Tablets for the treatment of endometriosis

Treatment of endometriosis is a long and painstaking process, which, unfortunately, is not always successful. Modern protocols require an integrated approach consisting of surgery and drug therapy. Drugs for the treatment of endometriosis are used independently in cases where surgery is not possible. Hormones or their synthetic analogues are mainly used.

The most popular drugs for the treatment of endometriosis today are:

combined oral contraceptives (COCs)
gonadotropin releasing hormone agonists
synthetic analogues of testosterone and progesterone

Birth control pills

Contraceptives were among the first drugs to treat endometriosis. At first, single-phase progestins containing only gestagens were used. They suppress the processes of proliferation and cyclic changes in the endometrium both in the uterus itself and in endometriotic foci. After some time, sclerosis and regressive development of the lesions are observed. With long-term use, these drugs suppress the synthesis of gonadotropic hormones. As a result, pain and other manifestations of the disease are reduced. The most common side effect of this therapy is irregular bleeding. Today, gestagen drugs have slightly lost their relevance, giving way to estrogen-gestagen drugs.

Among the representatives of this group, the following drugs are currently prescribed:

Duphaston
Norkolut
Premalut

Over time, to reduce side effects and be more effective, COCs containing estrogens and gestagens began to be used. The course involves continuous use for 3-6 cycles of the following drugs:

Janine
Yarina
Diana is 35
Jess
Claira
Dimia

The drugs create a specific hormonal background in a woman’s body that simulates a false pregnancy. The result is approximately the same as when taking gestagens, endometrial proliferation decreases, endometriosis foci become sclerotic and decrease in size, new ones do not appear. In approximately 80% of women, regular use of estrogen-gestagen contraceptives relieves spasms and pain.

Intrauterine devices: advantages and disadvantages

Intrauterine devices are:

hormonal
non-hormonal

Hormonal IUDs have all the advantages and disadvantages of non-hormonal IUDs and, in addition, include the advantages and disadvantages of hormonal contraceptives.

The hormonal intrauterine device deserves separate consideration.

In this article, we will consider in detail the principles of operation, advantages and disadvantages of only non-hormonal IUDs.

Non-hormonal intrauterine devices: mechanisms of action

Mechanisms of action of the spiral:

the spiral affects the composition of cervical mucus , making it thicker, which makes it difficult for sperm to move into the uterus
affects the sperm themselves , reducing their motility
enhances peristalsis of the fallopian tubes (i.e., accelerates the movement of the egg through the tubes), and with accelerated movement, the egg enters the uterus without having time to mature. An immature egg is not able to implant (embed itself) in the uterus.
if fertilization does occur, it prevents the fertilized egg from attaching to the walls of the uterus

The latter property allows the use of an intrauterine device as a means of emergency contraception , which is much safer for the body than the use of special emergency contraceptive pills containing large doses of hormones.

Advantages of non-hormonal intrauterine devices

High degree of protection
– above 95%
Can serve as emergency contraception (however, it must be installed no later than 120 hours (5 days) after unprotected intercourse)
Long service life from 3 to 10 years
depending on the composition of the spiral
occur immediately
after removal of the IUD.
Does not affect a woman’s hormonal levels (there are no problems such as decreased libido, menstrual irregularities, amenorrhea, breast tenderness, mood swings, depression, headaches, nausea, which are inherent in hormonal drugs)
Suitable during lactation (nursing mothers)
Instant effectiveness
(starts working immediately after administration)
Suitable for women with certain diseases when hormonal contraceptives are contraindicated

Disadvantages of non-hormonal intrauterine devices

Insertion and removal is possible only by a gynecologist
It is necessary to check the presence of IUD threads
in the vagina after each menstruation in order to notice spontaneous
loss of the IUD (this happens quite rarely)
More abundant and longer periods in the first few months
after installation of the device
Possible development of endometriosis of the pelvic organs (rare)
Increased risk of developing inflammatory diseases of the uterus and appendages
Installation of the IUD is not recommended for nulliparous
women

Contraindications for installing a spiral

pregnancy
inflammatory diseases of the pelvic organs
malignant growths in the cervix or uterine body
bleeding of unknown etiology (the cause has not been established)
deformation of the uterine cavity for various reasons

Analogues of male hormones for the treatment of endometriosis

Androgen-methyltestosterone analogues are the first drugs for the treatment of endometriosis, which began to be used in the treatment of this disease approximately forty years ago. The main purpose of their use, like contraceptives, is to suppress the menstrual cycle and the associated proliferation of the endometrium. Tablets were prescribed for the treatment of endometriosis at a dose of 5-10 mg for six months. Nowadays, 17a-ethynyl-testosterone derivatives, for example, danazol, are more common from this group. The drug reduces the level of gonadotropic hormone and blocks progesterone, estrogen and androgen receptors in the ovaries.

Danazol has many side effects, including:

weight gain
fatty seborrhea
swelling
acne
mammary atrophy
change in sexual desire
symptoms of menopause (hot flashes, sleep disturbances, irritability, fatigue, depression, cycle irregularities and bleeding between periods)
an increase in the level of low-density lipoproteins in the blood, which increases the risk of cholesterol plaques in the coronary vessels, angina pectoris, and heart attack

Approximately the same side effects occur when taking synthetic progesterone analogues, such as Provera.

Also included in this group are drugs such as:

Duphaston (dydrogesterone)
Visanne (dienogest)
Orgametril (linestrenol)

The duration of taking the drugs is 6-8 months. Quite often, after completing the course, women experience relapses. Now this group of drugs is rarely used, they have been replaced by birth control pills for the treatment of endometriosis and more modern drugs.

Silhouette

Use during pregnancy and breastfeeding

Siluet® is contraindicated during pregnancy.
If pregnancy occurs while taking Siluet®, use of the drug should be stopped immediately. The available information regarding the use of the drug Siluet® during pregnancy is too limited to draw conclusions about the negative effects of the drug Siluet® on pregnancy, the health of the fetus and the newborn. Extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who took sex hormones for contraception before pregnancy or through negligence in early pregnancy.

Use for liver dysfunction

Use caution in case of liver dysfunction.

Use for renal impairment

With caution in case of impaired renal function.

special instructions

Before starting or resuming taking Siluet®, it is necessary to obtain an anamnesis (including family history), and it is also necessary to exclude pregnancy. It is necessary to measure blood pressure and conduct a general examination, taking into account contraindications and precautions. It is necessary to explain to the woman the need to carefully read the instructions for use of the drug Siluet® and follow the recommendations contained therein. The nature of medical examinations, including general medical and gynecological examinations, is determined by the attending gynecologist individually for each woman and is carried out at varying frequencies, but at least once every 6 months. A woman should be warned that oral contraceptives do not protect against HIV infection (AIDS) or any other sexually transmitted disease.

Reduced efficiency

A decrease in the effectiveness of the combination of ethinyl estradiol and dienogest occurs in the case of, for example, a missed dose, gastrointestinal disorders or when taking concomitant therapy.

Change in bleeding pattern

The use of the drug Siluet®, especially in the first three cycles, may be accompanied by the appearance of acyclic spotting/bleeding from the vagina, which can be considered as an adaptation period.

If irregular bleeding is persistent or appears after previous normal regular cycles, non-hormonal causes should be considered and malignancy and pregnancy excluded. In this case, you need to consult a gynecologist.

Some women have "acute belly" bleeding.

The risk of venous thromboembolic complications increases:

with age;
in the presence of a family history (venous thromboembolism that has ever occurred in close relatives and parents at a relatively young age); if a congenital predisposition is possible, the woman should be referred to a specialized specialist to decide on the prescription of the drug Siluet®;
during prolonged immobilization, after major surgery, any surgery on the lower extremities or after serious trauma. In these cases, it is preferable to stop taking the tablets (for elective operations at least four weeks in advance) and not resume until two full weeks have passed after remobilization. If the drug has not been discontinued in advance, antithrombotic therapy should be prescribed;
for obesity (BMI more than 30 kg/m2).

There is no consensus on the role of varicose veins or thrombophlebitis of superficial veins in the occurrence and development of venous thrombosis.

The risk of arterial thromboembolic complications or the risk of stroke in women using the combination of ethinyl estradiol and dienogest is increased:

with age;
in the presence of dyslipoproteinemia;
in the presence of arterial hypertension;
for diseases of the heart valves;
with atrial fibrillation;
when smoking: smokers increase the risk of severe cardiovascular complications (such as myocardial infarction, stroke); The risk increases with age and the number of cigarettes smoked.

The presence of one severe or several risk factors for the development of venous or arterial diseases, respectively, may also be a contraindication. The possibility of using anticoagulant therapy should also be considered. Women receiving Siluet® should be advised to contact their doctor if symptoms of thrombosis are suspected. In case of suspected or proven thrombosis, the drug should be discontinued. In this case, women need to use other suitable methods of contraception due to the teratogenic effect of anticoagulant drugs (coumarins).

The increased risk of thromboembolism during the postpartum period must be taken into account.

Other conditions associated with adverse vascular reactions include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, and chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis).

An increase in the frequency and severity of migraine when taking a combination of ethinyl estradiol and dienogest (which may be a harbinger of cerebrovascular accident) may be an indication for immediate discontinuation of the drug.

Tumors

Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of the combination of ethinyl estradiol and dienogest (more than 5 years). However, controversy remains about the extent to which these cases are related to sexual behavior and other factors, such as human papillomavirus (HPV).

Studies have shown a slight increase in the relative risk (RR = 1.24) of developing breast cancer in women who used COCs. The increased risk gradually decreases over 10 years after stopping these drugs.

In rare cases, the development of benign liver tumors has been observed during the use of a combination of ethinyl estradiol and dienogest, and in even more rare cases, malignant ones. In some cases, these tumors have led to life-threatening intra-abdominal bleeding. If severe pain appears in the upper abdominal region, liver enlargement and signs of intraperitoneal bleeding in women taking combinations of ethinyl estradiol and dienogest, liver tumors should be excluded.

Other states

Women with a current or history of hypertriglyceridemia are at increased risk of developing pancreatitis when using the combination of ethinyl estradiol and dienogest. Although slight increases in blood pressure have been described in many women taking combinations of ethinyl estradiol and dienogest, clinically significant increases have been reported rarely. However, if women with arterial hypertension experience a stable increase in blood pressure while taking COCs, or if sudden increases in blood pressure do not respond to antihypertensive therapy, the drug should be discontinued. If possible, treatment can be continued if normal blood pressure values are achieved with antihypertensive therapy.

Acute or chronic liver disease may require discontinuation of Siluet® until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of the combination of ethinyl estradiol and dienogest.

Although the combination of ethinyl estradiol and dienogest may have an effect on tissue resistance to insulin and glucose tolerance, there is usually no need to adjust the treatment regimen in patients with diabetes. However, women with diabetes should be under close medical supervision while taking Siluet®.

The use of a combination of ethinyl estradiol and dienogest may worsen the course of Crohn's disease and ulcerative colitis.

Chloasma may appear periodically, especially in women with a history of chloasma during pregnancy. Women prone to chloasma should avoid prolonged sun exposure and exposure to ultraviolet radiation while taking Siluet®.

Laboratory research

The use of contraceptive steroids may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, as well as plasma levels of transport proteins, for example, corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, as well as coagulation and fibrinolysis. Changes usually remain within normal limits.

Impact on the ability to drive vehicles and operate machinery

The drug Siluet® does not affect the ability to drive a car or use complex equipment. When using the drug, the possibility of visual impairment or dizziness should be taken into account.

Gonadotropin releasing hormone agonists as drugs for the treatment of endometriosis

This group of drugs is a synthetic analogue of pituitary releasing hormones, which are responsible for the synthesis of latinizing and follicle-stimulating hormone. Their decrease in the blood causes a decrease in the production of progesterones by the corpus luteum of the ovaries in the second half of the cycle. As a result, there is no proliferation of the endometrium in endometriotic lesions. Estrogen levels also decrease, leading to a state of artificial reversible menopause. The drugs are administered by injection daily or once every 28 days under the skin of the abdomen. There are medications in the form of sprays that are sprayed into the nose.

The most well-known drugs for the treatment of endometriosis from this group are:

Leuprolide acetate or Lupron
Nafarelina acetate or Sinarel
Goserelin acetate or Zoladex.

Although today gonadotropin releasing hormone agonists are considered the most acceptable for drug therapy for endometriosis, their side effects are quite serious. First of all, these are symptoms of menopause. It includes:

tides
irritability
sleep disorders
decreased performance
mood swings up to depression
weight gain
limb cramps and signs of osteoporosis due to impaired calcium absorption
increased risk of angina and heart attack

In rare cases, menopause may be irreversible. Medicines in this group are not recommended to be taken for more than six months in a row.