Is it recommended to start hormonal therapy during pre-menopause while still having periods?

Hormonal Therapy Should Not Be Started During Pre-Menopause While Still Having Periods

For premenopausal women with hormone receptor-positive breast cancer, hormonal therapy must be combined with ovarian suppression or ablation—you cannot simply start endocrine therapy while maintaining normal menstrual cycles. 1

Context Clarification

The question appears to reference breast cancer treatment, as the evidence provided focuses on endocrine therapy for hormone receptor-positive disease. If this question pertains to menopausal hormone replacement therapy (HRT) for symptom management, the answer would be entirely different—HRT is contraindicated in breast cancer patients but may be appropriate for perimenopausal symptom relief in healthy women. 2, 3

For Breast Cancer Treatment in Premenopausal Women

Core Principle: Ovarian Suppression is Mandatory

Premenopausal women with HR-positive metastatic or early-stage breast cancer must receive ovarian suppression or ablation when starting endocrine therapy. 1

• The American Society of Clinical Oncology (ASCO) provides a strong recommendation (high-quality evidence) that premenopausal women should be offered ovarian suppression or ablation in combination with hormone therapy. 1

• There are no clinically important data supporting endocrine therapy in women who remain premenopausal without ovarian suppression. 1

• The ASCO panel "uniformly recommends that premenopausal women start ovarian suppression" before or concurrent with endocrine therapy initiation. 1

Why Ovarian Suppression is Required

Aromatase inhibitors (AIs) are contraindicated in premenopausal women without ovarian suppression because the reduction in tissue estrogen leads to increased gonadotropin secretion, causing compensatory rises in ovarian estrogen production and potential ovulation induction. 1

• Even tamoxifen alone, while possible, shows improved outcomes when combined with ovarian suppression compared to tamoxifen monotherapy. 1

• For premenopausal women without prior hormone therapy exposure, the preferred regimen is ovarian suppression plus tamoxifen OR ovarian suppression plus an AI (both Category 1 recommendations). 1

Treatment Algorithm for Premenopausal Women

First-line therapy options (all require ovarian suppression): 1

• Ovarian suppression + tamoxifen (5 years)
• Ovarian suppression + aromatase inhibitor (5 years)—particularly for higher-risk patients (young age, high-grade tumor, lymph node involvement)
• Tamoxifen alone can be considered but is less preferred due to inferior outcomes

For women with prior adjuvant therapy: 1

• Early relapse (≤12 months): Ovarian suppression + AI (nonsteroidal preferred)
• Late relapse (>12 months): Ovarian suppression + fulvestrant ± palbociclib, or ovarian suppression + AI + fulvestrant

Critical Monitoring Requirements

Estradiol monitoring with high-sensitivity assays is mandatory when using GnRH agonists with aromatase inhibitors. 1, 4

• Ovarian suppression may be incomplete, particularly when GnRH agonists are administered every 3 months (this schedule is not recommended). 1

• Target estradiol levels should be in the postmenopausal range (<26 pmol/L or <7 pg/mL) when using ovarian suppression plus AI. 4

• Serial assessment of luteinizing hormone, follicle-stimulating hormone, and estradiol is mandatory to ensure true postmenopausal status. 1

Methods of Ovarian Suppression

GnRH agonists and surgical oophorectomy achieve similar results in metastatic breast cancer. 1

• GnRH agonists (goserelin, leuprolide) are reversible options
• Surgical oophorectomy provides permanent suppression
• Both methods are acceptable; patient preference and fertility preservation goals should guide the choice 1

Common Pitfalls to Avoid

Do not assume chemotherapy-induced amenorrhea equals true menopause. 1, 4

• Women who become amenorrheic with chemotherapy may have continued estrogen production from the ovaries without menses
• Menopausal status cannot be determined while receiving ovarian suppression
• AI can stimulate ovarian function in premenopausal women, making this particularly dangerous 1

Do not use monthly GnRH agonist dosing schedules. 1

• Three-month dosing intervals are associated with incomplete ovarian suppression
• Monthly dosing provides more reliable estrogen suppression 1

Do not start AI without confirming adequate ovarian suppression. 1, 4

• Incomplete suppression leads to treatment failure and potential disease progression
• High-sensitivity estradiol assays must be used for monitoring 1, 4

Special Considerations

Fertility preservation should be discussed before initiating ovarian suppression. 1

• Options include cryopreservation of embryos or oocytes
• This discussion is critical given the loss of fertility with required systemic treatment 1

A balanced discussion of risks and benefits is mandatory, including potential side effects of premature menopause (vasomotor symptoms, bone loss, cardiovascular effects, sexual dysfunction). 1

If This Question Refers to Menopausal HRT (Not Cancer Treatment)

For healthy perimenopausal women considering HRT for symptom management, the approach is entirely different. However, the cardiovascular guidelines explicitly state that hormone therapy should not be initiated for cardiovascular disease prevention and carries increased risks in women with established cardiovascular disease. 1