Oekolp forte: composition and pharmaceutical form
One pessary contains 0.5 mg of estriol. It is a vaginal suppository and is inserted into the vagina before going to bed at night. To take the pessary out of the pack, the aluminium foil is torn from the tip along the pessary, following the arrow, until the pessary can be removed easily.
The composition includes butylated hydroxytoluene, which may cause a local skin reaction — for example contact dermatitis — or irritation of the eyes and mucous membranes. It is separately stated that the medicine is not intended for use as a contraceptive and that it has no influence on the ability to drive or to operate machinery.
How Oekolp forte works
Estriol is the main metabolite of estradiol and estrone and is produced mainly in the liver. Unlike other oestrogens, it binds weakly to the specific receptors of oestrogen-sensitive target organs; once inside the cell nucleus it induces the synthesis of particular proteins. Estriol allows the epithelium of the vulva to return physiologically to normal and promotes proliferation of the mucosal layers of the vagina, cervix, urethra and bladder by increasing vascularisation and blood flow. Atrophy and functional disturbances of these organs caused by oestrogen deficiency — for example after removal of the ovaries or during the postmenopausal period — are for the most part reversed by oral or vaginal administration of estriol. For the treatment of osteoporosis and arteriosclerosis estriol is not suitable.
The effect on the vaginal mucosa secondarily increases glycogen storage and colonisation by Döderlein bacilli and normalises pH, while mucus secretion increases. At the same time estriol given vaginally in therapeutic doses has no significant effect on the endometrium: even at higher doses it produces no proliferative action, or only a weak one, and as a consequence the likelihood of an adverse reaction such as bleeding is very low. Estriol does not affect other hormones or hepatic metabolism, so the usual therapeutic dose does not change protein synthesis, lipid metabolism or blood clotting.
Indications
The medicine is used within hormone replacement therapy and is prescribed for three reasons, of which only the first is treatment proper.
The indications are worded as follows.
- hormone replacement therapy for atrophic changes of the lower genitourinary tract caused by oestrogen deficiency;
- pre- and postoperative treatment of postmenopausal women undergoing vaginal procedures;
- as a diagnostic aid in the case of an equivocal cytological picture of a cervical smear — that is, so that the repeat smear is informative.
Method of use and dosage
Usually one pessary a day is used, and this dose should not be exceeded. It is inserted vaginally before sleep. To start and to continue treatment of postmenopausal symptoms the lowest effective doses are used for the shortest possible time, and the benefit-risk ratio of replacement therapy is assessed at least once a year.
| Situation | Regimen |
| Atrophic changes of the lower genitourinary tract | 1 pessary once a day for about 3 weeks; after that a maintenance dose of 1–2 pessaries a week is usually effective |
| Before a vaginal procedure | 1 pessary a day for the 2 weeks before the operation |
| After a vaginal procedure | 1 pessary twice a week for the 2 weeks after the operation |
| Preparation for a repeat smear | 1 pessary every other day during the week preceding the next smear |
| Missed dose | use it as soon as possible; if the omission is noticed on the day of the next dose, the missed one is skipped and the previous schedule continued — two doses are never used in one day |
| Switching from another replacement therapy | women not on it, or wishing to replace continuous combined therapy, may start at any time; on continuous sequential therapy they start a week after the end of the cycle |
Before treatment is started or resumed, a detailed medical history including the family history is taken, and the physical examination — covering the pelvis and the breasts — is based on that history, on the contraindications and on the precautions. During treatment follow-up visits are recommended, with a frequency and character matched to the individual patient, and investigations including mammography are carried out in line with current screening practice. The woman is told which changes in the breasts she should report to her doctor.
Contraindications
Hypersensitivity to estriol or to any excipient; current or past breast cancer, or suspicion of it; oestrogen-dependent malignant tumours present now or suspected, for example endometrial cancer; genital bleeding of unknown origin; untreated endometrial hyperplasia.
The second half of the list concerns the vessels and the liver.
- deep vein thrombosis or pulmonary embolism now or at any earlier time;
- known clotting disorders, for example protein C, protein S or antithrombin deficiency;
- any arterial thromboembolic disorder experienced at any time — angina, myocardial infarction;
- active liver disease, and disease suffered earlier, until liver function tests return to normal values;
- porphyria.
Special warnings and precautions
Replacement therapy for menopausal symptoms is used only when those symptoms adversely affect quality of life, and it is continued exactly as long as the benefit outweighs the risk. There is little data on the risks of such therapy in premature menopause, but because the absolute risk in younger women is low, the benefit-risk ratio may be more favourable for them than for older women.
- women remain under continuous supervision if they have now, have had in the past, or saw worsen during pregnancy or previous hormonal treatment: uterine leiomyoma or endometriosis, risk factors for thromboembolic disorders, risk factors for oestrogen-dependent tumours such as breast cancer in first-degree relatives, hypertension, liver disease, diabetes, gallstones, migraine or severe headache, systemic lupus erythematosus, a history of endometrial hyperplasia, epilepsy, asthma, otosclerosis — during treatment these conditions may recur or worsen;
- treatment is stopped if any contraindication appears, and also in cases of jaundice or impaired liver function, a marked rise in blood pressure, new-onset migraine-type headache, and pregnancy;
- if surgery followed by prolonged immobilisation is planned, temporary interruption of therapy 4–6 weeks before the operation is recommended, with resumption only after the patient is fully mobile; and if the medicine has been prescribed precisely as pre- and postoperative preparation, prophylactic anticoagulant treatment is considered;
- replacement therapy is associated with a 1.3- to 3-fold increase in the risk of venous thromboembolic disease, and such episodes are more likely in the first year of treatment than later; those studies did not concern this medicine and there is no data on whether it carries the same risk;
- combined oestrogen-progestogen therapy and oestrogen therapy increase the risk of ischaemic stroke by up to half as much again; the relative risk changes neither with age nor with the time since menopause, but since the baseline risk of stroke is strongly age-related, the total risk grows over the years; randomised trials have not shown protection against myocardial infarction;
- ovarian cancer is far less common than breast cancer; according to a large meta-analysis the risk is slightly increased, becomes apparent over 5 years of use and decreases with time after withdrawal;
- oestrogens may cause fluid retention, so patients with heart or kidney failure need close monitoring; replacement therapy does not improve cognitive function, and for women who start it after the age of 65 there is some evidence of an increased risk of probable dementia.
The breast deserves separate mention. Replacement therapy, especially combined oestrogen-progestogen therapy, increases the radiological density of breast tissue on mammography, which may make cancer harder to detect. Clinical studies have shown that, unlike the other oestrogens, estriol does not increase the density of glandular breast tissue on mammography, and an epidemiological study of 3345 women with advanced breast cancer and 3454 healthy women found no link between estriol and an increased risk of that cancer — a link that was established for other oestrogens. The clinical significance of these findings is not yet confirmed, so before starting therapy its benefit and the risk of breast cancer are weighed against each other.
Interactions with other medicines
In clinical practice no interactions of the medicine with other medicinal products have been established. The data, however, are limited and interactions are possible: those described for combined oral contraceptives may apply to this medicine as well.
The metabolism of oestrogens may be enhanced by concomitant use of substances known as inducers of the enzymes responsible for the medicine's metabolism, above all inducers of cytochrome P-450 enzymes. These include antiepileptic medicines such as phenobarbital, phenytoin and carbamazepine, and medicines used to treat infections: rifampicin, rifabutin, nevirapine, efavirenz. Ritonavir and nelfinavir are known as inhibitors which, when given together with steroidal anti-inflammatory drugs, display strong inducing properties. Preparations containing St John's wort can also stimulate oestrogen metabolism. Clinically, increased metabolism of oestrogens may weaken the medicine's effect and change the pattern of uterine bleeding.
Pregnancy and breastfeeding
The medicine is intended solely for the treatment of postmenopausal women — whether the menopause occurred naturally or followed surgery. In pregnancy it is contraindicated: if the patient becomes pregnant during treatment, treatment must be stopped immediately.
The results of epidemiological studies relating to inadvertent exposure of the fetus to oestrogens have shown no teratogenic or toxic effect. During lactation the medicine is not indicated: estriol is excreted in human milk and may reduce its quantity.
Adverse reactions
The reactions listed come from a review of the literature and from reports received after the medicine was placed on the market. They are usually transient, but they may also indicate too high a dose.
- metabolism and nutrition disorders: fluid retention in the body;
- gastrointestinal disorders: nausea;
- reproductive system and breast disorders: breast discomfort and pain, postmenopausal genital spotting, cervical discharge;
- general disorders and administration site conditions: irritation at the site of administration and itching, flu-like symptoms.
A separate list covers reactions reported with oestrogen-progestogen therapy: oestrogen-dependent benign and malignant tumours, for example endometrial cancer; myocardial infarction and stroke; inflammation of the gallbladder; subcutaneous and skin disorders — chloasma, erythema multiforme, erythema nodosum, vascular purpura; probable dementia above the age of 65. The risk of breast cancer in women on combined oestrogen-progestogen therapy for longer than 5 years is raised as much as twofold; with oestrogen-only therapy the increase in risk is significantly lower, and the level of risk depends on the duration of therapy.
Overdose
The acute toxicity of estriol in animals is very low, so overdose of the medicine given vaginally is unlikely.
If a large amount of estriol is swallowed, nausea, vomiting and bleeding may occur. There is no specific antidote; symptomatic treatment is used if needed.
How to get an Oekolp forte prescription online
The medicine is available on prescription, and the conversation with the doctor is built around what it is prescribed for: atrophic changes of the lower genitourinary tract, preparation for a vaginal operation and recovery afterwards, or preparation for a repeat cytological smear. The doctor is told whether the menopause came naturally or after surgery, and how long ago.
For the online consultation it is worth preparing the information that decides whether replacement therapy is permissible: past or current breast cancer and oestrogen-dependent tumours, genital bleeding of unclear origin, thromboses and embolisms in the patient and in close relatives, clotting disorders, angina and infarction, liver disease and porphyria. Hypertension, diabetes, migraine, epilepsy, asthma, fibroids and endometriosis are also mentioned, along with the date of the last mammogram and the medicines being taken, especially antiepileptics, anti-infectives and St John's wort. The doctor will assess these circumstances and, if there are no contraindications, will issue an electronic prescription.
