What is the appropriate management for a 54‑year‑old woman with depression and anxiety who has elevated follicle‑stimulating hormone (FSH) and luteinizing hormone (LH), low‑normal estradiol (E2), low testosterone (T), low progesterone (P), and normal prolactin (PRL) according to Canadian laboratory reference ranges?

Management of Perimenopausal Transition with Mood Symptoms

This 54-year-old woman is in late perimenopause based on her elevated FSH (27.7) and LH (23.7) with relatively preserved estradiol (236 pmol/L), and her depression and anxiety are likely related to hormonal fluctuations characteristic of this transition; she should be offered estrogen-based hormone therapy to stabilize mood and manage perimenopausal symptoms, combined with continued or optimized psychiatric treatment. 1, 2

Interpretation of Hormone Profile

Menopausal Status Classification

• Her FSH of 27.7 IU/L and LH of 23.7 IU/L are elevated into the perimenopausal-to-postmenopausal range, indicating declining ovarian reserve, though she has not yet reached definitive menopause since her estradiol remains detectable at 236 pmol/L (approximately 64 pg/mL). 1, 3

• At age 54 with these hormone levels, she does not require laboratory confirmation of menopause for clinical management, as women ≥60 years can be diagnosed by age alone, and she is approaching this threshold with clear biochemical perimenopause. 1

• The combination of elevated gonadotropins (FSH/LH) with fluctuating but still-present estradiol is classic for late perimenopause, where residual follicles undergo irregular maturation with diminished responsiveness to gonadotropin stimulation. 4, 3

Hormone-Mood Relationship

• Her low progesterone (1.7 nmol/L, approximately 0.53 ng/mL) indicates anovulation, which is typical in perimenopause and contributes to unopposed estrogen effects and mood instability. 2, 3

• Depression and anxiety during perimenopause are strongly associated with hormonal fluctuations rather than absolute hormone deficiency, as perimenopausal women with mood symptoms do not show consistent differences in basal estradiol, FSH, or LH compared to asymptomatic controls. 5, 6

• Her testosterone level of 1.52 nmol/L (approximately 44 ng/dL) is in the normal range for perimenopausal women, and low testosterone is not the primary driver of her symptoms. 6

• Normal prolactin (19.2 µg/L) rules out hyperprolactinemia as a contributor to mood symptoms or menstrual irregularity. 7

Treatment Algorithm

Hormone Replacement Therapy

Initiate transdermal estradiol starting at 0.025-0.05 mg/day (1-2 mg oral equivalent), as this is the lowest effective dose for managing vasomotor and mood symptoms in perimenopause. 8

• Because she has an intact uterus (implied by progesterone measurement), she requires concurrent progestogen therapy to prevent endometrial hyperplasia: prescribe micronized progesterone 100-200 mg daily or medroxyprogesterone acetate 2.5-5 mg daily. 2, 8

• Estrogen therapy should be cyclic initially (3 weeks on, 1 week off) to mimic physiologic patterns, though continuous combined therapy is an alternative if breakthrough bleeding occurs. 8

• Reassess symptom control at 3-6 month intervals and use the lowest effective dose; if depression and anxiety improve, continue therapy through the menopausal transition and reassess need after age 60. 8

Psychiatric Management

• Continue or optimize her current antidepressant/anxiolytic regimen, as hormone therapy alone may not fully resolve established depression and anxiety, though it can significantly augment response. 5, 6

• Avoid paroxetine or fluoxetine if she is taking tamoxifen (though not indicated in this case), as these inhibit CYP2D6 and reduce tamoxifen efficacy. 7

• Consider cognitive behavioral therapy or clinical hypnosis as adjunctive non-pharmacologic interventions for mood symptoms and any vasomotor symptoms. 7

Monitoring and Follow-Up

• Repeat hormone testing is not necessary for ongoing management, as clinical symptom response guides therapy adjustments, not laboratory values. 1

• If she develops amenorrhea for ≥12 months while on hormone therapy, she can be considered postmenopausal, but therapy should continue until at least age 60 given her current age and symptom burden. 1, 2

• Perform endometrial sampling if she experiences undiagnosed persistent or recurrent abnormal vaginal bleeding while on hormone therapy to rule out hyperplasia or malignancy. 8

Bone and Cardiovascular Protection

• Initiate calcium 1200-1500 mg daily with vitamin D 800-1000 IU daily, as premature estrogen deficiency increases osteoporosis risk, and consider baseline DEXA scan. 2

• Estrogen therapy initiated at age 54 (within 10 years of expected menopause) provides cardiovascular benefit and reduces all-cause mortality when started before age 60. 2

• Monitor lipid profile, as estrogen deficiency increases LDL and decreases HDL; address modifiable cardiovascular risk factors including smoking cessation and blood pressure control. 2

Common Pitfalls to Avoid

• Do not withhold hormone therapy based on outdated concerns about cardiovascular or breast cancer risk in this age group, as current evidence supports net benefit for symptomatic women under 60 within 10 years of menopause onset. 2

• Do not rely on single FSH measurements to definitively diagnose menopause in women under 60, as FSH fluctuates widely during perimenopause and can transiently reach postmenopausal levels before returning to premenopausal ranges. 4, 3

• Do not prescribe estrogen without progestogen in a woman with an intact uterus, as unopposed estrogen significantly increases endometrial cancer risk. 8

• Do not assume mood symptoms will resolve with hormone therapy alone; integrated psychiatric care is essential for women with established depression and anxiety. 5, 6