UK Clinical Pharmacy Association

Estradiol with levonorgestrel

Brands of this drug

FemSeven Conti, Nuvelle TS Phase II

Issues for surgery

Risk of menopausal symptoms, e.g. hot flushes, if discontinued pre-operatively.

Advice in the perioperative period

Elective surgery 

Continue (but ensure patch sited away from site of operation) – see Further information.

Emergency surgery

Continue (but ensure patch sited away from site of operation) – see Further information.

Patients admitted with gallstones (cholelithiasis)

Use of estradiol (with levonorgestrel) 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 estradiol.

Post-operative advice


Patients undergoing major gynaecological surgery

Review appropriateness of restarting this preparation after major gynaecological surgery.

Interactions with common anaesthetic agents


Administration of a single bolus dose of sugammadex is predicted to cause a 34% decrease in progestogen exposure. This predicted pharmacokinetic reaction has not been proven clinically, however bear the potential reaction in mind should breakthrough bleeding be reported after concomitant use.

Interactions with other common medicines used in the perioperative period


Since oestrogen metabolism can be affected by concomitant use of medicines that affect cytochrome p450 enzymes, specifically CYP3A4; the manufacturers note that use of an inducer 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 these medications and there is a change in therapeutic effect.

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.

Further information

Risk of VTE with transdermal HRT preparations containing oestrogen

Transdermal administration of oestrogen avoids first pass metabolism and thus has less effect on the coagulation factors than oral HRT. The risk associated with transdermal HRT given at standard therapeutic doses is no greater than the baseline population risk. Since transdermal 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.


Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. [Accessed on 5th January 2024]

Summary of Product Characteristics – FemSeven® (estradiol hemihydrate, levonorgestrel) Conti 50 micrograms/7 micrograms/24 hours, transdermal patch. Theramex UK Limited. Accessed via 05/01/24 [date of revision of the text January 2022]

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. [Accessed on 5th January 2024]

National Institute of Health and Clinical Excellence (2019). NG23 Menopause: diagnosis and management. [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 – Sugammadex 100mg/ml solution for injection. Amarox Limited. Accessed via 24/01/24 [date of revision of the text September 2023]