Side Effects (Seek Urgent Medical Attention)

• Blood clots (thromboembolism): pain, swelling, warmth or redness in a leg, sudden shortness of breath, chest pain, or coughing up blood. Clots in the veins, including clots that travel to the lungs, have been reported with Megestrol and can be fatal.
• Adrenal insufficiency: long-term use can hold down the body's own cortisol system, and this can also happen when the medicine is withdrawn after long use. Signs include low blood pressure, dizziness, weakness, feeling sick and vomiting. The prescribing information warns that if this is not recognised it can be fatal, and that steroid replacement treatment may be needed.
• Cushing's syndrome: long-term use has been reported to cause Cushing's syndrome, which means the body is carrying the effects of too much cortisol, the hormone that helps control stress and blood sugar. Signs include weight gain around the middle and the face, a rounded face, easy bruising and purple stretch marks.
• New or worsening diabetes: extreme thirst, passing urine much more often than usual, extreme hunger, blurred vision or confusion.
• Heart failure or fluid overload: rapid weight gain, swelling that gets worse, or breathlessness when lying flat.
• Tumour flare: a temporary worsening of cancer-related pain or symptoms when treatment starts, sometimes with a raised level of calcium in the blood. Tell your doctor.
• Signs of a stroke: sudden weakness or numbness of an arm or leg, a face that drops on one side, or slow or difficult speech.

• Take Megestrol exactly as your doctor has prescribed. Do not take more or less of it, or take it more often, than prescribed.
• Swallow tablets whole with a drink of water. Only split a tablet if your doctor or pharmacist has told you that yours can be split.
• Shake the liquid well before each use to mix the medicine evenly. Measure the dose with the cup or syringe that came with the bottle, not with a kitchen spoon.
• Take it at around the same time or times each day. Tablets and the 40 mg/mL liquid are usually taken in divided doses through the day, while the concentrated 125 mg/mL liquid is usually taken once a day.
• Never switch between the regular liquid and the concentrated liquid on your own. They contain different amounts of medicine in the same volume.
• Keep to the same daily routine with food. If you take your dose with breakfast, keep doing that rather than changing from day to day.
• Keep taking it for as long as your doctor advises. Do not stop suddenly on your own, because the body's cortisol system may need to recover gradually after long use.

Megestrol is a progestin, which means it is a man-made version of progesterone, the hormone that prepares the lining of the womb each month and helps control the monthly cycle.

The prescribing information says the precise way Megestrol improves appetite and weight in people who are seriously ill is unknown. What is known comes mainly from studies in cancer. In cancer of the lining of the womb, the prescribing information describes two possible ways it acts: it lowers the signals from the pituitary gland (a small gland at the base of the brain) that tell the body to make oestrogen, and it may also act directly on the cancer cells in the womb lining. In breast cancer, it changes the way other hormones act on breast tissue and may have a direct effect on the cancer cells themselves.

The medicine also has some cortisol-like (glucocorticoid) activity. The prescribing information warns that this activity has not been fully studied, and it explains why long-term use has been linked to Cushing's syndrome and to raised blood sugar.

Megestrol is absorbed from the gut slowly and variably. In a study of 23 healthy men taking 160 mg a day, blood levels of the medicine peaked about 2 hours after each dose, and the average time the body took to clear half of a dose was about 34 hours, with a range from 13 to 105 hours. Most of the medicine leaves the body in urine: in studies where a small amount of the medicine was tagged so it could be followed, a mean of 66.4% was found in urine within 10 days and a mean of 19.8% in faeces. Only 5% to 8% of a dose leaves the body as breakdown products.

• Take your dose at the same time or times each day, and set a phone alarm if that helps you remember.
• Swallow tablets with a plain drink of water. Do not chew or crush them unless your doctor or pharmacist says you may.
• Shake the liquid well each time, and measure the dose with the cup or syringe that came with the bottle.
• Never swap the regular liquid for the concentrated liquid on your own. The two strengths are not the same.
• If you have been given the concentrated liquid, remember that it is a small once-daily dose.
• Keep eating and drinking normally unless your doctor advises otherwise.
• Weigh yourself about once a week and write the figure down, so you can tell your doctor if your weight changes quickly.
• Report new leg pain, swelling of a leg, or breathlessness without waiting for your next appointment. Blood clots need urgent attention.
• Keep a list of everything you take, including medicines you buy without a prescription.
• Do not stop the medicine suddenly. If you and your doctor decide to stop after long use, ask how to do it safely.

• Tablets: store at 25°C (77°F). Short trips between 15°C and 30°C (59°F to 86°F) are allowed. Keep them below 40°C (104°F).
• The 40 mg/mL liquid: store between 20°C and 25°C (68°F to 77°F), tightly closed and protected from heat.
• The concentrated 125 mg/mL liquid: store between 15°C and 25°C (59°F to 77°F), tightly closed and protected from heat.
• Storage instructions differ between the strengths, so follow the label on your own pack.
• Keep the medicine in the container it came in, out of the sight and reach of children and pets, and away from damp places such as the bathroom.
• Do not flush unwanted medicine down the toilet. Ask your pharmacist about a medicine take-back scheme or the safe way to dispose of it locally.

• Normal diet: keep eating as usual unless your doctor advises changes. No food or drink is listed as something to avoid with Megestrol.
• Food and the liquid: the effect of food on how much of the liquid gets into the body has not been tested, so take your dose the same way each day rather than changing between taking it with food and taking it on an empty stomach.
• Alcohol in the liquid: the 40 mg/mL liquid contains ethyl alcohol as an inactive ingredient, and the label does not say how much. The tablets do not contain alcohol.
• Lactose in the tablets: some tablets contain lactose, which matters if you cannot tolerate lactose.
• Antibiotics: the tablet label notes that blood levels of the medicine can be affected by things that change the gut, including antibiotics. Tell your doctor if you are given antibiotics while taking Megestrol.
• Weight and diet: the label notes that body weight and diet are among the factors that can affect blood levels of the medicine, which is another reason to keep your routine steady.

• Warfarin (a blood thinner): Megestrol may interact with warfarin and raise the INR, the blood test that shows how long blood takes to clot. If you take warfarin, your doctor will check your INR closely.
• Indinavir (an HIV medicine): Megestrol lowers the amount of indinavir in the body. When the two are taken together, a higher dose of indinavir may need to be considered.
• Zidovudine and rifabutin: studies found no significant change in the levels of these medicines, and no dose change is needed.
• Antibiotics: changes in the bacteria in the gut can affect how much Megestrol reaches the blood, so tell your doctor if you start an antibiotic.
• Medicines for diabetes: long-term use can raise blood sugar and worsen diabetes, so your diabetes treatment may need adjusting. Your doctor will check your blood sugar.
• Vitamins, herbal products and supplements: tell your doctor or pharmacist about everything you take, so they can check for interactions.

• A history of blood clots: the prescribing information advises caution in anyone with a history of thromboembolic disease. Tell your doctor if you have had a clot in a leg or lung, or a stroke.
• Diabetes: new diabetes and worsening of existing diabetes have been reported with long-term use. If you have diabetes, your doctor may need to adjust your treatment and will check your blood sugar.
• Serious illness, surgery or infection: long-term Megestrol can hold down the body's cortisol system. During serious illness, surgery or infection the body needs more cortisol, so your doctor may need to give you extra steroid cover. Tell any doctor treating you that you take Megestrol.
• Heart failure: heart failure is listed among the reported side effects, and the medicine can cause fluid retention and swelling. Tell your doctor if you have heart problems.
• Kidney disease: Megestrol leaves the body in urine. Tell your doctor if you have kidney disease.
• Liver disease: the liver helps break the medicine down, and the label notes that liver function can affect the amount reaching the blood. Tell your doctor if you have liver disease.
• Advanced cancer under treatment: the label advises close follow-up for anyone being treated for cancer that has come back or spread.
• Pregnancy: the medicine is not used in pregnancy and may harm an unborn baby.

• Megestrol is a prescription medicine. The amounts below are what the prescribing information describes; your own dose is decided by your doctor.
• Tablets for advanced breast cancer: 160 mg a day, described in the label as 40 mg four times a day.
• Tablets for advanced cancer of the lining of the womb: 40 mg to 320 mg a day, taken in divided doses.
• The 40 mg/mL liquid for appetite and weight loss in AIDS: an initial dose of 800 mg a day, which is 20 mL a day. In studies, 400 mg and 800 mg a day were both found to be clinically effective.
• The concentrated 125 mg/mL liquid: an initial dose of 625 mg a day, which is 5 mL, or one teaspoon, a day.
• The tablets and the regular liquid are taken more than once a day. The concentrated liquid is taken once a day.
• The label says at least two months of continuous treatment is an adequate period for judging whether the medicine is helping.
• Do not change your dose, or stop your medicine, on your own. Follow exactly what your doctor prescribes.

• Taking too much can cause diarrhoea, nausea, stomach pain, shortness of breath, cough, lack of energy, unsteady walking and chest pain.
• If you have taken more than your prescribed dose, contact your doctor or go to the nearest hospital emergency department. Do not wait to see whether symptoms appear.
• Do not drive yourself. Ask someone to take you, or call an ambulance if you feel very unwell.
• Take your medicine pack, the leaflet and any remaining medicine with you so the treating team knows what you have taken.
• Keep any follow-up appointments after an overdose so your doctor can check how you are.

• Take the missed dose as soon as you remember.
• If it is almost time for your next dose, skip the missed dose and take the next one at your usual time.
• Never take two doses at the same time to make up for a missed one.
• If you are not sure what to do, or if you often forget doses, speak to your doctor or pharmacist. A daily alarm or a pill organiser can help.

Get medical help straight away if you have:

• Pain, swelling, warmth or redness in a leg, or pain in the calf
• Sudden shortness of breath, chest pain, or coughing up blood
• Dizziness, fainting or very low energy together with nausea and vomiting, which can be signs of adrenal insufficiency
• Extreme thirst, passing urine much more often than usual, extreme hunger or blurred vision
• Rapid weight gain, worsening swelling of the ankles or legs, or breathlessness when lying flat
• Sudden weakness or numbness of an arm or leg, a face that drops on one side, or slow or difficult speech
• A new or worsening rash, or swelling of the face or lips
• Unexpected vaginal bleeding that is heavy or continues
• Fever, chills or a sore throat that does not settle
• New or worsening pain at the site of your cancer after starting treatment, which can be a tumour flare
• Any chance that you may be pregnant
• Feeling low or confused that does not improve