Brands of this drug
Tablet: Elleste Solo, Progynova, Zumenon
Transdermal Patch: Elleste Solo MX, Estraderm MX, Estradot, Evorel, Femseven, Nuvelle TS Phase 1, Progynova TS,
Transdermal Gel: Oestrogel, Sandrena
Transdermal Spray: Lenzetto
Vaginal Preparations: Estring, Vagifem, Vagirux
Issues for surgery
Risk of menopausal symptoms, e.g. hot flushes, if discontinued pre-operatively.
Reduced protection against osteoporosis if discontinued for prolonged period.
For oral preparations only - risk of venous thromboembolism (VTE) if continued.
Advice in the perioperative period
Elective surgery
Minor surgery
Continue unless there is a risk of prolonged immobilisation – see Major surgery.
Ensure adequate VTE prophylaxis if oral preparations continued.
Major surgery
Oral preparations: consider stopping 4-6 weeks before major elective surgery where prolonged immobilisation is likely, particularly vascular and orthopaedic lower limb surgery. See Further information.
Consider other risk factors that the patient may have that further increase the risk of VTE, e.g. age, weight, previous history of VTE.
If stopping pre-operatively, consider switching transdermal HRT
Please note, if doses are missed, it may result in breakthrough bleeding in women with a uterus.
Transdermal preparations: continue (but ensure patch sited away from site of operation) – see Further information.
Vaginal preparations: continue (unless undergoing gynaecological procedure and advised otherwise by surgeon) – see Further information.
Emergency surgery
Oral preparations: ensure adequate thromboprophylaxis to reduce risk of VTE.
If prolonged immobilisation anticipated, consider discontinuing on admission.
Please note, if doses are missed, it may result in breakthrough bleeding in women with a uterus.
Transdermal preparations: continue (but ensure patch sited away from site of operation) – see Further information.
Vaginal preparations: continue – see Further information.
Patients admitted with gallstones (cholelithiasis)
Use of estradiol can aggravate gallstones in patients who have a previous history of this condition; bear this in mind for patients admitted with gallstones who are on this medication.
Post-operative advice
If oral preparations are stopped pre-operatively restart after full mobilisation.
Patients undergoing major gynaecological surgery
Review appropriateness of restarting this preparation after major gynaecological surgery.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
Dexamethasone
Since oestrogen metabolism can be affected by concomitant use of medicines that affect cytochrome P450 enzymes, specifically CYP3A4; the manufacturer’s note that concomitant use of inducers of CYP3A4, such as dexamethasone, may reduce plasma concentrations of oestrogen, with a possible reduction in therapeutic effect and/or changes in uterine bleeding. It is unlikely that use of dexamethasone perioperatively will have a significant effect, but bear the interaction in mind where, there is concomitant use of both medications and there is a change in therapeutic effect.
Antimicrobials
Since oestrogen metabolism can be affected by concomitant use of medicines that affect cytochrome P450 enzymes, specifically CYP3A4; the manufacturer’s note that concomitant use of medicines that inhibit CYP3A4, such as erythromycin/clarithromycin, may increase plasma concentrations of oestrogen, with a possible increase in side-effects. Whilst single surgical prophylactic doses should not pose a problem, bear the interaction in mind where a course is required, estradiol has been continued pre-operatively and the patient experiences an increase in side-effects.
With transdermal HRT administration, the first-pass effect in the liver is avoided and, thus transdermally applied oestrogens HRT may be less affected than oral preparations by enzyme inducers/inhibitors.
There is minimal systemic absorption with vaginal administration hence, it is unlikely that any clinically relevant drug interactions will occur with vaginal HRT preparations.
Further information
Risk of VTE with oral HRT preparations containing oestrogen
During first pass metabolism in the liver oral HRT preparations containing oestrogen affect the clotting cascade by increasing resistance to protein S and protein C (natural anticoagulants) and increasing fibrinogen, thus increasing the risk of thrombosis. Patients taking oral HRT are at increased risk of VTE compared with non-users. The risk is thought to be greatest in the first year of treatment and also in women with an increased body mass index. The baseline risk of VTE also increases substantially with age.
The risk of VTE varies depending on the oestrogen (and progesterone) content of the preparation. Preparations with conjugated equine oestrogen are associated with higher VTE risk compared to those with estradiol. Higher doses of oestrogen are also associated with higher VTE risk. The highest risk is with preparations containing both conjugated equine oestrogen and medroxyprogesterone acetate and the lowest risk is with estradiol with dydrogesterone.
Risk of VTE with transdermal/vaginal HRT preparations containing oestrogen
Transdermal/vaginal administration of oestrogen avoids first pass metabolism and thus has less effect on coagulation factors than oral HRT. The risk associated with transdermal/vaginal HRT given at standard therapeutic doses is no greater than the baseline population risk. Since transdermal/vaginal HRT has little or no impact on coagulation and is not associated with an increased risk of VTE it does not need to be discontinued before elective surgery.
References
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 5th January 2024]
Summary of Product Characteristics – Elleste (estradiol) Solo® 2mg Tablets. Mylan. Accessed via www.medicines.org.uk 05/01/24 [date of revision of the text August 2023]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 5th January 2024]
National Institute of Health and Clinical Excellence (2019). NG23 Menopause: diagnosis and management. https://www.nice.org.uk/guidance/ng23 [Accessed on 5th January 2024]
Vinogradova, Y. Coupland, C & Hippisley-Cox, J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019; 364: k4810. DOI: 10.1136/bmj.k4810
Summary of Product Characteristics – Estraderm (estradiol hemihydrate) MX 100. Merus Labs Luxco II S.à R.L. Accessed via www.medicines.org.uk 21/01/24 [date of revision of the text July 2023]
Summary of Product Characteristics – Sandrena (estradiol hemihydrate) 1.0mg gel. Orion Pharma (UK) Limited. Accessed via www.medicines.org.uk 21/01/24 [date of revision of the text July 2022]
Summary of Product Characteristics – Lenzetto® (estradiol hemihydrate) 1.53 mg/spray, transdermal spray, solution. Gedeon Richter (UK) Ltd. Accessed via www.medicines.org.uk 21/01/24 [date of revision of the text September 2022]
Summary of Product Characteristics – Vagifem® (estradiol hemihydrate) 10 micrograms vaginal tablets. Novo Nordisk Limited. Accessed via www.medicines.org.uk 21/01/24 [date of revision of the text July 2022]