Utrogestan

Utrogestan contains micronised natural progesterone, identical in molecular structure to endogenous progesterone produced by the corpus luteum.

It is licensed for hormone replacement therapy (HRT) as the progestogen component in women with an intact uterus receiving oestrogen replacement, and for the management of luteal insufficiency in assisted reproductive technology (ART) cycles.

Micronised progesterone is preferred over synthetic progestogens by many clinicians due to evidence suggesting a more favourable safety profile, particularly regarding breast cancer risk and venous thromboembolism.

The NICE guideline on menopause (NG23) acknowledges micronised progesterone as an option for endometrial protection during HRT.

It can be taken orally or used vaginally (off-label for HRT in the UK, on-label for ART).

The oral route undergoes significant first-pass hepatic metabolism, producing the active metabolite allopregnanolone, which has sedative anxiolytic properties.

This pharmacological characteristic makes bedtime dosing advantageous.

Utrogestan is also used in some protocols for luteal phase support in fertility treatment and for managing certain causes of abnormal uterine bleeding.

For HRT (endometrial protection): Take 200 mg orally at bedtime on days 1-12 (or 1-14) of each 28-day oestrogen replacement cycle (sequential regimen), or 100 mg daily continuously alongside continuous oestrogen (continuous combined regimen).

Swallow capsules whole with water on an empty stomach, as food increases bioavailability unpredictably. Taking the dose at bedtime minimises drowsiness from the sedative metabolite allopregnanolone.

For ART (luteal phase support): Insert 200-400 mg vaginally per day, typically starting from the day of embryo transfer or oocyte retrieval, and continue for 10-12 weeks or as directed by your fertility specialist.

Do not chew or break the capsules. If you miss an oral dose, take it when remembered unless it is nearly time for the next dose.

Sequential HRT: 200 mg orally at bedtime for 12-14 days per 28-day cycle.

Continuous combined HRT: 100 mg orally at bedtime daily.

Luteal phase support (ART): 200-400 mg vaginally per day, divided into one or two doses.

Doses above 200 mg orally should be split (e.g. 100 mg in the morning and 200 mg at bedtime), though single bedtime dosing of 200 mg is standard.

In hepatic impairment, oral bioavailability may be altered; vaginal administration avoids first-pass metabolism and may be preferable. No dose adjustment is needed for renal impairment.

Side effects are from SmPC data and clinical experience.

Common (≥1/100 to <1/10): Drowsiness and somnolence (particularly with oral dosing, attributed to allopregnanolone), headache, dizziness, abdominal bloating, nausea, breast tenderness, altered menstrual bleeding pattern.

Uncommon (≥1/1,000 to <1/100): Depression, insomnia, acne, pruritus, urticaria, cholestatic jaundice, altered libido.

Rare (≥1/10,000 to <1/1,000): Chloasma, anaphylaxis, thromboembolism (though the risk with micronised progesterone appears lower than with synthetic progestogens based on observational data).

Vaginal administration is associated with local irritation and discharge but fewer systemic side effects such as drowsiness.

The sedative effect of oral administration is generally regarded as a benefit at bedtime rather than an adverse effect.

Utrogestan should be used as part of a combined HRT regimen in women with an intact uterus; unopposed oestrogen increases the risk of endometrial hyperplasia and carcinoma.

The MHRA advises that all HRT should be prescribed at the lowest effective dose for the shortest duration necessary, with regular clinical review (at least annually).

Data from the E3N cohort study and the KEEPS trial suggest micronised progesterone may have a lower breast cancer risk than synthetic progestogens, but no absolute safety guarantee can be given.

Patients with porphyria should use progesterone with caution. Avoid in patients with undiagnosed vaginal bleeding until the cause has been established.

Utrogestan is contraindicated in known or suspected breast cancer, known or suspected sex steroid-dependent malignancies, undiagnosed vaginal bleeding, active or recent arterial thromboembolism, active or history of venous thromboembolism (unless anticoagulated), severe hepatic impairment or active hepatic disease, hypersensitivity to progesterone or any excipient (the capsules contain soya lecithin and peanut oil — contraindicated in patients with peanut or soya allergy), and porphyria.