Does estrogen therapy help manage hypertension?

Estrogen's Effects on Blood Pressure

Estrogen therapy generally does not help with blood pressure management and may actually increase blood pressure in some formulations, particularly oral contraceptives and conjugated equine estrogens. 1, 2

Different Forms of Estrogen and Their Effects on Blood Pressure

Oral Contraceptives

• Oral contraceptives containing ethinyl estradiol typically cause a small but detectable increase in blood pressure 1
• Higher doses of ethinyl estradiol (>50 mcg) are associated with a 6/3 mmHg increase in blood pressure 1
• Women with significant hypertension should not be started on hormonal contraception 2
• The FDA label clearly states that elevated blood pressure has been reported in women taking oral contraceptives, with higher risk in:
  • Older users
  • Extended duration of use
  • Formulations with higher progestational activity 2

Postmenopausal Hormone Therapy

• Results from studies on postmenopausal hormone therapy are inconsistent 1, 3, 4
• The Women's Health Initiative (WHI) found an average 1 mmHg increase in systolic blood pressure over 5.6 years with conjugated equine estrogen plus medroxyprogesterone 1
• Current hormone use was associated with a 25% greater likelihood of having hypertension compared to past use or no prior use 1
• Route of administration matters:
  • Oral estrogen was associated with a 14% higher risk of hypertension compared to transdermal estrogen 3
  • Conjugated equine estrogen was associated with an 8% increased risk of hypertension compared to estradiol 3, 4

Formulation-Specific Effects

Beneficial or Neutral Effects

• Transdermal estrogen and micronized progesterone had a beneficial effect on blood pressure in normotensive women and a neutral effect in hypertensive women 5
• Drospirenone (a newer progestin) may actually decrease blood pressure in some users due to its anti-mineralocorticoid effects 1, 6
• Natural estrogens (estradiol valerate, estetrol) combined with newer progestins show minimal effects on blood pressure:
  • Estetrol 15mg/drospirenone 3mg was not associated with changes in BP after 13 cycles 1
  • Estradiol valerate/dienogest showed no significant changes in BP after 6 months 1

Harmful Effects

• Oral conjugated equine estrogens plus progestogen increased systolic blood pressure (0.60 mmHg) and the risk of hypertension 4
• Duration of estrogen exposure and cumulative dose are positively associated with risk of hypertension 3

Pathophysiological Mechanisms

• Estrogen stimulates hepatic production of angiotensinogen leading to renin-angiotensin-aldosterone system (RAAS) activation 1
• This effect appears to be dose-dependent:
  • Plasma angiotensinogen levels doubled with ethinyl estradiol 50mcg
  • Levels increased by only 12-20% with ethinyl estradiol 30-35mcg 1
• Estrogen may impair feedback inhibition of RAAS, leading to higher plasma renin concentration 1
• Physiological levels of estrogen are cardioprotective and promote vasodilation, but pharmacological doses may have adverse effects 1

Recommendations for Clinical Practice

• For women requiring contraception or hormone therapy who have hypertension or are at risk:

  • Choose non-oral routes of administration (transdermal, vaginal) when possible 3
  • Prefer estradiol over conjugated equine estrogens 3, 4
  • Consider formulations with drospirenone if oral administration is necessary 1, 6
  • Use the lowest effective dose for the shortest time period 3
  • Monitor blood pressure closely, especially during the first 6 months of therapy 1, 2

• For women already on estrogen therapy:

  • If significant blood pressure elevation occurs, discontinue the therapy 2
  • For most women, elevated blood pressure will return to normal after stopping oral contraceptives 2

Important Caveats

• Individual responses to estrogen therapy vary considerably
• Women with pre-existing hypertension are at higher risk for further blood pressure elevation
• The blood pressure effects of estrogen therapy should be weighed against its benefits for treating menopausal symptoms or providing contraception
• Larger trials powered to detect differences in blood pressure between different formulations are still needed 1