Proginova® is not used for contraception. If it is necessary to use contraception, non-hormonal methods should be used (with the exception of calendar and temperature methods).
If you suspect a pregnancy, you should stop taking the pills until the pregnancy is excluded (see "Pregnancy and lactation").
In the presence or deterioration of any of the following conditions or risk factors, before starting or continuing with Proginova®, the relationship between individual benefit and the risk of treatment should be assessed.
When prescribing Proginova® to women who have several risk factors for thrombosis or a high degree of severity of one of the risk factors, the possibility of mutual strengthening of the effect of risk factors and the drug on the development of thrombosis should be taken into account. In such cases, the total value of the available risk factors is increased. In the presence of high Proginova ® preparation is contraindicated.
- Venous thromboembolism
In a number of controlled randomized clinical, as well as epidemiological studies, an increased relative risk of venous thromboembolism (VTE) in the background of HRT, i.e. thrombosis of deep veins or thromboembolism of the pulmonary artery.
Therefore, when prescribing Proginova® to women with risk factors for VTE, the risk-benefit ratio should be carefully weighed and discussed with the patient.
Risk factors for VTE development include individual and family history (the presence of VTE in close relatives in a relatively youngage may indicate a genetic predisposition) and severe obesity. The risk of VTE also increases with age. The question of the possible role of varicose veins in the development of VTE remains controversial.
The risk of VTE may temporarily increase with prolonged immobilization, "large" planned and traumatological operations or massive trauma. Depending on the cause or duration of immobilization, the expediency of temporarily discontinuing Proginova® should be decided. Immediately discontinue treatment if there is or suspected thrombosis symptoms.
- Arterial thromboembolism
In two large clinical trials, a possible increase in the risk of coronary artery disease during the first year of admission and the absence of a positive effect on this risk during follow-up are sketched in women with a combination of conjugated estrogens and medroxyprogesterone acetate in a constant mode. In one major clinical study, using only EFE, a potential reduction in the incidence of coronary artery disease among women aged 50-59 years was found in the absence of a general positive effect among the population of the study.As a secondary result, in two large-scale clinical studies with the use of EFS as monotherapy or in combination with MPA, a 30-40% increase in the risk of developing ischemic stroke was found. Therefore, it is not known whether this increased risk extends to HRT preparations containing other types of estrogens and progestogens or to non-oral methods of use.
- Endometrial cancer
With prolonged monotherapy with estrogen, the risk of developing hyperplasia or endometrial cancer increases. Studies have confirmed that with the addition of gestagens, this risk is reduced.
- Mammary cancer
According to clinical and observational studies, an increase in the relative risk of breast cancer in women using HRT for several years has been found. This may be due to earlier diagnosis, the acceleration of growth of an already existing tumor in the background of HRT, or a combination of both.
The relative risk increases with the duration of estrogen monotherapy, but may be absent or decreased. This increase is comparable to the increased risk of breast cancer in women with a later onset of natural menopause, as well as obesity and alcohol abuse.The increased risk gradually decreases to the usual level during the first few years after discontinuation of HRT.
Assumptions regarding the increased risk of developing breast cancer are based on the results of more than 50 epidemiological studies.
Data on the prevalence of breast cancer beyond the breast are controversial.
In two large-scale, randomized trials with EFS in monotherapy or in combination with MPA, after approximately 6 years of HRT use, estimated risk values of 0.77 (95% confidence interval: 0.59-1.01) or 1.24 (95 % confidence interval: 1.01-1.54), respectively. It is not known whether this increased risk also extends to other products for HRT, which include the Proginova® preparation.
HRT increases the mammographic density of the mammary glands, which in some cases may have a negative impact on the radiographic detection of breast cancer.
- Ovarian Cancer
During the epidemiological study, there was a slight increase in the risk of ovarian cancer in women who use estrogen replacement therapy (EST) for a long time (more than 10 years). At the same time, a meta-analysis of 15 studies did not reveal an increased risk in the use of EST.However, these data are currently controversial.
- Liver tumors
Against the background of the use of sex hormones, which include and means for HRT, in rare cases, there were benign, and even less often, malignant liver tumors. In some cases, these tumors led to a life-threatening intra-abdominal bleeding. With pain in the upper abdomen, enlarged liver, or signs of intra-abdominal bleeding in differential diagnosis, the probability of a liver tumor should be taken into account.
- Cholelithiasis
It is known that estrogens increase the lithogenicity of bile. Some women in the treatment with estrogen are predisposed to the development of cholelithiasis.
- Dementia
There are limited data showing an increased likelihood of dementia risk in women starting hormone replacement therapy at the age of 65 and older. The risk can be reduced if the use of HRT is started in early menopause, as observed in studies. It is not known whether this applies to other preparations of HRT, which include Proginova®.
- Other states
Immediately stop treatment when migraine-like or frequent and unusually severe headaches occur, as well as when other symptoms appear - possible precursors of ischemic stroke.
The relationship between HRT and the development of clinically significant arterial hypertension has not been established. Women taking HRT have reported a slight increase in blood pressure, but a clinically significant increase is rare. However, in some cases, with the development of a clinically significant hypertension in the presence of HRT, the cancellation of Proginova® can be considered.
In case of mild violations of the liver function, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, it is necessary to observe the doctor, as well as periodic studies of liver function. With worsening of liver function, Proginova® should be discontinued.
In case of recurrence of cholestatic jaundice or cholestatic pruritus observed for the first time during pregnancy or previous treatment with sex steroid hormones, it is necessary to immediately stop taking Proginova®.
Special care is required for women with moderately elevated concentrations of triglycerides. In such cases, the use of HRT may cause a further increase in the concentration of triglycerides in the blood, which increases the risk of acute pancreatitis.
Although HRT can affect glucose resistance and glucose tolerance in peripheral insulin, there is usually no need to change the treatment regimen for diabetic patients with HRT. However, women with diabetes mellitus should be monitored when using Proginova®.
In some patients, HRT may cause unwanted estrogen stimulation, such as abnormal uterine bleeding. Frequent or persistent abnormal uterine bleeding against the background of treatment is an indication for endometrial research to eliminate organic disease.
Under the influence of estrogens, the myomatous nodes of the uterus can increase in size. In this case, treatment should be discontinued.
It is recommended to stop treatment with the development of recurrence of endometriosis with the use of Proginova ®.
If you suspect a prolactinoma before starting treatment, you should exclude this disease. In case of detection of prolactinoma, the patient should be under close medical supervision (including periodic evaluation of prolactin concentration).
In some cases, there may be a chloasma, especially in women with a history of pregnant women with chloasma. During HRT, women with a tendency to develop chloasma should avoid prolonged exposure to sunlight or ultraviolet radiation.
The following conditions may occur or worsen in the background of HRT. Although their relationship with HRT is not proven, women with these conditions should be under the supervision of a doctor when using Proginova®: epilepsy; benign breast diseases; bronchial asthma; migraine; porphyria; otosclerosis; systemic lupus erythematosus; chorea.
In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.
Additional Information
There is no data on the need for dose adjustment in women under 65 years of age. When using Proginova ® in women over 65 years of age, you should take into account the information provided in the section "Special instructions".
The use of Proginova ® in women with impaired hepatic function not studied.
The use of Proginova ® in women with impaired renal function not studied. The available data indicate that there is no need for dose adjustment in such patients.
Medical examination and counseling
Before starting or resuming the use of Proginova®, you should familiarize yourself with the patient's medical history and perform a physical and gynecological examination. The frequency and nature of such surveys should be based on existing standards of medical practice, taking into account the individual characteristics of each patient (but not less than once in 6 months) and should include measurement of blood pressure, assessment of the mammary glands, abdominal organs and pelvic organs, including cytological examination of the epithelium of the cervix.
Influence on the results of laboratory studies
Admission of sex hormones can affect the biochemical parameters of the liver, thyroid, adrenal and kidney function,on the plasma content of transport proteins, such as corticosteroid-binding globulin, lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis.