What is the appropriate management for a woman with elevated Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels and low Testosterone level?

Premature Ovarian Insufficiency (POI) - Diagnostic Confirmation and Management

This hormone profile (LH 47.6, FSH 15.7, testosterone 24) is diagnostic of premature ovarian insufficiency (POI), and the patient requires immediate hormonal replacement therapy with 17β-estradiol plus progestin, continued until the natural age of menopause (45-55 years). 1

Understanding the Hormone Pattern

The markedly elevated LH (47.6 IU/L) combined with elevated FSH (15.7 IU/L) and low testosterone indicates primary ovarian failure with compensatory pituitary hyperactivity. 1

Key diagnostic features:

• LH elevation is disproportionately high compared to FSH - this pattern is characteristic of POI, where LH often rises more dramatically than FSH in response to ovarian failure 2, 3
• Low testosterone (24 ng/dL) reflects loss of ovarian androgen production, which contributes to diminished libido and sexual dysfunction 1
• The FSH:LH ratio is inverted from typical postmenopausal patterns, where FSH usually exceeds LH more substantially 4, 5

Essential Diagnostic Workup Before Treatment

Complete these investigations immediately:

• Thyroid function tests (TSH, free T4) - thyroid dysfunction commonly coexists with POI and affects the hypothalamic-pituitary-gonadal axis 6
• Prolactin level - to exclude hyperprolactinemia as a contributing or confounding factor 1, 6
• Autoimmune screen including anti-thyroid peroxidase antibodies and anti-adrenal antibodies, as autoimmune POI is common 6
• Karyotype analysis if age <40 years to exclude Turner syndrome mosaicism 1
• Baseline bone mineral density (DEXA scan) - women with POI have accelerated bone loss and require monitoring 6

Hormonal Replacement Therapy - First-Line Treatment

Primary recommendation: 17β-estradiol-based hormone replacement therapy (HRT), NOT combined oral contraceptives. 1

Preferred Regimens (in order of preference):

First choice: Combined transdermal 17β-estradiol + progestin patches

• 17β-estradiol + levonorgestrel patches (if available in your country) 1
• Change twice weekly or weekly depending on formulation 1
• Sequential combined regimen (estrogen continuous, progestin 2 weeks per month) induces withdrawal bleeding 1
• Continuous combined regimen (both hormones continuously) avoids bleeding 1

Second choice: Transdermal 17β-estradiol patches + oral progestin

• 17β-estradiol patches 50-100 μg/24 hours, changed twice weekly 1
• Add micronized progesterone 200 mg orally for 12-14 days every 28 days (preferred progestin due to lower cardiovascular and thrombotic risk) 1
• Alternative progestins: dydrogesterone 10 mg for 12-14 days/month, or medroxyprogesterone acetate (MPA) 10 mg for 12-14 days/month 1
• Avoid progestins with anti-androgenic effects as they worsen hypoandrogenism and sexual dysfunction 1

Third choice: Oral 17β-estradiol + progestin (if transdermal contraindicated)

• 17β-estradiol 1-2 mg daily + dydrogesterone or MPA 1
• Use only when transdermal route is contraindicated (e.g., chronic skin conditions, skin graft-versus-host disease) 1

Why 17β-Estradiol Over Ethinyl Estradiol:

17β-estradiol is physiologic estrogen with lower thrombotic risk compared to synthetic ethinyl estradiol found in combined oral contraceptives. 1 While COCs may be prescribed if contraception is needed or for social acceptance, 17β-estradiol-based HRT is medically superior for long-term use in POI. 1

Duration of Treatment

Continue HRT until age 45-55 years (average age of natural menopause). 1 After reaching natural menopausal age, reassess risks, benefits, family history, and menopausal symptoms to decide whether to continue at lower postmenopausal doses. 1

Addressing Testosterone Deficiency

Testosterone replacement may be considered for persistent diminished libido or sexual dysfunction despite adequate estrogen replacement. 1 However, specific dosing recommendations for women with POI are limited in the guidelines provided. Endocrinology consultation is appropriate for testosterone supplementation. 1

Critical warning: Never prescribe exogenous testosterone alone without estrogen replacement - this would further suppress the hypothalamic-pituitary axis and worsen symptoms. 6

Cardiovascular and Bone Health Monitoring

Mandatory long-term monitoring:

• Cardiovascular risk assessment - women with POI have increased cardiovascular disease risk 6
• Bone density monitoring - repeat DEXA scans every 1-2 years initially, then adjust frequency based on results 6
• Annual breast imaging from age 25 if history of total body irradiation or Hodgkin lymphoma treatment 1
• Breast MRI may be superior to mammography in young women with dense breast tissue 1

Common Pitfalls to Avoid

Do not use FSH alone to diagnose POI - FSH shows marked variability during the menopausal transition, and single measurements can be misleading. 2, 7 The combination of elevated LH and FSH with low estradiol/testosterone is diagnostic. 1

Do not prescribe combined oral contraceptives as first-line therapy unless contraception is specifically needed - 17β-estradiol-based HRT has superior safety profile for long-term use. 1

Do not delay treatment - every year without estrogen replacement accelerates bone loss and increases cardiovascular risk. 6

Do not stop HRT at age 50-51 simply because this is "average menopause age" - continue until at least age 45-55, then individualize based on symptoms and risk factors. 1