What is the weight‑based dosing guidance for subcutaneous testosterone pellets (Testopel® [testosterone]) and estradiol pellets in women, including recommended starting doses, dosing intervals, and monitoring parameters?

Weight-Based Dosing Guidance for Testosterone and Estradiol Pellets in Women

Testosterone Pellet Dosing in Women

For subcutaneous testosterone pellets in women, initiate therapy with 100 mg (one pellet) regardless of body weight, as pharmacologic dosing (serum levels 170–300 ng/dL) is required to produce physiologic clinical effects, and weight-based dosing is not supported by current evidence. 1

Initial Dosing Strategy

• Standard starting dose: 100 mg testosterone pellet for all women with androgen deficiency symptoms, irrespective of weight 1
• The majority of sexual medicine specialists (80.5%) use ≥10 pellets (≥1000 mg) for male hypogonadism, but this dosing does not apply to women 2
• In women, therapeutic serum testosterone levels of 299 ng/dL at 4 weeks and 171 ng/dL when symptoms return are achieved with lower doses than used in men 1

Monitoring and Redosing Intervals

• Measure serum testosterone at 4 weeks after initial implantation to assess peak levels (expected range 200–400 ng/dL) 1
• Redose when symptoms return, typically at 4–6 month intervals based on clinical response rather than arbitrary timing 3, 1
• Serum testosterone levels when symptoms recur average 171 ± 73 ng/dL, providing a clinical threshold for reimplantation 1

Key Monitoring Parameters

• Significant inter-individual variance exists (coefficient of variation 36–43%), making single testosterone measurements unreliable for dose adjustment 1
• Intra-individual circadian variation is also substantial (CV 25%), further limiting the utility of isolated measurements 1
• Clinical response, safety, and tolerability should guide therapy rather than targeting specific serum testosterone levels 1

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Estradiol Pellet Dosing in Women

Initiate estradiol pellet therapy with 25 mg for most women, which achieves physiologic early-to-mid follicular phase levels (50–70 pg/mL) and provides effective symptom control without weight-based adjustment. 4, 3

Initial Dosing by Clinical Indication

• Standard starting dose: 25 mg estradiol pellet for climacteric symptom relief and osteoporosis protection 3
• Dose range: 25–75 mg depending on severity of estrogen deficiency and prior treatment response 5
• The 25 mg dose produces mean estradiol levels of 50–70 pg/mL, effectively controls vasomotor symptoms, and increases bone mineral density 4
• Higher doses (50–75 mg) achieve peak levels of 150–190 pg/mL but do not provide superior clinical efficacy for most indications 5, 4

Pharmacokinetic Profile

• Peak estradiol levels occur within 2 weeks of implantation (mean 190 ± 35 pg/mL with 75 mg dose) 5
• Stable levels are maintained for 4–6 months within the early-to-mid follicular range (50–113 pg/mL depending on dose) 4
• After 75 mg implantation, estradiol levels average 125 pg/mL for up to 70 weeks, though most patients require redosing at 6 months 5
• Estradiol pellets maintain a near-physiological E2:E1 ratio of approximately 1.5:1, superior to oral formulations 4

Redosing Intervals and Monitoring

• Redose approximately every 6 months for most patients, guided by return of climacteric symptoms combined with serum estradiol levels 3
• Measure FSH and LH at baseline (should be elevated in estrogen-deficient states) and at 4–6 weeks post-implantation to confirm adequate suppression 5
• FSH and LH suppression occurs within 4–6 weeks and correlates with estradiol dose; incomplete suppression with 25 mg suggests need for higher dosing 5
• Monitor serum estradiol levels at 1 month, then every 3–6 months to avoid supraphysiological levels and tachyphylaxis 4

Endometrial Protection (Critical Safety Requirement)

• All women with an intact uterus require progestogen therapy to protect the endometrium, identical to other estrogen replacement regimens 3
• Administer oral progestogen cyclically (e.g., 10–14 days per month) to induce regular withdrawal bleeding 5
• Bleeding complications and endometrial hyperplasia are primarily associated with excessive dosing, premature reimplantation, or lack of progestogen protection 4

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Combined Testosterone and Estradiol Pellet Therapy

• Testosterone 75 mg can be co-implanted with estradiol 25–75 mg at the same procedure for women requiring both hormone replacements 5
• Testosterone levels peak at 2.5 ± 1.6 ng/mL within 2 weeks, then decline steadily to baseline by 17–18 weeks, necessitating more frequent testosterone redosing than estradiol 5
• The E2:E1 ratio is significantly higher in women receiving estradiol alone versus combined estradiol + testosterone implants during the first 18 weeks 5

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Common Pitfalls to Avoid

• Do not use weight-based dosing for testosterone pellets in women, as the evidence demonstrates that pharmacologic serum levels (not weight-adjusted doses) are required for clinical effect 1
• Do not rely on single testosterone measurements for dose titration due to extreme inter- and intra-individual variability (CV 36–43%); use clinical response instead 1
• Do not reimplant estradiol pellets prematurely (before 4–6 months) as this causes supraphysiological levels, tachyphylaxis, and increased bleeding risk 4
• Do not omit progestogen therapy in women with an intact uterus receiving estradiol pellets, as endometrial protection is mandatory 3
• Do not assume higher estradiol doses (50–75 mg) provide superior efficacy; the 25 mg dose is effective for most indications and minimizes safety concerns 4, 3