What approach should I take when a woman presents with concerns about hormonal imbalance?

Systematic Approach to Hormonal Concerns in Women

When a woman presents wanting to discuss hormones, begin with a focused menstrual and symptom history to determine if she has amenorrhea, irregular cycles, vasomotor symptoms, or genital symptoms, as each requires distinct diagnostic and management pathways. 1

Initial Assessment Framework

Key Historical Elements to Obtain

• Menstrual pattern specifics: Document cycle regularity, duration of amenorrhea if present, and whether bleeding is absent versus irregular 1
• Vasomotor symptoms: Quantify hot flushes and night sweats, including frequency, severity, and impact on daily function 2
• Genital symptoms: Ask specifically about vaginal dryness, dyspareunia, and vulvar discomfort 2
• Reproductive history: Prior pregnancies, contraceptive use, and fertility concerns 2
• Cancer history: Any prior malignancy, particularly hormone-sensitive cancers, fundamentally alters management 2

Physical Examination Priorities

• Tanner staging in younger patients to assess pubertal development 2
• Signs of estrogen deficiency: Vaginal atrophy, skin changes, and body habitus 2
• Signs of hyperandrogenism: Hirsutism, acne, and virilization if irregular cycles present 1

Diagnostic Algorithm Based on Presentation

For Amenorrhea or Irregular Cycles

Order the following laboratory tests to establish the etiology: 1

• Serum prolactin: Elevated levels indicate hyperprolactinemia and potential pituitary adenoma requiring urgent MRI 1
• TSH: Essential to exclude thyroid dysfunction as a reversible cause 1
• FSH and LH (ideally cycle days 3-6 if any bleeding): Elevated FSH with low/normal LH indicates primary ovarian insufficiency; LH/FSH ratio >2 suggests PCOS 1
• Testosterone and androstenedione: If signs of hyperandrogenism present 1

Critical pitfall: Never assume amenorrhea is benign—prolonged hypoestrogenism increases osteoporosis and cardiovascular disease risk 1

For Vasomotor Symptoms

Hormone therapy is the most effective intervention for bothersome vasomotor symptoms in appropriate candidates. 2, 3

Candidate Selection for Hormone Therapy

Offer hormone therapy to women: 4

• Younger than 60 years OR within 10 years of menopause onset
• With bothersome vasomotor symptoms affecting quality of life
• Without contraindications (see below)

Absolute Contraindications to Systemic Hormone Therapy

• Hormone-sensitive breast cancer (current or history) 2
• Active cardiovascular disease 3
• History of venous thromboembolism 3
• Active liver disease 3
• Endometrial cancer (relative contraindication requiring specialist discussion) 2

Important nuance: Women with non-hormone-sensitive cancers who develop treatment-induced vasomotor symptoms should be counseled to consider hormone therapy until approximately age 51 (average menopause age), then re-evaluate 2

Hormone Therapy Regimen Selection

For women with intact uterus: 2

• Combined estrogen plus progesterone required to prevent endometrial hyperplasia
• Oral contraceptives or transdermal devices provide multiple formulation options

For women post-hysterectomy: 2

• Estrogen-only therapy (oral, transdermal, or vaginal) has more favorable risk/benefit profile

Use the lowest effective dose for the shortest duration necessary 3, 4

Alternative Options When Hormone Therapy Contraindicated

For women unable or unwilling to use hormone therapy: 2

• Paroxetine or venlafaxine (avoid paroxetine/fluoxetine in women taking tamoxifen due to drug interaction)
• Gabapentin
• Clonidine (caution: hypotension, dizziness, sedation; never stop abruptly due to rebound hypertension)
• Cognitive behavioral therapy or clinical hypnosis may provide benefit

For Genital/Vaginal Symptoms

Use a stepwise approach for vaginal/vulvar atrophy symptoms: 2

1. First-line: Vaginal lubricants for sexual activity PLUS vaginal moisturizers 3-5 times weekly applied to vagina, vaginal opening, and external vulva 2

2. Second-line (if inadequate response): Low-dose vaginal estrogen 2

   • Even in women with hormone-positive breast cancer, can be considered after thorough risk/benefit discussion if conservative measures fail 2

3. Additional options:

   • Lidocaine for persistent introital pain and dyspareunia 2
   • Vaginal dehydroepiandosterone for women on aromatase inhibitors not responding to other treatments 2
   • Vaginal dilators for vaginismus or vaginal stenosis 2

Referral Indications

Endocrinology/Gynecology Referral Required For:

• Prepubertal/peripubertal patients: No puberty signs by age 13, primary amenorrhea by age 16, or failure of pubertal progression 2
• Elevated prolactin levels: Requires pituitary MRI and specialist management 1
• Confirmed primary ovarian insufficiency: FSH elevation with amenorrhea requires specialist counseling about unpredictable ovarian function and fertility preservation 2, 1
• Persistent menstrual dysfunction suggesting premature ovarian insufficiency in cancer survivors 2

Reproductive Endocrinology Referral For:

• Women desiring fertility assessment after gonadotoxic therapy 2
• Consideration of oocyte cryopreservation for fertility preservation 2

Special Populations

Cancer Survivors

For women treated with gonadotoxic chemotherapy or pelvic radiation: 2

• Annual assessment of menstrual history and pubertal progression until sexual maturity
• Baseline FSH, LH, and estradiol at age 13 in prepubertal survivors
• Bone mineral density testing for hypogonadal patients
• Counsel about variable gonadotoxicity—contraception still needed despite treatment 2

Critical consideration: AMH is not recommended as the primary surveillance modality but may be reasonable in conjunction with FSH/estradiol in survivors ≥25 years 2

Hormone Replacement Timing in Hypogonadism

For prepubertal patients: Timing and tempo of estrogen replacement crucial for acceptable final height—requires pediatric endocrinologist management 2

For postmenarchal women: If amenorrheic during/after cancer therapy, monitor for menses resumption for 1 year; if persistent amenorrhea or elevated gonadotropins, offer hormone replacement in consultation with specialist 2

Documentation and Counseling Essentials

• Contraception counseling: Even women at risk of early menopause need contraception due to variable ovarian function 2
• Bone and cardiovascular health: Emphasize benefits of hormone replacement therapy in promoting bone mineral density and cardiovascular health in hypogonadal patients 2
• Stress dosing education: For women on corticosteroid replacement, provide education on stress dosing, emergency injectables, and medical alert identification 2