Replacing estrogen, usually with progesterone, relieves hot flushes and night sweats, restores genital and urinary tissue, reduces broken bones, lowers adult-onset diabetes, and improves sleep broken by night sweats. Transdermal estrogen appears to avoid the clot and stroke excess of oral estrogen. Synthetic progesterone substitutes raise breast cancer risk. Starting near menopause appears to matter, though that evidence is contradictory. (Full Review)

Protocol

Standard contemporary regimen

Transdermal estradiol 25–100 µg daily by patch

Or 0.75–1.5 mg daily by gel, plus oral micronized progesterone in women with a uterus.

Cyclical versus continuous progestogen

Micronized progesterone 100 mg nightly, or 200 mg nightly 12–14 days monthly

Continuous after menopause for amenorrhoea (no bleeding); cyclical while still bleeding. Taken at bedtime.

Local therapy as a standalone option

Vaginal estradiol 10 µg tablet or estriol 0.5 mg cream

Nightly for two weeks, then twice weekly indefinitely. No progestogen required; systemic absorption is negligible.

Time to effect

Hot flushes

2–4 weeks

Plateau by 12 weeks; sleep and mood follow the same curve.

Bone density

12 months

Time needed before a change is measurable on scan.

Genitourinary symptoms

8–12 weeks

With vaginal estrogen.

Benefits

High: Relief of vasomotor symptoms; prevention of osteoporotic fracture; relief of genitourinary syndrome of menopause; lower incidence of type 2 diabetes; improved sleep quality in women with night sweats; improved sexual function with added testosterone

Medium: Prevention of depressive symptoms during the menopause transition; reduced joint pain and stiffness

Low: Reduced coronary heart disease risk with early initiation; lower death from any cause with early initiation; preserved cognitive function with early initiation; reduced colorectal cancer incidence

Speculative: Slower epigenetic ageing

Contraindications

Current, past, or suspected hormone-receptor-positive breast cancer, any interval since treatment

Active or recent (3–6 months) venous thromboembolism, or high-risk thrombophilia (homozygous Factor V Leiden, antithrombin deficiency)

Myocardial infarction, unstable angina, or ischaemic stroke within 12 months, or symptomatic coronary artery disease

Active liver disease with ALT above 3× the upper limit of normal, or Child-Pugh B or C cirrhosis

Untreated endometrial hyperplasia, active endometrial cancer, or uninvestigated unexplained postmenopausal bleeding

Known or suspected pregnancy

Fasting triglycerides above 500 mg/dL when oral estrogen is proposed

Systemic therapy after age 60, or over 10 years past the final menstrual period, without vasomotor symptoms

Tamoxifen and aromatase inhibitors (anastrozole, letrozole, exemestane)

Combined oral contraceptives and other exogenous estrogens

Key Interactions

CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, efavirenz)

CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin, diltiazem)

Levothyroxine

Lamotrigine

Anticoagulants (warfarin, apixaban, rivaroxaban)

Corticosteroids (prednisolone, dexamethasone) and ciclosporin

Acetaminophen (paracetamol)

Orlistat (alli)

St John's wort

Phytoestrogen supplements (soy isoflavones, red clover, black cohosh, Pueraria mirifica)

DHEA

Risk & Side Effects

High: Venous thromboembolism with oral routes; ischaemic stroke; breast cancer with estrogen-progestogen regimens; endometrial hyperplasia and cancer with unopposed estrogen; gallbladder disease requiring surgery; vaginal bleeding and breast tenderness

Medium: Dementia when started after age 65; ovarian cancer; urinary incontinence with systemic therapy; raised blood pressure with oral estrogen

Low: Coronary events when started long after menopause; lung cancer mortality with estrogen-progestogen; meningioma

Monitoring

Marker	Target	Why
Estradiol (E2)	50–100 pg/mL, transdermal	Confirms absorption and guides titration
FSH	No established on-treatment target	Confirms menopausal status before starting
Blood pressure	Below 120/80 mmHg	Oral estrogen raises it
ApoB	Below 80 mg/dL	Best single marker of atherogenic particle burden
Triglycerides	Below 100 mg/dL	Oral estrogen raises them; pancreatitis above 500 mg/dL
HbA1c	4.8–5.4%	Tracks the glycaemic benefit and detects deterioration
ALT	Below 20 U/L	Screens for hepatic injury and fatty liver
TSH	0.5–2.5 mIU/L	Oral estrogen raises thyroid hormone requirement
SHBG	30–90 nmol/L	Oral estrogen raises it, lowering free testosterone
Total testosterone	20–70 ng/dL if testosterone used	Prevents supraphysiological dosing
25-hydroxyvitamin D	40–60 ng/mL	Required for the fracture benefit to be realised
Bone mineral density (DXA T-score)	Above −1.0	Objective measure of the skeletal benefit
Endometrial thickness (transvaginal ultrasound)	Below 4 mm off therapy; below 8 mm sequential	Detects inadequately opposed estrogen effect

Cadence: Symptom and side-effect review at 6–8 weeks; full review with blood pressure and weight at 3 and 6 months, then annually. Lipids, glucose, liver enzymes annually. Bone density 2-yearly where it guided the decision; mammography 2-yearly.

Qualitative Assessment

Frequency and severity of hot flushes and night sweats, scored weekly for three months
Sleep continuity — night-time awakenings and subjective restedness on waking
Mood stability, irritability, and anxiety, ideally against a written pretreatment baseline
Cognitive clarity and word-finding
Vaginal comfort, absence of pain during intercourse, and urinary urgency or frequency
Sexual desire and satisfaction, especially where testosterone has been added
Joint pain and morning stiffness
Energy, exercise tolerance, and whether training capacity has returned toward premenopausal levels

Female HRT for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment