Novofem

Novofem is a sequential combined hormone replacement therapy (HRT) containing both oestrogen and progestogen. Each calendar pack contains 16 white tablets each containing estradiol 2 mg (the oestrogen phase) followed by 12 red tablets each containing estradiol 2 mg plus norethisterone acetate 1 mg (the combined phase). Novofem is manufactured by Novo Nordisk and is taken on a continuous daily basis, producing a monthly withdrawal bleed at the end of each cycle.

Who Novofem Is For

Novofem is indicated for the treatment of menopausal symptoms in women who have not had a hysterectomy (i.e., women who still have a uterus). It is specifically designed for perimenopausal women or those within 12 months of their last natural period. Sequential HRT - in which progestogen is added for only part of the monthly cycle - is preferred in early menopause because it better mimics the natural hormonal fluctuation of the premenopausal cycle and produces predictable monthly bleeds.

Women who are more than 12 months past their last period (post-menopausal) are generally better suited to continuous combined HRT preparations (where oestrogen and progestogen are taken simultaneously every day), as these aim to avoid monthly bleeds altogether. If a woman is taking Novofem and their withdrawal bleeds become very irregular or persistent, their prescriber may need to reassess the appropriateness of sequential HRT.

Benefits of HRT

Novofem effectively relieves the common symptoms of the menopause, including hot flushes, night sweats, vaginal dryness, sleep disturbance, and mood changes. It also helps to maintain bone density, reducing the long-term risk of osteoporotic fractures. These benefits are balanced against the known risks of HRT, particularly in relation to breast cancer risk with prolonged use, which should be discussed with each patient individually.

How to Take Novofem

Take one Novofem tablet each day following the sequential order of the pack, swallowed whole with water at the same time each day. The 28-day pack has two phases: 16 days of oestrogen-only (white tablets) followed by 12 days of combined oestrogen and progestogen (red tablets). Start the next pack immediately after finishing one, with no break between packs.

What to Expect

A withdrawal bleed is expected during or shortly after the red tablet phase at the end of each pack. If you miss a tablet and fewer than 12 hours have passed, take it as soon as you remember and continue as normal. If more than 12 hours have passed, skip the missed tablet. Missing progestogen-phase tablets may affect endometrial protection, contact your doctor if several are missed.

One tablet daily, taken continuously, following the sequential order of the pack:

• Days 1-16: One white tablet daily (estradiol 2 mg only)
• Days 17-28: One red tablet daily (estradiol 2 mg + norethisterone acetate 1 mg)

A new pack is started immediately after the last tablet. A withdrawal bleed typically occurs during or shortly after the red phase. If the bleed does not occur or becomes significantly irregular, a doctor should be consulted to exclude endometrial pathology.

Novofem is not recommended in women with significant hepatic impairment, as oestrogen and progestogen metabolism may be impaired. It is not suitable for use in women who have had a hysterectomy (oestrogen-alone HRT is appropriate in that case, as endometrial protection is not needed). No dose adjustment is available - Novofem is a fixed-dose preparation. Women who require a lower oestrogen dose may need an alternative HRT preparation.

Common Side Effects

The following side effects are commonly associated with combined sequential HRT:

• Breast tenderness or swelling (often worst during the progestogen phase)
• Headache or migraine
• Nausea and gastrointestinal discomfort
• Bloating and abdominal cramps
• Mood changes, including low mood or irritability (often progestogen-related)
• Irregular vaginal bleeding or spotting (particularly in the first three to six months)
• Leg cramps
• Fluid retention and peripheral oedema
• Acne or oily skin (due to the androgenic activity of norethisterone)
• Decreased libido

Serious Side Effects

Serious adverse effects require immediate medical attention:

• Venous thromboembolism (VTE) - deep vein thrombosis or pulmonary embolism; symptoms include sudden leg pain and swelling, breathlessness, or chest pain; combined HRT increases VTE risk approximately twofold
• Breast cancer - the risk of breast cancer is increased with combined oestrogen-progestogen HRT; the increase becomes apparent after approximately one year of use and diminishes after stopping
• Cardiovascular events - stroke and myocardial infarction risk is increased slightly, particularly in older postmenopausal women
• Endometrial carcinoma if the progestogen phase is consistently inadequate or missed
• Liver tumours (rare)
• Gallbladder disease - oral oestrogen increases the risk of gallstones and cholecystitis

Cancer and Cardiovascular Risks

Combined HRT, including Novofem, carries an increased risk of breast cancer with prolonged use. The absolute risk increase is approximately 5 additional cases per 1,000 women after 5 years of use, though risk varies with age, duration, and individual factors. Women should be encouraged to attend routine breast screening (mammography) and to perform regular breast self-examination. The breast cancer risk diminishes after stopping HRT but may take several years to fully return to baseline. Novofem also increases VTE risk by approximately two times the background population risk. Women with additional VTE risk factors (obesity, prolonged immobility, prior thrombosis, thrombophilia) should have a careful benefit-risk assessment before starting HRT.

Monitoring and Interactions

Women using Novofem should have an annual review with their doctor to reassess the benefit-risk balance and discuss whether continuing, adjusting, or stopping HRT is appropriate. Blood pressure should be checked regularly. Novofem's effectiveness may be reduced by enzyme-inducing medicines (rifampicin, some antiepileptics, St John's Wort), which increase the metabolism of both oestrogen and progestogen. Novofem is not contraceptive - perimenopausal women who may still be fertile (less than 12 months after last period) should use non-hormonal contraception in addition to Novofem. Novofem is contraindicated during pregnancy and breastfeeding.

Novofem must not be used in patients with:

• Known, suspected, or history of breast cancer
• Known or suspected oestrogen-sensitive malignancy (e.g., endometrial cancer)
• Undiagnosed vaginal bleeding
• Untreated endometrial hyperplasia
• Active or history of venous thromboembolism (DVT, pulmonary embolism) not adequately anticoagulated
• Active or recent arterial thromboembolic disease (angina, myocardial infarction, stroke)
• Active liver disease or severe hepatic impairment
• Known thrombophilic disorders (e.g., protein C or S deficiency, antiphospholipid syndrome) without specialist review
• Porphyria cutanea tarda
• Known hypersensitivity to estradiol, norethisterone acetate, or any excipient
• Pregnancy and breastfeeding
• Women who have had a hysterectomy (oestrogen-alone HRT is appropriate; progestogen is not needed)