Composition of Ovestin
The main component of Ovestin is estriol. This is a hormone, the deficiency of which in the body affects the condition of the mucous membranes of the genitourinary system. For suppositories, an additional component is vitepsol, as the most common base for the production of suppositories.
Other auxiliary components are used for the cream to achieve a soft absorbent texture: glycerol, lactic acid, sodium hydroxide, octyldodecanol, sorbitan stearate, purified water.
The effectiveness of both forms of the drug is due to the presence of estriol.
Action of Ovestin
Ovestin is indicated for women during menopause. At this time, a woman’s body undergoes a radical restructuring, the level of hormone production changes, which affects both mood and well-being. Menopause is often accompanied by hot flashes - sudden sweating. At this time, the woman experiences discomfort for most of the day. She may be tormented by a headache, unreasonable irritability, a feeling of cold or, conversely, stuffiness in the room. All this is complemented by physical discomfort in the intimate area.
Due to an imbalance of hormones, the mucous membranes of the genital organs cannot cope with the function of moisturizing. This causes itching and even burning in the groin. Ovestin successfully combats these symptoms. Working locally, it does not allow the vaginal walls to dry out, which means it increases local immunity. Thanks to this, it is possible to avoid infection with sexually transmitted infections that cause vaginitis, urinary incontinence and inflammation of the genitourinary tract.
Using Ovestin restores the joy of life, relieves discomfort and pain during sexual intercourse. A woman forgets about itching and burning in the intimate area, which means there are fewer reasons for irritability.
Instructions for use
It is recommended to use suppositories once a day, preferably at night. During 6-8 hours of sleep, the hormone from the suppositories is released and replenishes the estrogen deficiency.
If the prescription of Ovestin is associated with the treatment of atrophy of the mucous membranes of the vagina and urinary tract, the following treatment regimen is indicated: one suppository every night for two weeks. With a clear decrease in symptoms, reduce the dose and gradually increase to 2 suppositories per week.
If a woman who has reached the age of menopause is being prepared for surgery, two weeks before the intervention, 1 suppository is prescribed daily. After surgery, it is necessary to continue treatment at a dosage of 1 suppository twice a week for 14 days.
When diagnosis through a cytological smear is difficult, 1 suppository is prescribed every other day for a week before taking the material.
Important! If a woman has forgotten to put the suppository on schedule, she needs to continue treatment from the day she remembered to take her course. It is not permissible to make up for missed doses by increasing the daily dosage. After an accidental break, therapy is continued as before.
Instructions for use OVESTIN® (OVESTIN)
To treat menopausal symptoms, HRT should only be started for symptoms that adversely affect quality of life. In all cases, it is necessary to conduct a thorough assessment of the risks and benefits of treatment at least once a year, and HRT should be continued only for a period of time until the benefits outweigh the risks.
Before starting or resuming HRT, a detailed individual and family history should be established. Based on the obtained medical history, contraindications and warnings for use, it is necessary to conduct a clinical examination (including examination of the pelvic organs and mammary glands). During treatment, it is recommended to conduct periodic medical examinations, the frequency and nature of which vary from person to person. Women should be informed about the need to report changes in the mammary glands to their doctor. Tests, including mammography, must be performed in accordance with currently accepted screening standards.
Therapy should be discontinued if a contraindication is identified and if the following conditions occur:
- jaundice or impaired liver function, significant increase in blood pressure, resumption of migraine-type headaches, pregnancy, endometrial hyperplasia.
When used intravaginally to prevent stimulation of the endometrium, the daily dose should not exceed 0.5 mg of estriol (1 application of cream or 1 suppository). This maximum dose should not be used for more than 4 weeks.
Breast cancer
Based on randomized, placebo-controlled, Women's Health Initiative (WHI) trials, and epidemiological studies including the Million Women Study (MWS), an increased risk of breast cancer was reported in women taking estrogens, estrogen-progestogen combinations, or tribolone. for HRT for several years. For all HRT, the increased risk becomes noticeable after several years of use and increases with duration of use, but returns to baseline levels a few (maximum 5) years after stopping treatment.
In the MWS study, the relative risk of mammary cancer with conjugated equine estrogens (CEE) or estradiol (E2) was higher when a progestogen was added, both cyclically and continuously, and regardless of the type of progestogen. There is no evidence of differences in risk between different routes of administration.
In the WHI study, a continuous combination of conjugated equine estrogen and medroxyprogesterone acetate (CEE + MPA) was associated with mammary tumors that were slightly larger and more likely to have local lymph node metastases compared with placebo.
It is unknown whether such a risk is associated with the use of Ovestin. A recent population-based case-control study of 3345 women with invasive breast cancer and 3454 controls showed that estriol use, unlike other estrogens, was not associated with an increased risk of breast cancer. Therefore, when deciding whether to use HRT, it is very important to carefully assess the risk of developing breast cancer and the benefits of therapy.
Venous thromboembolism (VTE)
HRT is associated with a higher relative risk of developing VTE - deep vein thrombosis or pulmonary embolism. One randomized controlled trial and epidemiological studies have found that the risk for women receiving HRT is 2-3 times higher than for non-users. It is unknown whether the use of Ovestin is associated with the same risk.
Commonly recognized risk factors for VTE include personal or family history, severe obesity (BMI >30 kg/m2) and systemic lupus erythematosus. There is no consensus regarding the possible role of varicose veins in the development of VTE.
Patients with a history of VTE or known thromboembolic conditions are at increased risk of VTE. HRT may increase this risk. In order to exclude a predisposition to blood clots, it is necessary to examine an individual and family history of thromboembolism or recurrent spontaneous miscarriage. Until a thorough assessment of thromboembolic factors has been carried out, the initiation of anticoagulant treatment or the use of HRT in such patients should be considered a contraindication. For women already receiving anticoagulant treatment, careful consideration of the benefit-risk balance of HRT is required.
The risk of VTE may increase with prolonged immobilization of the patient, extensive trauma, or a large volume of surgical intervention. After surgery, special attention should be paid to preventive measures to prevent VTE. In cases where prolonged immobilization is unavoidable after elective surgery (especially after abdominal surgery or orthopedic surgery on the lower extremities), if possible, temporary cessation of HRT should be considered 4-6 weeks before surgery. If the drug Ovestin is used for indications related to pre- and postoperative therapy, then it is necessary to provide preventive treatment to prevent thrombosis.
If VTE develops after starting treatment with Ovestin, treatment should be discontinued. Patients should be advised to seek immediate medical attention if they experience a symptom of a potential thromboembolism (eg, painful leg swelling, sudden chest pain, shortness of breath).
Cardiac ischemia
Randomized controlled trials have not confirmed the positive effect of continuous use of a combination of conjugated estrogens and medroxyprogesterone acetate on the state of the cardiovascular system. Two large clinical trials (WHI and HERS, i.e. Heart Study and Estrogen-Progestogen Replacement Therapy) showed a possible increase in the risk of cardiovascular disease during the first year of use and did not show an overall benefit. For other HRT drugs, only limited data are available from randomized controlled trials assessing effects on cardiovascular disease incidence or mortality in such patients. Therefore, it is not certain that these results also apply to other HRT drugs.
Stroke
It was found that there is an increased risk of ischemic stroke in healthy women during treatment with continuous use of a combination of conjugated estrogens and medroxyprogesterone acetate. It is unknown whether this risk applies to other HRT drugs, including Ovestin.
Ovarian cancer
Long-term (at least 5-10 years) use of estrogen-only HRT in women who have had uterine surgery has been associated with an increased risk of ovarian cancer in several epidemiological studies. There is no certainty that long-term use of combined HRT or low-potency estrogens (for example, Ovestin) is characterized by a different degree of risk than the use of drugs containing only estrogen.
Other states
Estrogens can cause fluid retention and therefore patients with impaired renal function and cardiovascular insufficiency should be closely monitored. Patients with end-stage chronic renal failure should be closely monitored as circulating levels of the active substances of Ovestin are expected to increase.
Estriol is a weak gonadotropin inhibitor and has no other significant effects on the endocrine system.
There has been no convincing evidence of improvement in cognitive function with HRT.
In case of vaginal infections, concomitant specific treatment is recommended.
Ovestin cream - instructions
The use of the cream is made easier by the included applicator. It helps to dose the cream correctly for one-time use of the product. To measure out 0.5 g of cream, just pour it into the applicator up to the special mark.
When treating atrophy of the mucous membranes, 1 dose of cream is administered using an applicator at night. It is permissible to use the product daily for a month. After the fourth week of use, gradually reduce the dose to 1 twice a week.
Before the scheduled operation, take 1 dose every evening for two weeks. In the postoperative period, reduce the dosage to 1 application twice a week. Therapy is continued for 14 days.
Before performing a cytological examination of the cervix, 1 application is administered every other day a week before taking the material.
When using this form of Ovestin, do not forget that the applicator must be rinsed under running water after each use. It is unacceptable to boil water to disinfect the applicator.
Ovestin®
— To treat menopausal symptoms, HRT should only be prescribed for symptoms that adversely affect quality of life. In all cases, a thorough assessment of the risks and benefits of treatment should be carried out at least once a year, and HRT should be continued only as long as the benefits outweigh the risks.
— There is limited evidence of the risks of HRT when treating premature menopause. Due to the lower absolute risk in younger women, the benefit-risk ratio is more favorable in them than in older women.
Medical examination/observation
— Before starting or resuming HRT, it is necessary to obtain a detailed individual and family history. Guided by the obtained medical history, contraindications and warnings for use, it is necessary to conduct a clinical examination, including examination of the pelvic organs and mammary glands. During treatment, it is recommended to conduct periodic medical examinations, the frequency and nature of which vary from person to person. Women should be informed about the need to tell their doctor about changes in the mammary glands (see “Breast cancer” below). Investigations, including appropriate imaging modalities such as mammography, should be performed in accordance with currently accepted examination standards and on a case-by-case basis.
Reasons for immediate discontinuation of therapy:
Therapy should be discontinued if contraindications are identified and if the following conditions occur:
- Jaundice or deterioration of liver function;
- Significant increase in blood pressure;
— The occurrence of migraine-type headaches;
- Pregnancy.
Endometrial hyperplasia and carcinoma
— To prevent stimulation of the endometrium, the daily dose of the drug should not be divided into several doses and should not exceed 8 mg of estriol. In addition, one epidemiological study found that long-term use of low-dose estriol may increase the risk of endometrial cancer. The risk increases with the duration of treatment and returns to baseline values one year after discontinuation of the drug. Basically, the risk of minimally invasive and well-differentiated tumors increases.
For women with an intact uterus, the following precautions are recommended:
- The entire daily dose must be taken at once;
— The patient should be informed of the need to contact the attending physician if vaginal bleeding begins (this symptom in all cases requires examination);
- With long-term treatment, the condition of the endometrium must be assessed at least once a year, or progestogens must be prescribed for at least 12-14 days of each calendar month.
When deciding whether to control the condition of the endometrium or to prescribe progestogens, the increased risk of breast cancer with combined therapy with estrogens and progestogens should be taken into account. There is currently no evidence that estrogen monotherapy increases the risk of breast cancer.
Mammary cancer
— Hormone replacement therapy may increase mammographic density. This can make radiological detection of breast cancer more difficult. Clinical studies have shown that the likelihood of developing increased mammographic density was lower in patients treated with estriol than in patients treated with other estrogens.
— Pooled evidence suggests an increased risk of breast cancer in women receiving combination therapy with estrogens and progestogens and possibly estrogen monotherapy.
— In women receiving combination therapy with estrogens and progestogens for more than 5 years, there was a 2-fold increase in the risk of breast cancer.
— With estrogen monotherapy, any increase in risk is significantly lower than when combined with progestogens.
— The level of risk depends on the duration of HRT.
— It is unknown whether Ovestin® poses the same risk. A recent population-based case-control study of 3345 women with invasive breast cancer and 3454 controls showed that estriol use, unlike other estrogens, was not associated with an increased risk of breast cancer. It is therefore important that the risk of developing breast cancer is discussed with the patient and weighed against the known benefits of HRT.
Ovarian cancer
— Ovarian cancer develops much less frequently than breast cancer. Long-term estrogen monotherapy (at least 5-10 years) was associated with a small increase in the risk of ovarian cancer. Some studies suggest that combined HRT may increase the risk of ovarian cancer in a similar or small way. It is not known whether the risk of long-term use of low-potency estrogens (such as Ovestin®) differs from that of monotherapy with other estrogens.
Venous thromboembolism
— HRT is associated with an increased risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism, 1.3 - 3 times. VTE is more likely to occur during the first year of HRT use than later in life. A similar risk is not known for Ovestin®.
— In patients with confirmed thrombophilia, the risk of VTE is high, and HRT may further increase it. In this regard, HRT is contraindicated for such women (see section “Contraindications”).
— Commonly recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus, and cancer. Not regarding the possible role of varicose veins in the development of VTE. After any surgical intervention, VTE prophylaxis is necessary. If prolonged immobilization is associated with elective surgery, it is necessary to temporarily discontinue HRT 4-6 weeks before surgery. Treatment should be resumed after the woman begins to walk.
— If Ovestin® is prescribed as “pre- and postoperative treatment,” the issue of thrombosis prevention should be considered.
— In the absence of a history of VTE, but in the presence of thrombosis at a young age in the patient’s closest relatives, she can be offered a screening examination, having previously discussed all its limitations (screening can only identify a number of thrombophilic disorders). If a thrombophilic defect is detected that does not correspond to the disease in relatives, or if a “severe” defect is detected (for example, deficiency of antithrombin, protein S or protein C, or a combination of these defects), HRT is contraindicated.
— For women already receiving anticoagulant treatment, careful consideration of the benefit-risk ratio of HRT is required.
— If VTE develops after starting treatment with Ovestin®, then treatment with the drug must be stopped. Patients should be informed to seek immediate medical attention if they experience possible signs of thromboembolism (eg, painful leg swelling, sudden chest pain, shortness of breath).
Coronary heart disease (CHD)
— In randomized controlled trials, there were no results that would indicate that combination therapy with estrogens and progestogens and estrogen monotherapy can prevent the development of myocardial infarction in women with and without coronary artery disease.
Estrogen monotherapy:
— According to randomized controlled trials in women with a removed uterus, the risk of coronary heart disease does not increase with estrogen monotherapy.
— The risk of coronary heart disease increases slightly with combined HRT with estrogens and progestogens in patients over 60 years of age.
Ischemic stroke
— Combination therapy with estrogens and progestogens and monotherapy with estrogens are associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with age or time after menopause. However, the baseline risk of stroke is highly dependent on age, and the overall risk of stroke with HRT increases with age. The risk of hemorrhagic stroke does not increase with HRT;
Other states
— Estrogens can cause fluid retention, so patients with impaired renal function and cardiovascular insufficiency should be under close medical supervision.
— Estriol is a weak gonadotropin antagonist and does not have other significant effects on the endocrine system.
— Cognitive function does not improve with HRT. Evidence was obtained of an increased risk of developing dementia in women who began using combination therapy or monotherapy in a continuous mode after 65 years of age.
Possible side effects of Ovestin
Ovestin cream, like suppositories, when in contact with the mucous membrane of the female genital organs, can cause mild irritation and even burning. As a rule, this feeling passes. Replenishment of the lack of hormones is neutralized, and along with it, the unpleasant sensations associated with the administration of the very first dose of the drug disappear.
When it comes to hormone therapy, there is always a risk of developing cancer. Ovestin, if dosed incorrectly and if the dosage regimen is not followed, can cause endometrial cancer or malignant neoplasms of the mammary gland. In addition, non-cyclical bleeding may occur.
Ovipol Klio
HRT for the treatment of symptoms of estrogen deficiency should be carried out only for symptoms that adversely affect the woman’s quality of life. At least once a year, a thorough assessment of the benefit-risk ratio should be carried out; continuation of therapy is justified only if the benefit of using the drug exceeds the risk. There is limited evidence of the risks associated with HRT when treating premature menopause. Due to the low absolute risk in younger women, their benefit-risk ratio is more favorable than in older women.
Medical examination/observation
Before starting or resuming HRT after its interruption, it is necessary to collect a detailed individual and family history, conduct a general and gynecological examination (including examination of the mammary glands and pelvic organs). During the therapy period, it is recommended to conduct periodic medical examinations, the frequency and nature of which are determined individually. The woman should be informed about the need to inform the doctor about possible changes in the mammary glands. Screenings, including appropriate imaging modalities such as mammography, should be performed according to currently accepted screening standards and on a case-by-case basis.
Reasons for immediate discontinuation of therapy:
Therapy should be stopped immediately if a contraindication is identified and if the following conditions occur:
- jaundice or deterioration of liver function;
- significant increase in blood pressure;
- the occurrence of migraine-type headaches;
- pregnancy.
Hyperplasia and endometrial cancer
To prevent stimulation of the endometrium, the daily dose of estriol should not exceed one administration (0.5 mg of estriol) per day. This maximum dose should not be used for more than 4 weeks. One epidemiological study found that long-term, low-dose oral estriol may increase the risk of endometrial cancer. The risk increases with the duration of treatment and returns to baseline values one year after discontinuation of the drug. Basically, the risk of developing minimally invasive and highly differentiated tumors increases. If spotting/bleeding from the vagina occurs, an appropriate examination is necessary. The patient should be informed of the need to contact the attending physician if bleeding begins.
Mammary cancer
Long-term use of HRT increases the risk of developing breast cancer in women receiving combination therapy with estrogen and progestogen and, possibly, estrogen monotherapy. In women receiving combined estrogen + progestogen therapy for more than 5 years, there was a 2-fold increase in the risk of developing breast cancer.
With estrogen monotherapy, the increase in risk is significantly lower than when combined with a progestogen. Limited data indicate that there is no risk of developing breast cancer with the use of estriol.
HRT, particularly combination drugs, may increase the density of mammographic images. This may complicate radiological detection of breast cancer.
Ovarian cancer
Ovarian cancer develops much less frequently than breast cancer. Long-term estrogen monotherapy (for at least 5 to 10 years) was associated with a small increase in the risk of ovarian cancer. Some studies suggest that HRT with combination drugs has a similar or slightly lower risk. It is not known whether the risk of long-term use of low-potency estrogens (such as estriol) is different from that of monotherapy with other estrogens.
VTE
HRT is associated with an increase in the risk of developing VTE (deep vein thrombosis or pulmonary embolism) by 1.3-3 times. The likelihood of developing VTE is higher during the first year of HRT use than at a later date. In patients with a confirmed thrombophilic condition, the risk of VTE is high, and HRT may further increase this risk. Therefore, HRT is contraindicated in such women.
Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus, and cancer. There is no consensus regarding the possible role of varicose veins in the development of VTE. After any surgical intervention, VTE prophylaxis is necessary. In case of prolonged immobilization due to planned surgery, HRT should be temporarily discontinued 4-6 weeks before surgery and resumed only after the woman has regained full mobility.
In the absence of a woman's history of VTE, but in the presence of thrombosis at the age of less than 50 years in close relatives, it is recommended to conduct a screening examination, having previously discussed all its limitations (screening can only identify a number of thrombophilic disorders). If a disorder is detected that does not correspond to the disease in relatives, or if a “severe” defect is detected (for example, deficiency of antithrombin III, protein S or protein C, or a combination of these defects), HRT with estriol is contraindicated.
For women receiving long-term anticoagulant treatment, careful consideration of the benefit-risk profile of HRT is required.
If VET develops, therapy with Ovipol Clio should be discontinued immediately. A woman should be informed of the need to immediately consult a doctor if possible signs of thromboembolic complications appear (for example, swelling or tenderness along the vein of the lower extremity, sudden chest pain, shortness of breath, etc.).
IHD
There is no evidence from randomized controlled clinical trials that combined HRT or estrogen monotherapy can prevent myocardial infarction in women with and without coronary artery disease.
Estrogen monotherapy
According to randomized controlled clinical trials, in women with a history of hysterectomy, the risk of coronary artery disease is not increased with estrogen monotherapy. The absolute risk of coronary heart disease increases slightly with HRT with combined (estrogen + gestagen) drugs in patients over 60 years of age.
Ischemic stroke
HRT with combination drugs and estrogen monotherapy are associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with age and time after menopause. However, the baseline risk of stroke is more dependent on age, and the overall risk of ischemic stroke with HRT increases with age. The risk of hemorrhagic stroke does not increase with HRT.
Other states
Estrogens can cause fluid retention, and therefore patients with chronic heart and kidney failure should be under close medical supervision.
Estriol is a weak gonadotropin antagonist and has no other significant effects on the endocrine system.
It is necessary to monitor lipid levels in patients with pre-existing hypertriglyceridemia because, in rare cases, estrogen HRT has caused a significant increase in plasma triglyceride concentrations, leading to the development of pancreatitis.
Estrogens cause an increase in the concentration of thyroxine-binding globulin, which leads to an increase in total circulating thyroid hormone, measured as total protein-bound iodine; T4 (thyroxine) concentration or T3 (triiodothyronine) concentration.
The concentration of other plasma proteins (angiotensin-renin substrate, alpha-1-antitrypsin, ceruloplasmin) may also increase.
Cognitive function does not improve with HRT. There is evidence of an increased risk of developing dementia in women who start HRT with combination drugs or continuous estrogen monotherapy after 65 years.
Ovipol Clio contains cetyl alcohol and stearic alcohol, which can cause local skin reactions (for example, contact dermatitis).
