Dr. Ron’s Research Review – February 21, 2013

© 2013

This week’s research review focuses on abnormal uterine bleeding with HRT.

Continuous combined hormone therapy (HT) is effective for menopausal vasomotor symptoms and vaginal dryness but commonly leads to unscheduled vaginal bleeding and spotting. Nearly half of all continuous combined HT users make at least one visit to their gynecologist with unscheduled bleeding. Unscheduled bleeding is disliked by women and may lead to invasive investigations to exclude underlying pelvic pathology. In most cases investigations do not reveal any underlying cause for the bleeding. (Hickey, Ameratunga et al. 2011)

There is little consensus on who and when to investigate bleeding on HT, what to do about persistent bleeding and when re-investigation is indicated. A Pap smear should be obtained if a normal result has not been cited in the previous two years. Bleeding on continuous combined HT should be investigated if persistent for 6–9 months of use if new after a sustained period of amenorrhea or if heavy. Transvaginal ultrasound is useful. (Hickey, Ameratunga et al. 2011

Oral progesterone for 21 days per month and non-steroidal anti-inflammatory drugs are effective for the management of abnormal uterine bleeding in premenopausal women. (Sweet, Schmidt-Dalton et al. 2012)

Dr. Ron


Articles

Bleeding with menopausal hormone therapy

         (Hickey and Agarwal 2009) Download

Hormone therapy is highly effective for the treatment of menopausal vasomotor symptoms and vaginal dryness, but commonly leads to unscheduled vaginal bleeding and spotting. This frequently leads to invasive investigations to exclude underlying malignancy and is also very unpopular amongst users. In most cases, no pathology is found and the mechanisms underlying this irregular bleeding are poorly understood. Relatively few studies have investigated how combined hormone therapy might cause endometrial breakdown and bleeding. Evidence to date suggests that hormone therapy exposure induces changes in the density, distribution and structure of endometrial vessels, as well as alterations in the stroma, potentially leading to increased production of vasoactive mediators. The mechanisms of bleeding with menopausal hormone therapy seem to differ from those seen during normal menstruation and breakthrough bleeding in users of long-acting progestogen-only contraception.

Unscheduled bleeding in continuous combined hormone therapy users

         (Hickey, Ameratunga et al. 2011) Download

Continuous combined hormone therapy (HT) is effective for menopausal vasomotor symptoms and vaginal dryness but commonly leads to unscheduled vaginal bleeding and spotting. Unscheduled bleeding is disliked by women and may lead to invasive investigations to exclude underlying pelvic pathology. In most cases investigations do not reveal any underlying cause for the bleeding.


Evaluation and management of abnormal uterine bleeding in premenopausal women

         (Sweet, Schmidt-Dalton et al. 2012) Download

Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.


References

Hickey, M. and S. Agarwal (2009). "Bleeding with menopausal hormone therapy." Best Pract Res Clin Obstet Gynaecol 23(1): 141-9 PMID: 18977184

Hickey, M., D. Ameratunga, et al. (2011). "Unscheduled bleeding in continuous combined hormone therapy users." Maturitas 70(4): 400-3 PMID: 22030385

Sweet, M. G., T. A. Schmidt-Dalton, et al. (2012). "Evaluation and management of abnormal uterine bleeding in premenopausal women." Am Fam Physician 85(1): 35-43 PMID: 22230306