Pocket ObGyn – Hormone Therapy

Pocket ObGyn – Hormone Therapy 
See Abbreviations

Definitions

• HT comprises estrogen & progesterone
• ET comprises solely estrogen
• “Timing hypothesis” – timing of initiation of HT in relation to chronologic age/length of menopause affect risk of primary endpoints (Am J Epidemiol 2007;166;511); secondary analysis of WHI/observational studies ® initiation of HT before 60 y of age or w/i 10 y of menopause may confer maximal cardioprotection for 6 or more years, improved QOL measures over 5–30 y (Climateric 2012;15(3):217).

Indications

• Principal indication for HT is rx of VS classified as mild, mod, or sev. FDA: Mod–sev VS is 8 hot flashes per day or 60 per week
• Use HT when benefits outweigh Benefit:risk ratio changes w/ age & w/ onset of menopausally related sx (eg,VS, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido, affecting QOL).
• “Timing hypothesis” implies benefits of short-term HT use for VS outweigh CV risk when initiation of HT occurs in close proximity to onset of menopause in appropriately selected pts (Hormone Therapy 2010;115(4):847).

Contraindications

• HT: H/o breast cancer, endometrial cancer, CHD, prev VTE or CVA, active liver dz, or high risk for these

Physical Exam

• Estrogen deficiency ® thin, pale vaginal mucosa, loss of elasticity & rugal folds, diminished secretions, shortened or narrowed vagina, moisture content ¯, the pH ­ (usually >5), & mucosal inflammation &

Assessment of the Risk–Benefit Ratio

• Women enrolled in WHI, a RCT w/ primary CV event had a mean age of 63–64 y &

>10 postmenopausal years.

• In a secondary analysis of WHI data ET arm, statistically signif reduction in CV endpoints (MI, coronary artery revascularization, & coronary death) in those aged 50–59.

 

Women’s Health Initiative (WHI): Main outcome of HT
Event	Relative risk (95% CI)	Increased absolute risk per 10 K/ person/y	Increased absolute benefit per 10 K persons/y
CV event(MI)	1.29	7
Stroke	1.41	8
TE	2.13	18
Breast cancer	1.26	8
Colorectal cancer	0.63		6
Hip fracture	0.66		5
Global index	1.15
From Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701–1712.

Treatment and Medications

• HT: Systemic ET is most effective rx for mod–sev VS; only therapy approved by the FDA for this indication (¯ 75% symptom).
• HT should be guided by use of smallest doses & shortest duration for symptomatic

 

Hormone therapy regimens
Low-dose combined regimens: 0.45 mg CEE/1.5 mg MDPA or 0.3 mg CEE/1.5 mg MDPA	In RCTs, low-dose combined regimens is as effective as high-dose combined std regimens
High-dose combined std regimen: 0.625 mg CEE/2.5 mg MDPA
Other formulations: Transdermal estradiol (E2) patches w/ std doses: 0.1 mg/d or 0.05 mg/d or lower doses: 0.025 mg/d, 0.014 mg/d Oral estradiol (E2): 0.5 mg/d or 1 mg/d Oral OCP for hot flushes in nonsmoking, healthy, perimenopausal women
Progesterone therapy: Medroxyprogesterone acetate 20 mg q orally or IM q3mo	Use when estrogen may be contraindicated & in all  w/ a uterus on ET
From Shifren JL, Schiff I. Role of hormone therapy in the management of menopause. Obstet Gynecol. 2010;115(4):839–855.

• Nonhormonal therapy as alternative in noncandidates for HT & mild VS: Lifestyle changes (reduction in body temperature, healthy wt maint, smoking cessation, relaxation techniques, acupuncture)
• Meds acting on central neurotransmitter pathways, decreasing central noradrenergic tone: Clonidine 1 mg weekly transdermal patch, (mainstay of nonhormonal therapy, but not FDA approved) paroxetine 10–20 mg/d or controlled release 12.5–25 mg/d, venlafaxine extended release 37.5–75 mg/d, gabapentin 300 mg/d to 300 mg TID.
• Duration of rx: Short-term therapy goal (£2–3 y) is symptomatic relief; annual reassessment of HT
• Discontinuation of rx: Abrupt withdrawal of exogenous estrogen ® return of hot flashes & other Based on WHI, ~55% recurrence w/ abrupt cessation. Estrogen

taper is not more effective than abrupt cessation. Limited trial data; if recurrent hot flashes w/ no resolution® nonhormonal medication. If ineffective, restart estrogen at the lowest dose poss (risk:benefit ratio) w/ plan to attempt discontinuation in the prox future.

• QOL: Whether HT improves HQOL is unk; data not available of effect of HT on global QOL (the sense of well-being w/ or w/o sx or physical impairments).

See Abbreviations