Evorel Sequi

There is no image.

Method of action: Endocrine Therapy, Estrogen-Progestational, Sex Hormones And Modulators Of The Genital System

Treatment option: Hormone Replacement Therapy, Osteoporosis, Prevention Of Osteoporosis

Medically reviewed

Last updated on 10/01/2026

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Evorel Sequi

Quick Facts

Property	Description
Active ingredients	Estradiol and Norethisterone
Form	Transdermal patch (or system)
Pharmacological class	Estrogen-Progestogen Combination Therapy
Target Audience	Postmenopausal women with an intact uterus
Type	Sequential (Biphasic) HRT

Defining Evorel Sequi: A Combined HRT System

Evorel Sequi is a Prescription-only medicine (POM) categorized as a Combined Hormone Replacement Therapy (HRT). It belongs to the pharmacological class of Estrogen-Progestogen Combination Therapy, used to provide systemic replacement of hormones that naturally decline after menopause. This classification is clinically recognized for addressing the hormonal needs of postmenopausal women who retain an intact uterus, distinguishing it from Estrogen-only HRT. Its overarching purpose is to alleviate symptoms associated with the climacteric syndrome by restoring a more stable hormonal environment.

Composition and Delivery: The Transdermal Patch and Sequential Hormones

The preparation’s efficacy is based on two primary active ingredients, which are synthetic steroid hormones (derived): Estradiol (the key estrogen component) and Norethisterone (the progestogen component). The unique dosage form is a Transdermal patch or system, designed for Systemic absorption via the Transdermal route. This form offers sustained hormone release, a feature supported by decades of regulatory oversight. Furthermore, the preparation is organized as a Sequential regimen (or Biphasic regimen), meaning it provides continuous Estradiol alongside cyclical Norethisterone. This specific sequential structure is the defining feature that differentiates it from continuous combined HRT systems.

General Purpose of Evorel Sequi

The fundamental general purpose of this medication is Hormone Restoration, aiming to compensate for the significant deficiency of natural Estrogen in the body to control related deficiency symptoms. While the Estradiol provides the necessary Estrogenic effect, the inclusion of Norethisterone is critical for Endometrial protection. This cyclical Progestogenic effect ensures that the uterine lining undergoes periodic Endometrial shedding, a necessary physiological action that balances the hormonal action and maintains the safety profile for women with an intact uterus.

What side effects are possible with Evorel Sequi?

Possible Side Effects and Safety Information

The safety profile of Evorel Sequi, a sequential combined Hormone Replacement Therapy (HRT), is categorized by regulatory bodies based on documented adverse reactions and physiological impact. The inclusion of the progestogen component, Norethisterone, is a key safety measure required to protect the endometrium against the increased risk of hyperplasia and cancer associated with unopposed estrogen therapy in individuals with an intact uterus.

Documented Frequencies and Systemic Risks

Adverse reactions are classified by frequency as reported in clinical data:

Very Common: Skin reactions at the application site, such as irritation, redness, or itching, are the most frequently reported effects due to the transdermal delivery system.
Common: Effects reported to affect up to 1 in 10 users include Headache, Breast pain or tenderness, Nausea, Abdominal pain, Mood changes, Weight gain, Fluid retention (Oedema), and Irregular vaginal bleeding or spotting.

Adverse reactions such as irregular bleeding are often more common at the initiation of treatment and may diminish over the first few months. Conversely, the risk of certain serious systemic adverse reactions is linked to the duration of use.

Serious Adverse Reactions

The regulatory documentation for systemic combined HRT identifies specific serious risks that include an increased incidence of Venous Thromboembolism (VTE), Arterial Thromboembolic Events (e.g., stroke and myocardial infarction), and Breast Cancer. Use is typically restricted in individuals with a history of thromboembolic disease, active hepatic impairment, or undiagnosed abnormal uterine bleeding. Furthermore, the risk of Probable Dementia has been noted in studies involving older women (aged 65 years and over) receiving estrogen plus progestogen.

Overdose and Emergency Response

Overdose and When to Seek Help

This section outlines the official, regulatorily documented information regarding an overdose of Evorel Sequi (estradiol and norethisterone acetate transdermal patches), strictly based on governmental health authority sources.

Documented Overdose Manifestations

Symptoms of overdose, which can occur with overexposure to estrogen and progestogen, are generally not life-threatening and are managed symptomatically. The official regulatory documents cite the following manifestations:

Nausea and vomiting.
Withdrawal bleeding (vaginal bleeding) in women.

Immediate Actions and Management

In the event of a suspected or confirmed overdose, the regulatory labeling provides guidance on the required management:

Management Action	Regulatory Guidance
Antidote Information	No specific antidote is available.
Supportive Measures	Any overdosage should be treated symptomatically.
Emergency Attention	Seek immediate medical attention or contact a poison control center if symptoms are severe or persistent, or if a significant overexposure is suspected.

Overdosage management focuses entirely on supportive care and the relief of symptoms (symptomatic treatment). The nature of transdermal administration generally limits the potential for extreme acute overdosage compared to oral formulations, with the primary clinical presentations centered on the gastrointestinal and reproductive systems.

Therapeutic Uses of Evorel Sequi

Evorel Sequi is clinically applied as a sequential Combined Hormone Replacement Therapy (HRT). It provides support that helps ease the overall symptom burden from conditions driven by postmenopausal oestrogen deficiency. Its therapeutic utility is commonly used in situations involving certain distressing symptoms.

Key Therapeutic Focus and Benefits

This therapy is relevant for managing conditions characterized by periods of heightened symptoms. This includes symptoms related to systemic imbalance, such as frequent hot flushes and disruptive night sweats, alongside urogenital atrophy (e.g., vaginal dryness) and psychological manifestations (e.g., mood swings). It is also commonly used to help manage postmenopausal osteoporosis in women at high risk of future fractures. The therapy is commonly used in settings where additional management of discomfort is required.

Symptom Support and Clinical Context

This regimen is generally used to help address symptoms related to heightened physiological activity and those that may become intense or disruptive. The supportive relief may assist with more consistent sleep patterns and coping more steadily with symptom fluctuations. This context is relevant when supportive symptom management is appropriate and contributes to easing the overall symptom load.

Quick Fact: Support for Symptom Management
Applied across domains where additional symptomatic support is needed.
Relevant for easing symptoms that interfere with daily functioning.
Supports general well-being during symptomatic phases.

Eligibility and Restrictions for Use

Who Can and Cannot Use Evorel Sequi?

This section describes population eligibility rules for Evorel Sequi based strictly on official regulatory labeling. Use is primarily established for postmenopausal women who retain an intact uterus.

Absolute Contraindications

The medicine is absolutely contraindicated (must not be used) in women with a history of, active, or suspected breast cancer or other oestrogen-dependent malignant tumours, or with untreated endometrial hyperplasia.

Use is also forbidden in those with previous or current venous or arterial thromboembolic disease (e.g., deep vein thrombosis, stroke, heart attack), active liver disease, or certain thrombophilic conditions.

Eligibility Restrictions

Population Status	Regulatory Rule
Pregnancy/Lactation	Contraindicated in both pregnancy and breastfeeding.
Pediatric Use	Not for use in children or adolescents.
Geriatric Use	Experience in women over 65 years is limited; data is insufficient.
Conditional Use	Requires close medical supervision for conditions such as hypertension, uterine fibroids, liver disorders, and severe migraine.
Organ Impairment	Data is insufficient to guide dose adjustments for patients with severe liver or kidney function impairment.

What should I know about interactions with other medicines?

Interactions with other medicines and products

Certain medicinal products can influence the concentration and effectiveness of the hormones in Evorel Sequi. This interaction generally involves the induction of liver enzymes, predominantly Cytochrome P450 3A4 (CYP3A4), which can accelerate the metabolism of the estradiol and norethisterone.

Medicines that may reduce Evorel Sequi's effect

Medicines identified in official sources that may potentially reduce the therapeutic effect include, but are not limited to, products used for:

Epilepsy: Certain anticonvulsant medicines.
Tuberculosis: Rifampicin and other medicines for tuberculosis.
HIV/Hepatitis C: Certain antiviral agents (e.g., Dasabuvir, Ombitasvir, Paritaprevir, Ritonavir).
Antibiotics: Some antibiotics may affect hormone levels.
Herbal Products: Preparations containing St. John's wort (Hypericum perforatum).

Procedural constraint

Creams, lotions, or powders applied to the skin area where the patch is placed should be avoided. These topical products may interfere with the adhesive properties of the patch, potentially compromising the absorption of the active ingredients.

Mechanism of Action

Evorel Sequi delivers a sequential transdermal administration of 17beta-estradiol and norethisterone acetate. Estradiol, the estrogenic component, is a selective agonist of nuclear estrogen receptors (ERs), primarily ER alpha and ER beta, located in target tissues such as bone, brain, and the reproductive tract. Upon binding, the estradiol-ER complex translocates to the nucleus, dimerizes, and interacts with estrogen response elements (EREs) on the DNA promoter regions, modulating the transcription of specific genes. This action modifies the synthesis of various proteins, enzymes, and co-regulators.

Norethisterone, a progestogen, functions as an agonist of the nuclear progesterone receptor (PR). The activated progestogen-PR complex also binds to its cognate DNA sequences, progesterone response elements (PREs), inducing transcription factors that alter gene expression. In the sequential regimen, the progestogen component selectively counteracts the proliferative transcriptional effects induced by the estrogen component on the endometrial cells, resulting in a cyclical shedding of the uterine lining. The systemic consequences involve the modulation of regulatory feedback loops within the hypothalamic-pituitary-ovarian axis and the regulation of cellular function in estrogen- and progesterone-responsive tissues.

Dosage and Administration Information

How to Use Evorel Sequi

Evorel Sequi is a prescription medication administered exclusively via the transdermal route as part of a continuous, sequential combined hormone replacement therapy (HRT) regimen. The entire therapeutic course is structured into repeated 28-day cycles and utilizes two different types of patches within this period to deliver hormones systemically through the skin.

Dosing Schedule and Frequency

The standard adult regimen involves applying a new patch twice weekly, with each patch worn for three to four days. This frequency is necessary to ensure stable delivery of the active ingredients, which include 50 mu g estradiol/24 hours and 170 mu g norethisterone acetate/24 hours when using the combined phase patch. The sequential delivery pattern is mandatory:

Cycle Phase	Duration	Patch Type and Hormone Delivery
Phase 1	First 14 days	Estradiol-only (Evorel 50)
Phase 2	Next 14 days	Estradiol and Norethisterone (Evorel Conti)

Administration and Procedural Rules

Application of the patch must be to clean, dry, intact skin below the waistline, such as the hips or buttocks. A key procedural rule requires the rotation of the application site; a new patch must be placed on a different area of skin, ensuring at least seven days pass before reapplying to the same spot. The patch should not be applied to the breasts. If a patch is inadvertently removed or falls off, it must be replaced immediately with a new patch of the same type, but the patient must adhere to the original designated change days for all subsequent patches to preserve the planned sequential pattern.

Recent Clinical Evidence

Research Evidence / Overview of Studies for Evorel Sequi

Evidence for Oestrogen Deficiency Symptoms

Research was studied in research related to oestrogen deficiency symptoms, such as hot flashes and night sweats. Study designs included randomized controlled trials (RCTs), systematic reviews, and long-term observational cohort studies which are relevant in trials assessing short-term or episodic symptom patterns. These studies research examined a variety of outcomes related to physical discomfort. Outcomes monitored included specific quality of life (QoL) measures in postmenopausal women.

Studies data show patterns related to measured outcomes in populations observed when the estrogen component was used. Trials studies report how symptoms evolved in the observed populations, including patterns in the recording of vasomotor symptom frequency and severity. This evidence contributes to understanding symptom patterns related to conditions characterized by fluctuating or episodic manifestations.

Evidence for Prevention of Postmenopausal Osteoporosis

The combined HRT class was studied for outcomes related to systemic or functional imbalance in bone density. Study designs primarily consisted of controlled clinical trials, including RCTs, which studies explored outcomes related to systemic or functional imbalance in bone density. These trials research examined changes in Bone Mineral Density (BMD) at critical sites like the hip and spine, and longer-term observational follow-up studies monitored fracture incidence.

Findings describe patterns observed in the studies regarding BMD measurements. These data show patterns related to mineral content in the bone structure in the observed groups.

What is Still Uncertain About the Research Landscape

The evidence landscape, while mature in many areas, still contains gaps. Evidence is limited and data are still emerging in certain comparative contexts. Comparative evidence is lacking between this specific transdermal sequential patch and all other available HRT formulations. Findings were mixed or subgroup findings are uncertain regarding specific outcomes in certain populations, like women over 65, where results apply only to the populations studied in the original trials. Overall, while studies help show what has been observed so far for the core indications, comparative evidence is lacking where specific, long-term, product-unique controlled data is concerned.

Key Studies & References

Menopause: diagnosis and management (NICE Guideline NG23)

Frequently Asked Questions (FAQ)

Common questions about Evorel Sequi (FAQ)

Q: Why is this specific patch called 'Sequi'?

The term "Sequi" refers to the sequential regimen of the medication. This means the treatment cycle uses two different types of patches within a 28-day period. This sequential approach is designed to provide estrogen continuously while adding progestogen cyclically.

Q: How quickly should I expect to notice any difference after starting the patches?

Official product information suggests that improvements in menopausal symptoms are reported within a few weeks of beginning treatment. However, it is stated that it may take up to three months for the body to adjust and for the full effects to be observed.

Q: Can the heat from a sauna or intense exercise affect the patch's delivery?

The official product information indicates that the patch is required to be removed prior to a sauna bath. If the patch is removed for a sauna, a new patch is required to be applied immediately afterward. It is not necessary to remove the patch for routine bathing or showering.

Q: What happens if I forget to change my Evorel Sequi patch exactly on time?

Regulatory guidance indicates that if a patch change is missed, it should be replaced as soon as the individual remembers. After replacing the patch, the user is required to continue following their original designated patch change days. Missing a change day may increase the likelihood of breakthrough bleeding or spotting.

Q: Are there any warnings about surgery and using the Evorel Sequi patch?

Transdermal HRT, such as this patch, is generally not required to be discontinued before elective surgery. This is because the transdermal route is not associated with the same increased risk of venous thromboembolism (VTE) as oral hormone therapy. If surgery is planned, the patch should be located away from the operation site.

Q: Can Evorel Sequi be used if I have a history of migraines?

Official documents indicate that individuals with a history of migraine or severe headache are listed as conditions that require close medical supervision. This is because these conditions may recur or be aggravated while undergoing hormone replacement therapy.

Q: Can the Evorel Sequi patch cause changes in sleep patterns?

According to the official product information, being unable to sleep (insomnia) is listed as a common side effect. This means it has been reported to affect up to 1 in 10 users.

Q: I heard that Evorel Sequi might interact with certain supplements; is that true?

The product information lists specific interactions with certain preparations. Notably, herbal preparations containing St. John's Wort may reduce the effect of the hormones in the patch. This is due to the way these herbal components can affect the enzymes that break down the hormones in the body.

Q: Can I use Evorel Sequi if I am a smoker?

Official warnings note that smoking is a known risk factor for serious systemic adverse reactions. These serious risks, such as venous thromboembolism (VTE), are associated with systemic HRT use.

Q: What is the duration of treatment generally recommended by medical guidelines?

Regulatory documents related to the treatment of menopausal symptoms state a general principle for use. For both initiation and continuation, the recommendation is to use the lowest effective dose for the shortest duration necessary.

Q: Is there a maximum age limit for starting or continuing treatment with this patch?

The official product information states that experience in women older than 65 years is limited. Therefore, data is insufficient to fully guide the use or to set a specific maximum age limit for this age group.

Q: Is it possible to become pregnant while using Evorel Sequi for menopausal symptoms?

Evorel Sequi is not classified as a contraceptive and does not provide protection against pregnancy. If a woman is under 50 years old or it has been less than 12 months since her last menstrual period, additional non-hormonal contraception may be required.

Q: Can Evorel Sequi affect cholesterol levels?

The product information warns that use in individuals with pre-existing hypertriglyceridaemia requires careful observation. Studies have reported that in rare cases, oestrogen therapy can cause large increases in plasma triglycerides for this specific population.

Q: What are the non-hormonal ingredients used in the patch adhesive?

The transdermal patch system contains non-hormonal components in its adhesive film. The official product documentation lists the patch adhesive film as composed of acrylic adhesive and guar gum.

Q: Does this patch contain any synthetic progesterone?

Yes, the patch contains a progestogen component to protect the uterine lining. This ingredient is norethisterone acetate, which is described in official product information as a synthetic form of progestogen.

Q: Can people with a history of liver issues use Evorel Sequi?

According to the contraindications, active liver disease is an absolute reason why the medication cannot be used. A history of liver disease is also a contraindication if the individual's liver function tests have failed to return to normal.

Q: Can Evorel Sequi cause stomach or digestive issues?

Official documentation lists several digestive side effects that are considered common. These common effects include nausea (feeling sick), abdominal pain, wind, other stomach upsets, and diarrhoea.

Q: Are there specific instructions for disposing of the used patches?

Regulatory instructions state that used patches are required to be folded in half so the adhesive sides stick together before disposal. It is explicitly required that used patches must not be flushed down the toilet, and they should be kept out of the sight and reach of children and pets.

How should Evorel Sequi be stored and disposed of?

How to Store and Dispose of Evorel Sequi: Official Regulatory Requirements

Storage and disposal of Evorel Sequi transdermal patches must strictly follow the conditions mandated by regulatory labeling.

Storage Conditions

Evorel Sequi must be stored at a temperature below 25 C (not above 25 C) and protected from moisture and light. It is required to keep the patches in their original sachet and outer carton until use and they must not be frozen or refrigerated. The product must be kept out of the sight and reach of children and pets at all times.

Disposal Instructions

Do not use the patches after the labeled expiry date. Used patches should be folded in half with the adhesive sides together and disposed of in household waste. It is explicitly required not to flush used patches down the toilet. Unused or expired medicines should be returned to a pharmacy for safe disposal.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.