Predictors of breast discomfort among women initiating menopausal hormone therapy

Abstract

Objective-To study the determinants of breast discomfort among postmenopausal women initiating menopausal hormone therapy (HT).Methods-We analyzed questionnaire, anthropometric, and serum estrone data from the Postmenopausal Estrogen/Progestin Interventions Trial (PEPI), a randomized trial comparing placebo, conjugated equine estrogen (CEE) alone, or CEE with a progestogen (continuous or cyclical medroxyprogesterone acetate or cyclical micronized progesterone) among postmenopausal women. HT users could join PEPI after stopping HT for 2 months. We modeled the relation between smoking, body weight, alcohol consumption, age, quitting HT to join PEPI, physical activity and alpha-tocopherol consumption and new-onset breast discomfort at 12-month follow-up among 662 participants without baseline breast discomfort.Results-The associations of new-onset breast discomfort with weight and with strenuous exercise varied by treatment assignment. Among women assigned to CEE + progestogen, strenuous exercise was associated with a 49% lower odds of new-onset breast discomfort (OR 0.51, 95% CI 0.29-0.89, P = 0.02), whereas among women assigned to placebo or CEE alone, strenuous exercise was not significantly associated with new-onset breast discomfort. Surprisingly, among women taking CEE alone, each kilogram higher weight was associated with 6% lower odds of new-onset breast discomfort (P=0.04), whereas among women taking placebo, the association was in the opposite direction (P=0.04). Adjustment for estrone level had neglible effects on odds ratios. Alpha-tocopherol intake, age, smoking, and alcohol intake were not significantly associated with new-onset breast discomfort in adjusted analyses.Conclusion-Strenuous exercise and higher body weight may decrease the odds of new-onset breast discomfort among postmenopausal women initiating HT.

Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women’s health initiative clinical trials

“…Baseline hazard was stratified by age group (50–54, 55–59, 60–69, or 70–79 years-old) and randomization assignment in the WHI Dietary Modification Trial. We included the following variables based on biological plausibility and/or published studies: randomization assignment, age (linear), ethnicity (white, black, American Indian, Asian Pacific Islander, or unknown), alcohol consumption (nondrinker, ≤ 1 drink daily, or > 1 drink daily), cigarette smoking (never, past, or current), BMI (linear and quartiles), energy expenditure from physical activity (metabolic equivalent hours per week, including walking and mild, moderate, and strenuous physical activity, linear and quartiles), parity, age at first birth, breastfeeding (never, ≤1 year, > 1 year), time since menopause (<5 or 5–<10 or 10–<15 or ≥15 years), Gail model breast cancer risk (linear and quartiles), bilateral oophorectomy (yes/no), and menopausal hormone therapy use prior to trial participation (yes/no) [7,6,32–42,25,43–47]. …”

“…Although studies vary in timing and methods of assessment of breast tenderness during menopausal hormone therapy, the incidence of breast tenderness in double-blind randomized controlled trials ranges from approximately 8% to 15% after initiation of conjugated equine estrogen therapy (CEE) alone [1,2], and from 9%–16% after initiation of CEE combined with medroxyprogesterone acetate (MPA) [3,2,4–6]. Little is known about the predictors of new-onset breast tenderness during use of CEE-containing therapy [7]. Traditional clinical teaching considers menopausal hormone therapy-associated breast tenderness to be an annoying adverse effect that may resolve with cessation[8] or alteration of menopausal hormone therapy dose or preparation[9,10], but little attention has been given to the biology underlying, or the potential clinical relevance of, menopausal hormone therapy-associated breast tenderness.…”

A Mechanistic Review of Nicotine Toxicity with Recent Updates

“…The association between decreased fertility and smoking is not well known. Due to inhibition of aromatase enzyme activity by nicotine, the conversion of androgens into estrogens does not happen, so decreased level of estrogen and early onset of menopause in women are the results of nicotine exposure [179][180][181][182][183][184][185][186][187]. Nicotine disrupts the relationship between acetylcholine and its receptor and exerts its detrimental effects on placenta.…”