Oestrogen tablets, patches, gel and spray

Generic Name: Oestrogen (also spelled Estrogen)
Formulations Covered: Tablets, Patches, Gel, and Spray
Drug Class: Female Sex Hormones (Estrogens)

Common Synthetic Forms: Estradiol (most common), Conjugated Estrogens (e.g., Premarin), Estriol (rare)

Primary Indication: Hormone Replacement Therapy (HRT) for estrogen deficiency
Other Indications: Osteoporosis prevention, urogenital atrophy, menstrual disorders, transgender hormone therapy

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Clinical Indications

1. Hormone Replacement Therapy (HRT) in Postmenopausal Women
   – Alleviation of vasomotor symptoms (e.g., hot flashes, night sweats)
   – Treatment of vaginal atrophy, dryness, dyspareunia
   – Prevention of postmenopausal osteoporosis (when other options are unsuitable)

2. Premature Ovarian Insufficiency (POI)
   – HRT initiated before the average age of natural menopause to maintain bone and cardiovascular health

3. Hypoestrogenism
   – Due to surgical menopause, hypogonadism, or Turner syndrome

4. Menstrual Regulation
   – Management of amenorrhea, oligomenorrhea, or menstrual irregularity

5. Gender-Affirming Hormone Therapy
   – Feminizing therapy in transgender women

6. Palliative Care in Certain Cancers (historical)
   – Rarely used today for breast or prostate cancer

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Mechanism of Action

Oestrogen exerts its effects by binding to estrogen receptors (ERα and ERβ) in various tissues, regulating gene expression and protein synthesis. Its systemic effects include:

• Reproductive System: Maintains vaginal and uterine health, regulates menstrual cycle

• Skeletal System: Reduces bone resorption, preventing osteoporosis

• Cardiovascular System: Improves lipid profile, vasodilation (though cardiovascular risks are formulation-dependent)

• CNS: Modulates thermoregulation, mood, sleep

• Skin and Connective Tissue: Improves skin elasticity and hydration

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Formulations and Administration

1. Oral Tablets

• Examples:
  – Estradiol (e.g., Progynova, Estrace)
  – Conjugated estrogens (e.g., Premarin)
  – Estriol (e.g., Ovestin – rare)

• Strengths:
  – Estradiol: 1 mg, 2 mg
  – Conjugated estrogens: 0.3 mg, 0.625 mg, 1.25 mg

• Administration: Once daily with or without food

• Uses: Systemic HRT for vasomotor symptoms, urogenital symptoms, and osteoporosis prevention

• Advantages:
  – Convenient, widely available
  – Easy to titrate dose

• Disadvantages:
  – Undergoes first-pass metabolism → may affect liver protein synthesis (e.g., clotting factors)
  – Slightly increased risk of venous thromboembolism (VTE) and stroke

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2. Transdermal Patches

• Examples: Evorel, Estradot, Climara

• Strengths:
  – Estradiol content: 25 mcg/day to 100 mcg/day
  – Worn for 3–7 days, depending on brand

• Administration: Apply to clean, dry skin (e.g., buttocks, lower abdomen); rotate site

• Uses:
  – First-line option for osteoporosis prevention and women at risk of VTE
  – Fewer hepatic effects (no first-pass metabolism)

• Advantages:
  – Steady hormone delivery
  – Lower risk of VTE, stroke, and gallbladder disease than oral forms
  – Useful for women with migraine, liver disease, or gastrointestinal disorders

• Disadvantages:
  – Skin irritation at site
  – May detach prematurely in hot climates or with sweating

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3. Transdermal Gel

• Examples: Sandrena, Estrogel

• Strengths:
  – Estradiol: 0.5 mg, 1 mg, 1.5 mg, 2 mg/day

• Administration:
  – Applied once daily to arms, thighs, or abdomen
  – Allow to dry before dressing or contact

• Uses:
  – Alternative to patches for women preferring non-tablet options
  – Customizable dosing

• Advantages:
  – Rapid absorption
  – Avoids liver metabolism
  – Lower clotting risk than oral forms

• Disadvantages:
  – Transfer risk to partners through skin contact
  – Requires daily routine

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4. Transdermal Spray

• Example: Lenzetto

• Strengths:
  – Each spray delivers 1.53 mg estradiol

• Administration:
  – Spray once or twice daily to inner forearm; allow to dry
  – Avoid washing for at least 1 hour

• Uses:
  – Same indications as gel and patch

• Advantages:
  – Discreet and fast-drying
  – Easy to apply precisely
  – Lower clotting risk

• Disadvantages:
  – Potential transfer to others
  – Skin irritation

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Dosage Considerations

• Postmenopausal women (standard HRT):
  – Oral estradiol: 1–2 mg/day
  – Patch: 25–100 mcg/day
  – Gel: 0.5–1.5 mg/day
  – Spray: 1–2 sprays/day

• Hypoestrogenism or POI:
  – Often require higher doses (e.g., 2 mg oral estradiol or 100 mcg patch)

• Transgender women (adult):
  – Estradiol (oral): 2–6 mg/day
  – Estradiol patch: 100–200 mcg/day
  – Gel: up to 3 mg/day

Dose is individualized based on symptom control, risk factors, and patient preference.

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Adverse Effects

Common Side Effects:

• Nausea

• Headache

• Breast tenderness

• Bloating

• Mood changes

• Vaginal bleeding or spotting

• Leg cramps

Serious Risks:

• Venous thromboembolism (VTE) – higher with oral forms

• Stroke and myocardial infarction – especially in older women with comorbidities

• Endometrial hyperplasia/cancer – in women with an intact uterus if unopposed by progestogen

• Breast cancer – long-term use (especially ≥5 years) associated with slightly increased risk

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Contraindications

• Active or past breast cancer

• Known or suspected estrogen-dependent tumor

• Undiagnosed vaginal bleeding

• Active thromboembolic disease

• Active or recent arterial thromboembolism (e.g., stroke, MI)

• Severe liver dysfunction or disease

• Pregnancy

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Precautions and Monitoring

• Always co-administer with progestogen in women with an intact uterus to prevent endometrial cancer

• Review therapy annually and assess continued need

• Baseline assessments: Blood pressure, breast exam, BMI, lipid profile, family history of cancer

• Monitoring during therapy:
  – Annual breast exams
  – Periodic pelvic exams
  – Mammography as per national guidelines
  – Monitor for new onset of abnormal bleeding

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Drug Interactions

• Enzyme inducers (e.g., phenytoin, rifampin, carbamazepine): Reduce efficacy of oral estrogens

• Thyroxine (levothyroxine): Estrogens may increase thyroxine-binding globulin → adjust dose

• Corticosteroids: Estrogens may increase circulating corticosteroid levels

• St. John’s Wort: May reduce estrogen efficacy

• Warfarin: Estrogens may reduce anticoagulant effectiveness

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Patient Counseling

• Apply gel, spray, or patch as directed; rotate sites; avoid heat or occlusion

• Do not apply estrogen gel or spray near breasts or genital area

• Wait at least 1 hour before showering after applying gel or spray

• Report any unusual vaginal bleeding, calf pain, shortness of breath, or chest pain

• Do not share topical products due to risk of transference

• Estrogen therapy is not a contraceptive

• Smoking cessation is strongly advised (increases thrombotic risk)

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Comparative Summary of Forms

Form	First-Pass Metabolism	VTE Risk	Dosing Frequency	Transfer Risk	Patient Preference
Tablet	Yes	Higher	Daily	None	Preferred for convenience
Patch	No	Lower	Twice weekly	None	Useful in liver/GI issues
Gel	No	Lower	Daily	Yes	Flexible dosing
Spray	No	Lower	Daily	Yes	Discreet, dries fast

Storage and Handling

• Store at room temperature (20–25°C)

• Avoid exposure to direct sunlight and heat

• Keep topical products out of reach of children

• Do not apply heat (e.g., heating pads) over patch

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Regulatory Notes

• All forms are prescription-only

• Included in NICE, EMA, MHRA, and FDA guidelines for menopause and POI management

• Estrogen-only HRT should not be prescribed without risk assessment

• Duration of use should be as short as possible for the intended purpose