Estradiol implants in HRT

• subcutaneous oestradiol and testosterone implants are specialist-only hormone replacement options used primarily for refractory menopausal symptoms or surgical menopause when standard transdermal/oral preparations are ineffective or unsuitable (1, 2)
• implants provide long-acting, steady parenteral release over several months, bypassing hepatic first-pass metabolism (1)
• all hormone implants are currently unlicensed in the UK and must be managed exclusively within specialist menopause services (2)

Clinical Indications and Administration

Patient Selection

• oestradiol implants: indicated for severe vasomotor or psychological symptoms persisting despite optimized standard HRT, or in young women following surgical menopause (oophorectomy) requiring higher physiological oestradiol levels (1, 2)
• testosterone implants: indicated for postmenopausal women with hypoactive sexual desire disorder (HSDD) / persistent distressing low libido where conventional HRT alone is ineffective (2)
• essential progestogen cover: women with an intact uterus who receive oestradiol implants require adequate ongoing systemic or intra-uterine progestogen (e.g., Mirena 52 mg IUD) to prevent endometrial hyperplasia; because residual implant tissue continues releasing oestrogen, progestogen protection must be maintained for up to 2 years after the final implant (2)

Dosing and Subcutaneous Insertion Procedure

• oestradiol doses: typically 25 mg or 50 mg pellets inserted every 4 to 8 months (1, 2)
• testosterone doses: 100 mg pellet inserted every 3 to 6 months (2)
• procedure: minor outpatient procedure performed under local anaesthesia; a small incision is made in the subcutaneous fat of the lower abdomen or buttock, the pellet is deposited via a trochar, and the wound is closed with adhesive strips or sutures (1, 2)

Disadvantages, Risks, and Complications

Lack of Reversibility

• once inserted, subcutaneous implants cannot be removed; if adverse effects occur or symptoms change, treatment cannot be rapidly discontinued (1, 2)
• variable duration: therapeutic effect typically lasts 4 to 8 months, but residual hormone release can persist for 18 to 24 months (2)

Tachyphylaxis and Hormone Accumulation

• tachyphylaxis risk: supraphysiological oestradiol spikes can occur, followed by a rapid return of climacteric symptoms (e.g., hot flushes) as levels fall, despite total serum oestradiol remaining well above normal (1, 2)
• risk of repeat insertion: patients experiencing early return of symptoms may request premature repeat implantation, leading to severe hormone accumulation (1, 2)
• mandatory monitoring: serial serum total testosterone or oestradiol levels must be checked before repeat implantation to prevent supraphysiological accumulation (e.g., keeping oestradiol < 800 pmol/L and Free Androgen Index < 5%) (2)

Supply and Licensing Status in the UK

• unlicensed status: subcutaneous hormone pellets lack a formal UK marketing authorization and are imported or supplied under special provisions (2)
• distribution in the UK: following previous commercial discontinuations (e.g., MSD discontinuing testosterone implants in 2012), 100 mg testosterone implants and 25 mg / 50 mg oestradiol implants (manufactured by Advanced Pharmaceutical Technology Inc, USA) are distributed in the UK via Smartway Pharmaceuticals Ltd (2)

Reference:

1. Hunter MS. Subcutaneous hormone implants for the control of climacteric symptoms. BMJ. 1989;299(6700):601-602. DOI: 10.1136/bmj.299.6700.601.
2. British Menopause Society (BMS). Subcutaneous Hormone Implant Therapy. BMS Practice Update & Guidance. Published September 2015; updated February 2025.