What is the role of female hormones, such as estrogen (E2) and progesterone (P4), in the female body?

Female Hormones: Roles and Functions

Primary Female Sex Hormones

Estrogen and progesterone are the primary female sex hormones that regulate reproductive function, cardiovascular health, bone density, and neurological processes throughout a woman's lifespan. 1, 2

Estrogen (Estradiol/E2)

Cardiovascular and Vascular Effects:

• Estrogen promotes vasodilation in peripheral vasculature and coronary arteries while inhibiting atherosclerosis development 1
• Reduces cardiomyocyte oxidative, ischemic, and hypertensive stress 1
• Reduces low-density lipoprotein cholesterol and increases high-density lipoprotein cholesterol 1
• Acts as a vasodilator through direct effects on blood vessel walls 1

Reproductive System:

• Increases approximately 50-fold during pregnancy, with estriol increasing by 1,000-fold 1
• Returns to prepregnancy levels within one to two weeks postpartum in non-breastfeeding women 1
• Remains suppressed during lactational amenorrhea in breastfeeding women 1
• Stimulates breast cell proliferation and inhibits apoptosis 1

Neurological Effects:

• Interacts with estrogen receptors in brain regions controlling reproductive behavior 1
• Mood disturbances are associated with sudden estrogen withdrawal, fluctuations, and sustained deficiencies—suggesting instability rather than absolute low levels drives mood effects 3
• Women with history of mood disorders show differential sensitivity to gonadal steroid fluctuations 3

Bone and Metabolic Effects:

• Cardioprotective at physiological levels in premenopausal women 1
• Lowering estrogen levels in aging women increases sodium sensitivity 1

Progesterone (P4)

Protective and Regulatory Functions:

• Increases approximately 10-fold during pregnancy 1
• Possesses anxiolytic and anesthetic properties 1
• Modulates serotonergic receptors 1
• Acts as protective against depression through its neurological effects 1

Metabolic and Vascular Effects:

• Promotes leptin-mediated endothelial dysfunction in obese premenopausal women through aldosterone and endothelial mineralocorticoid receptors 1
• May enhance sodium sensitivity in obese women 1

Reproductive Tissue Effects:

• Inhibits ovarian cancer cell growth and metastasis through suppression of epithelial-mesenchymal transition 4
• Dysregulated progesterone signaling contributes to endometriosis, adenomyosis, uterine fibroids, and polycystic ovary syndrome 5

Gonadotropins: LH and FSH

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate ovarian function and steroid hormone production, though robust reference intervals remain incomplete across the menstrual cycle. 2

Critical Clinical Considerations

Hormone Fluctuations vs. Absolute Levels:

• Individual sensitivity to hormone changes matters more than absolute hormone concentrations 3
• Women with pre-existing mood disorders require close monitoring during hormonal transitions 3
• The magnitude of hormonal decline does not predict mood outcomes; differential sensitivity determines who develops symptoms 3

Age-Related Changes:

• Over 40% of postmenopausal women develop hypertension, often poorly controlled 1
• The cardiovascular protective effects of estrogen diminish after menopause 1
• Pharmacological doses of estrogen in older women may have adverse vascular effects, contrasting with physiological benefits in younger women 1

Tissue-Specific Actions:

• Sex steroid hormones function through intracellular receptors (ER, PR, AR) that act as transcription factors 6
• Coregulators (coactivators and corepressors) modulate receptor function, and their aberrant expression contributes to cancer development 6

Common Clinical Pitfalls

Avoid assuming hormone therapy effects are uniform: Combined estrogen-progestin therapy shows different risk profiles than estrogen alone, with combined therapy increasing breast cancer risk while estrogen alone may slightly reduce it 1. The timing of administration (age at initiation, time since menopause) significantly affects cardiovascular outcomes 1.

Monitor for progesterone resistance: Imbalance between estrogen and progesterone leads to estrogen dominance and progesterone resistance, contributing to chronic pelvic pain, dysmenorrhea, heavy bleeding, and infertility 5.