Synestrol

Synestrol - General Information

Synestrol is a synthetic, non-steroidal estrogen. It is an estrogen receptor agonist. Estrogens work partly by increasing a normal clear discharge from the vagina and making the vulva and urethra healthy. Using or applying an estrogen relieves or lessens: dryness and soreness in the vagina, itching, redness, or soreness of the vulva. Conditions that are treated with vaginal estrogens include a genital skin condition (vulvar atrophy), inflammation of the vagina (atrophic vaginitis), and inflammation of the urethra (atrophic urethritis).

 

Pharmacology of Synestrol

Synestrol is a synthetic, non-steroidal estrogen. Estrogens passively diffuse into target cells of responsive tissues, complex with the estrogen receptors, and enter the cell's nucleus to initiate or enhance gene transcription of protein synthesis after binding to DNA.

 

Synestrol for patients

ABOUT ESTROGENS

Estrogens are female hormones produced by the ovaries. The ovaries make several different kinds of estrogens. In addition, scientists have been able to make a variety of synthetic estrogens. As far as we know, all these synthetic estrogens have similar properties and therefore much the same usefulness, side effects, and risks. This leaflet is intended to help you understand what estrogens are used for, some of the risks involved in their use, and to help minimize these risks.

This leaflet includes important information about estrogens, but not all the information. If you want to know more, you can ask your doctor or pharmacist to let you read the package insert prepared for the doctor.

USES OF ESTROGEN

THERE IS NO PROPER USE OF ESTROGENS IN A PREGNANT WOMAN.

Estrogens are prescribed by doctors for a number of purposes, including:

1. To provide estrogen during a period of adjustment when a woman's ovaries no longer produce it, in order to prevent certain uncomfortable symptoms of estrogen deficiency. (All women normally decrease the production of estrogens, generally between the ages of 45 and 55; this is called the menopause.)
2. To prevent symptoms of estrogen deficiency when a woman's ovaries have been removed surgically before the natural menopause.
3. To prevent pregnancy. (Estrogens are given along with a progestogen, another female hormone; these combinations are called oral contraceptives or birth control pills. Patient labeling is available to women taking oral contraceptives and they will not be discussed in this leaflet.)
4. To treat certain cancers in women and men.
5. To prevent painful swelling of the breasts after pregnancy in women who choose not to nurse their babies.

ESTROGENS IN THE MENOPAUSE

In the natural course of their lives, all women eventually experience a decrease in estrogen production. This usually occurs between ages 45 and 55 but may occur earlier or later. Sometimes the ovaries may need to be removed by an operation before natural menopause, producing a "surgical menopause."

When the amount of estrogen in the blood begins to decrease, many women may develop typical symptoms: Feelings of warmth in the face, neck, and chest or sudden intense episodes of heat and sweating throughout the body (called "hot flashes" or "hot flushes"). These symptoms are sometimes very uncomfortable. A few women eventually develop changes in the vagina (called "atrophic vaginitis") which cause discomfort, especially during and after intercourse.

Estrogens can be prescribed to treat these symptoms of the menopause. It is estimated that considerably more than half of all women undergoing the menopause have only mild symptoms or no symptoms at all and therefore do not need estrogens. Other women may need estrogens for a few months, while their bodies adjust to lower estrogen levels. Sometimes the need will be for periods longer than six months. In an attempt to avoid over-stimulation of the uterus (womb), estrogens are usually given cyclically during each month of use, that is three weeks of pills followed by one week without pills.

Sometimes women experience nervous symptoms or depression during menopause. There is no evidence that estrogens are effective for such symptoms and they should not be used to treat them, although other treatment may be needed.

You may have heard that taking estrogens for long periods (years) after the menopause will keep your skin soft and supple and keep you feeling young. There is no evidence that this is so, however, and such long-term treatment carries important risks.

ESTROGENS TO PREVENT SWELLING OF THE BREASTS AFTER PREGNANCY

If you do not breast-feed your baby after delivery, your breasts may fill up with milk and become painful and engorged. This usually begins about three to four days after delivery and may last for a few days to up to a week or more. Sometimes the discomfort is severe, but usually it is not and can be controlled by pain-relieving drugs such as aspirin and by binding the breasts up tightly. Estrogens can be used to try to prevent the breasts from filling up. While this treatment is sometimes successful, in many cases the breasts fill up to some degree in spite of treatment. The dose of estrogens needed to prevent pain and swelling of the breasts is much larger than the dose needed to treat symptoms of the menopause and this may increase your chances of developing blood clots in the legs or lungs (see below). Therefore, it is important that you discuss the benefits and the risks of estrogen use with your doctor if you have decided not to breast-feed your baby.

SOME OF THE DANGERS OF ESTROGENS

1. Cancer of the uterus. If estrogens are used in the post-menopausal period for more than a year, there is an increased risk of endometrial cancer (cancer of the uterus). Women taking estrogens have roughly five to ten times as great a chance of getting this cancer as women who take no estrogens. To put this another way, while a postmenopausal woman not taking estrogens has one chance in 1,000 each year of getting cancer of the uterus, a woman taking estrogens has five to ten chances in 1,000 each year. For this reason it is important to take estrogens only when you really need them.

The risk of this cancer is greater the longer estrogens are used and also seems to be greater when larger doses are taken. For this reason it is important to take the lowest dose of estrogen that will control symptoms and to take it only as long as it is needed. If estrogens are needed for longer periods of time, your doctor will want to reevaluate your need for estrogens at least every six months.

Women using estrogens should report any irregular vaginal bleeding to their doctors; such bleeding may be of no importance, but it can be an early warning of cancer of the uterus. If you have undiagnosed vaginal bleeding, you should not use estrogens until a diagnosis is made and you are certain there is no cancer of the uterus.

If you have had your uterus completely removed (total hysterectomy), there is no danger of developing cancer of the uterus.

2. Other possible cancers. Estrogens can cause development of other tumors in animals, such as tumors of the breast, cervix, vagina, or liver, when given for a long time. At present there is no good evidence that women using estrogen in the menopause have an increased risk of such tumors, but there is no way yet to be sure they do not; and one study raises the possibility that use of estrogens in the menopause may increase the risk of breast cancer many years later. This is a further reason to use estrogens only when clearly needed. While you are taking estrogens, it is important that you go to your doctor at least once a year for a physical examination. Also, if members of your family have had breast cancer or if you have breast nodules or abnormal mammograms (breast x-rays), your doctor may w.s. to carry out more frequent examinations of your breasts.

3. Gall bladder disease. Women who use estrogens after menopause are more likely to develop gall bladder disease needing surgery than women who do not use estrogens. Birth control pills have a similar effect.

4. Abnormal blood clotting. Oral contraceptives, some of which contain estrogens, increase the risk of blood clotting in various parts of the body. This can result in a stroke (if the clot is in the brain), a heart attack (clot in a blood vessel of the heart), or a pulmonary embolus (a clot which forms in the legs or pelvis, then breaks off and travels to the lungs). Any of these can be fatal. Blood clots may result in the loss of a limb, paralysis or loss of sight, depending on where the blood clot is formed or lodges if it breaks loose.

The larger doses of estrogen used to prevent swelling of the breasts after pregnancy have been reported to cause clotting in the legs and lungs.

It is recommended that if you have had any blood clotting disorders including clotting in the legs or lungs, or a heart attack or stroke, you should not use estrogens.

SPECIAL WARNING ABOUT PREGNANCY

You should not receive estrogen if you are pregnant. If this should occur, there is a greater than usual chance that the developing child will be born with a birth defect, although the possibility remains fairly small. A female child may have an increased risk of developing cancer of the vagina or cervix later in life (in the teens or twenties). Every possible effort should be made to avoid exposure to estrogens during pregnancy. If exposure occurs, see your doctor.

SOME OTHER EFFECTS OF ESTROGENS

In addition to the serious known risks of estrogens described above, estrogens have the following side effects and potential risks:

1. Nausea and vomiting. The most common side effect of estrogen therapy is nausea. Vomiting is less common.
2. Effects on breasts. Estrogens may cause breast tenderness or enlargement and may cause the breasts to secrete a liquid.
3. Effects on the uterus. Estrogens may cause benign fibroid tumors of the uterus to get larger. Some women will have menstrual bleeding when estrogens are stopped. But if the bleeding occurs on days you are still taking estrogens you should report this to your doctor.
4. Effects on liver. Women taking estrogens develop on rare occasions a tumor of the liver which can rupture and bleed into the abdomen. You should report any swelling or unusual pain or tenderness in the abdomen to your doctor immediately. Women with a past history of jaundice (yellowing of the skin and white parts of the eyes) may get jaundice again during estrogen use.
5. Other effects. Estrogens may cause excess fluid to be retained in the body. This may make some conditions worse, such as epilepsy, migraine, heart disease, or kidney disease.

If any of the above occur, stop taking estrogens and call your doctor.

SUMMARY

Estrogens have important uses, but they have serious risks as well. You must decide, with your doctor, whether the risks are acceptable to you in view of the benefits of treatment. Except where your doctor has prescribed estrogens for use in special cases of cancer of the breast or prostate, you should not use estrogens if you have cancer of the breast or uterus, are pregnant, have undiagnosed abnormal vaginal bleeding, blood clotting disorders including clotting in the legs or lungs, or have had a stroke, heart attack or angina.

You must understand that your doctor will require regular physical examinations while you are taking them and will try to discontinue the drug as soon as possible and use the smallest dose possible. You can help minimize the risk by being alert for signs of trouble including:

1. Abnormal bleeding from the vagina.
2. Pains in the calves or chest or sudden shortness of breath, or coughing blood (indicating possible clots in the legs, heart, or lungs).
3. Severe headache, dizziness, faintness, or changes in vision (indicating possible developing clots in the brain or eye).
4. Breast lumps (you should ask your doctor how to examine your own breasts).
5. Jaundice (yellowing of the skin).
6. Mental depression.
7. Any other unusual condition or problem.

Based on his or her assessment of your medical needs, your doctor has prescribed this drug for you. Do not give the drug to anyone else.

 

Synestrol Interactions

Drug/ Laboratory Test Interactions

Certain endocrine and liver function tests may be affected by estrogen-containing oral contraceptives. The following similar changes may be expected with larger doses of estrogen:

1. Increased sulfobromophthalein retention.
2. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
3. Increased thyroid-binding globulin (TBG) leading to in-creased circulating total thyroid hormone; as measured by PBI, T4 by column, or T4 by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.
4. Impaired glucose tolerance.
5. Decreased pregnanediol excretion.
6. Reduced response to metyrapone test.
7. Reduced serum folate concentration.
8. Increased serum triglyceride and phospholipid concentration.

 

Synestrol Contraindications

Estrogens may cause fetal harm when administered to a preg-nant woman (see

 

Additional information about Synestrol

Synestrol Indication: For use in the treatment of atrophic vaginitis and kraurosis vulvae.
Mechanism Of Action: Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Dienestrol
Synonyms: Dehydrostilbestrol; Dehydrostilboestrol; Dienesterol; Dienoestrol
Drug Category: Estrogens, Non-Steroidal
Drug Type: Small Molecule; Approved

Other Brand Names containing Dienestrol: Agaldog; Cycladiene; Dienoestrol BP; Dienol; Dinestrol; Dinovex; DV; Estragard; Estraguard; Estrodienol; Estroral; Follormon; Gynefollin; Hormofemin; Isodienestrol; Oestrasid; Oestrodiene; Oestrodienol; Oestroral; Oestrovis; Restrol; Retalon; Sexadien; Synestrol; Teserene; Willnestrol; para-Dien;
Absorption: Systemic absorption and mode of action of dienestrol are undetermined.
Toxicity (Overdose): Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.
Protein Binding: 50 to 80%
Biotransformation: Hepatic.
Half Life: Not Available
Dosage Forms of Synestrol: Cream Intravaginal
Chemical IUPAC Name: 4-[4-(4-hydroxyphenyl)hexa-2,4-dien-3-yl]phenol
Chemical Formula: C18H18O2
Dienestrol on Wikipedia: https://en.wikipedia.org/wiki/Dienestrol
Organisms Affected: Humans and other mammals