What is the relationship between Spironolactone (a potassium-sparing diuretic) and postmenopausal bleeding?

From the Guidelines

Spironolactone can cause postmenopausal bleeding as a side effect and requires prompt evaluation. If a postmenopausal woman on spironolactone experiences vaginal bleeding, she should immediately contact her healthcare provider for assessment, as this could indicate endometrial hyperplasia or cancer 1. The bleeding occurs because spironolactone has anti-androgenic properties that can affect the endometrial lining. Typical doses of spironolactone range from 25-100 mg daily, with higher doses increasing the risk of this side effect.

Key Considerations

• While on spironolactone, postmenopausal women should report any vaginal bleeding immediately, even spotting.
• Diagnostic evaluation typically includes a pelvic examination, transvaginal ultrasound to measure endometrial thickness, and possibly endometrial biopsy.
• Alternative medications like eplerenone might be considered if spironolactone is causing this issue, as eplerenone has less anti-androgenic activity 1.
• The risk of bleeding is higher in women with other risk factors for endometrial hyperplasia such as obesity, diabetes, or hypertension.

Management and Monitoring

• Potassium monitoring should be considered in older patients; patients with medical co-morbidities such as hypertension, diabetes mellitus, chronic kidney disease, among others; and patients taking medications affecting renal, adrenal, and hepatic function, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, digoxin, among others 1.
• Avoiding a diet high in potassium should be considered.
• Spironolactone should not be used in pregnancy, as it crosses the placenta and exposure in utero in animal studies may cause feminization of a male fetus 1.

From the Research

Postmenopausal Bleeding and Spironolactone

• Postmenopausal bleeding is an episode of bleeding 12 months or more after the last menstrual period, occurring in up to 10% of women aged over 55 years 2.
• The causes of postmenopausal bleeding include endometrial carcinoma, cervical carcinoma, vaginal atrophy, endometrial hyperplasia, cervical polyps, hormone-producing ovarian tumors, haematuria, and rectal bleeding 2.
• Spironolactone is a treatment for polycystic ovary syndrome (PCOS) and has been associated with menstrual abnormalities, including intermenstrual bleeding 3.
• In a study of PCOS patients with normal BMI, spironolactone treatment was found to reduce serum estradiol and endometrial thickness, with patients experiencing bleeding having significantly lower estradiol values than those without bleeding 3.

Diagnosis and Investigation of Postmenopausal Bleeding

• The aim of assessment and investigation of postmenopausal bleeding is to identify a cause and exclude cancer 2.
• Endometrial biopsy is a safe and efficient method to evaluate the endometrium for abnormal uterine bleeding and postmenopausal bleeding, with high specificity for diagnosing atypical hyperplasia and endometrial cancer in postmenopausal women 4.
• Ultrasound scan and endometrial biopsy are complementary, with ultrasound scan defining endometrial thickness and identifying structural abnormalities, and endometrial biopsy providing a histological diagnosis 2.
• The measurement of endometrial thickness aims to identify which women with postmenopausal bleeding are at significant risk of endometrial cancer, with a thickness of < 5 mm on transvaginal ultrasound scan indicating no further action is needed if the examination is normal and the bleeding has stopped 2.

Management of Postmenopausal Bleeding

• Menopausal hormone therapy (HT) is a common treatment for postmenopausal symptoms, but uterine bleeding is a common reason for discontinuation 5.
• The bleeding profile of HT varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations 5.
• Cumulative amenorrhea over a year ranges from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, with amenorrhea rates and the mean number of bleeding/spotting days improving over time 5.