Medicines Used For Uterine Fibroids

2024 Author: Josephine Shorter | [email protected]. Last modified: 2024-01-07 17:49

Medicines used for uterine fibroids

Suspicions of uterine fibroids should not be cause for panic. If during the examination there are reasons for concern - do not be discouraged, wait for the next menstruation and try to undergo an ultrasound scan again. In this case, it is desirable that the study is carried out using a vaginal sensor. And even when the diagnosis is confirmed, it is worth checking it with another gynecologist for accuracy.

A uterine fibroid is a benign tumor that occurs in the muscle layer and walls of the body or cervix. It is a collection of nodules of proliferating smooth muscle cells. Often, cell proliferation appears in several places at once and reaches sizes from a couple of millimeters to ten to twenty centimeters. The size of the fibroid is measured by gynecologists not in the metric system, but by analogy with the increase in the uterus during pregnancy - in weeks.

In the early stages (up to 12 weeks), with slow growth and the absence of symptoms, conservative treatment of fibroids is possible. This is especially facilitated by the state of premenopause - the approach of menopause, when the first signs of menopause appear. At this time, due to the inhibition of natural hormonal processes, tumor growth is greatly slowed down until it stops completely. Non-surgical treatment of leiomyoma consists in taking medications of various types, which will be discussed in the following sections of this article.

Content:

• COCs (combined oral contraceptives)
• Gonadotropin-releasing hormone agonists
• Antiprogestogens
• Antigonadotropins
• Gestagens
• HRT - hormone replacement therapy
• Intrauterine device Mirena with myoma
• Recent Research

COCs (combined oral contraceptives)

Drugs in this group are drugs of various dosage forms based on hormones. To reduce the size of the tumor, the following combinations of hormones are required:

Ethinyl estradiol with desogestrel

This combination is present in preparations:

• Mercilon;
• Novinet;
• Marvelon.

Ethinylestradiol and norgestrel

Together, these hormones are found in medications such as:

• Ovidon;
• Rigenidone.

Ethinylestradiol with Gestodene

This combination is used in preparations:

• Logest;
• Lindineth.

Thanks to the intake of these pharmaceuticals, it is possible to stop the symptoms of uterine fibroids such as bleeding and lower abdominal pain. However, it is possible to reduce tumors, in most cases, only if the size of the fibroid does not exceed a diameter of one and a half centimeters. Because of this, combined oral contraceptives are not a priority in the treatment of fibroids.

Gonadotropin-releasing hormone agonists

Mechanism of action: gonadotropin-releasing hormone agonists initiate temporary pharmacological menopause by inhibiting the synthesis of gonadotropins. This is due to the binding of a-GnRH to the gonadoliberin receptors in the adenohypophysis. With continuous administration, they cause the complete disappearance of these receptors from the pituitary cell membranes, which provokes a blockade of gonadotropin secretion, which is temporary and reversible, although it is accompanied by amenorrhea.

This group includes funds based on such hormones:

• Triptorelin. Present in the drugs Decapeptil, Dipherelin and Decapeptyl-depot. In the usual form, it is required to inject subcutaneously once a day - 0.5 mg in the first week and 0.1 mg for the next three weeks. Triptorelin acetate in depot form is injected on the 3rd day of the menstrual cycle at a dose of 3.75 mg, then every 28 days for six months.
• Goserelin. It is presented in the preparation Zoladex in depot capsules with a dosage of 3.6 mg and similar extended-release capsules of 10.8 mg. Deep intramuscular or subcutaneous injection into the shoulder, buttocks or abdomen. The course starts from 2-4 days of the menstrual cycle, 3.6 mg every 28 days. The duration of the course is from 4 to 6 months.
• Nafarelin. It is used as part of Sinarel endonasal spray at a dosage of 400 to 800 mcg per day. Daily insufflation of 200 mcg of nafarelin acetate.
• Buserelin. The dosage form is a Buserelin nasal spray dosage containing 2100 mg of buserelin acetate, which corresponds to 2 g of buserelin. One full press of the pump gives 150 mcg of buserelin, a daily dose of 900 mcg.

• Leiprorelin. The drug Lukrin-depot is available in the form of a powder in vials or two-chamber syringes for preparing a suspension. Intramuscular or subcutaneous injection, dosage - 3.75 mg of leuprorelin acetate in each injection.

When treated with gonadotropin-releasing hormone agonists, an average decrease in fibroid volumes is observed by 52.6%. However, in 5-18% of cases, GnRH a therapy does not give visible results. With multiple fibroids, the degree of regression of several tumors in one patient is most often different. Various researchers cite the reasons for this variability as the age of the patients and the uneven distribution of fibrous and smooth muscle components in the myoma, as well as degenerative changes in the tumor and loss of sensitivity to antiestrogenic effects.

In most cases, the full effect of GnRH-α treatment is observed at 3-4 months of therapy with a slow extinction by the sixth month. Sometimes, after 50-68% of tumor regression at 4 months with a standard prolongation of therapy up to six months, a secondary increase in myoma begins, leading to a return of 80-100% of its original size. The negative side of the use of agonists are also side reactions associated with hypoestrogenism: depression, lability, decreased libido, hot flashes and bone demineralization.

Various strategies are proposed to combat side effects:

• The add-back regimen involves the addition of low-dose estrogen agonist therapy, which raises estradiol levels to a threshold at which fibroid growth is not yet resumed, but the side effects of hypoestrogenism are not observed or are greatly reduced.
• on-off mode means an intermittent course of GnRH agonists - 3/3 months of admission. After a 3-month break in therapy, endogenous estrogen production is fully restored, but the increase in uterine volume is minimal in most cases.
• The interval mode allows you to maintain an adequate rate of myoma regression with almost complete absence of symptoms of hypoestrogenism by gradually increasing the standard interval of GnRH a-intake from 28 to 70 and 84 days (10-12 weeks).
• The drow-back mode was invented by researchers who, by dramatically reducing the dose of the agonist from 100 mg / day to 5-20 mg / day after reaching the limit at which pronounced hypoestrogenism is manifested (from about 2 months of therapy), achieved the preservation of the effect of reducing fibroids with partial restoration of estrogen synthesis over the next 18 weeks.

Thus, gonadoliberin agonists are a fairly effective tool for the non-surgical treatment of uterine fibroids during the premenopausal period and earlier, if we use innovative methods of their application. With large tumor sizes, they significantly help facilitate surgical intervention, allowing the use of modern technologies of sparing reconstructive operations.

It should be separately noted the useful properties of agonists in the treatment of fibroids in patients with anemia and metrorrhagia, which can reduce the risk of surgery, restore blood counts and create a blood bank for the purpose of autodonation.

On the subject: Surgery to remove uterine fibroids - is it needed? Complications and consequences

Antiprogestogens

Mifepristone - blocks the effect of progesterone by binding to gestagen receptors. Available in 200 mg tablets, 3-6 pieces per package. The drug is a means for medical termination of pregnancy (up to 9 weeks), an auxiliary medicine for dilating the cervix during abortion up to 12 weeks and potentiating the work of prostaglandins for abortion from 13 to 22 weeks. With uterine myoma, it promotes short-term regression of tumor nodes and elimination of symptoms, therefore it is used for preoperative therapy.

Antigonadotropins

They are used only if other pharmacological agents are powerless. The group includes drugs with such active ingredients as:

• Danazol. Contained in the preparations Danazol, Vero-Danazol, Danol, Danoval, Danogen.
• Gestrinone. The basis of the drug Nemestran.

Antigonadotropins are used extremely rarely, since they can only level the symptoms of fibroids, but do not affect the size of the tumor itself. In addition, drugs from this class provoke acne and hypertrichosis (excessive hair growth) with voice changes.

Gestagens

Relatively effective and inexpensive means, due to which they are still used in gynecology, although in many cases this effectiveness has not been proven.

Mechanism of Action: Taken to block the synthesis of estrogen by the ovaries. In comparison with a-GnRH, an insufficient degree of inhibition of estrogen production is observed. To enhance the action, a strong excess of progesterone in the blood is required in the luteal phase of the cycle, which blocks the process of hyperplasia with hypertrophy of biogenic elements of fibroids, which stimulates cell degeneration in the central part of tumor nodes.

• Norkolut - 5 mg tablets of norethisterone. The dose should be calculated by the doctor taking into account the tolerability and observed effectiveness of the drug. The standard course consists of a daily intake of 1 tablet of the drug on days 5-25 of the cycle for six months.
• Duphaston - tablets with 10 mg of dydrogesterone. One tablet is prescribed 2-3 times a day, either from 5 to 25 days of the cycle, or constantly. The course lasts from 3 months to six months - at the end there should be a pronounced therapeutic effect - tumor regression and the absence of fibroid symptoms.
• 17-OPK is a preparation based on 17-hydroxyprogesterone caproate. Available in 1 ml ampoules as part of an oil solution with a concentration of 12.5 and 25% (0.125 and 0.25 g, respectively). For the development of endometrial atrophy with subsequent regression of fibroids, deep intramuscular injection of 500 mg of the drug is used in two approaches per week for a period of 3 to 6 months.

Unfortunately, hopes for a complete or at least significant reduction of leiomyoma nodes during therapy with progesterone analogues are not fully justified. In some cases, the patient's condition even worsened. It has been scientifically established that progestins, due to an increase in the mitotic index in the luteal phase of the cycle, may even contribute to the proliferation of fibroids.

HRT - hormone replacement therapy

Hormone replacement therapy can help relieve the symptoms of menopause in women, reduce the likelihood of heart disease, and prevent bone destruction and vaginal atrophy. Hormonal therapy reduces the overall mortality of women during menopause and corrects disorders associated with menopause.

The question of the use of hormone therapy drugs in women in menopause is controversial: during menopause, the growth of benign tumors stops, and uterine myoma does not progress, however, the body's response to hormonal drugs is unpredictable.

According to clinical observations by A. Senez, the diameter of myomatous nodes during treatment with conjugated estrogen (0.625 mg) and medroxyprogesterone (2.5 mg) did not change during the year. However, when the dose of gestagen was doubled, the size of the nodes became larger. Thus, treatment with progesterone drugs affects the growth of benign tumors to a greater extent than estrogen drugs. Other authors note that the growth of myoma nodes, as well as changes in the size and volume of the uterus, were not detected during the use of cyclic drugs.

Differences in the effect of progestins in cyclic hormone replacement therapy depend on the pharmacological characteristics of the drugs. It is recommended to prescribe progestogens with an antiproliferative effect as HMG (hormone replacement therapy) for women in the climacteric period. These include drugs such as Trisequencing and Cliogest.

On the subject: Borovaya uterus and red brush with uterine fibroids

Intrauterine device Mirena with myoma

Most of the intrauterine devices are not used to treat any disease. But one of them, the hormonal coil of Mirena, has been found to have properties that help to cope with a number of symptoms characteristic of uterine fibroids.

Mirena acts locally, gradually releasing levonorgestrel in low doses only within the uterus. The daily intake of this hormone helps to reduce the amount of blood secreted during menstruation and relieve pain in the lower abdomen. Due to the fact that it practically does not enter the bloodstream, the general condition of the body does not change for all 5 years that it is possible to wear this spiral.

The Mirena intrauterine therapeutic system, moreover, prevents unwanted pregnancies without impairing fertility. A year after the removal of the spiral, 80% of women who wanted to have children develop a pregnancy.

Recent Research on Drug Treatment

Scientists from Belgium have made significant progress in solving the problem of treating uterine fibroids. They were interested in research data, which indicated that not only estrogen, but also progesterone is responsible for the rapid growth and development of uterine fibroids. This prompted scientists to study the properties of drugs that can block the effect of gestagens. The Brussels team of scientists at the St. Luke Hospital found the urgent contraceptive pills containing ulipristal acetate especially interesting.

As it turned out, this active substance is a modulator of progesterone receptors. On its basis, the drug Esmya was created.

The first clinical trial (double randomized placebo) involved 550 women preparing for surgery to remove uterine fibroids. After three months in the group taking Esmya tablets, there was a significant decrease in the size of the tumor, as well as getting rid of the symptoms of fibroids.

In conclusion, the researchers published the following results:

• In 90% of women, the intensity of bleeding and the volume of leiomyoma decreased.
• 50% of patients were given the opportunity to refuse surgery.
• The results obtained by the principle of action are comparable to therapy with hormone blockers, but, unlike them, Esmya does not cause hot flashes and degeneration of bone tissue.
• After a 6-month course of blockers, the tumor usually partially or completely returns to its size, which was not observed even six months after taking Esmiya.

Research carried out by Belgian scientists has provided a real opportunity to solve the issue of treating uterine fibroids with one remedy, without side effects and complex procedures.

The author of the article: Lapikova Valentina Vladimirovna | Gynecologist, reproductologist

Education: Diploma in Obstetrics and Gynecology received at the Russian State Medical University of the Federal Agency for Healthcare and Social Development (2010). In 2013 completed postgraduate studies at N. N. N. I. Pirogova.