Fibroid Treatments Demystified, Part V: Pharmacological Hormone Therapies

March 25, 2016

 

Uterine fibroids are almost always benign, but the debilitating symptoms experienced by an estimated 30% of women with fibroids can feel far from it. The nature and severity of fibroid symptoms depends on the size, and/or classification (submucosal, subserosal, intramural, or pedunculated) of the fibroids: common symptoms include abnormally heavy uterine bleeding, pelvic pain and bloating, abdominal pressure, urinary frequency, and constipation. A variety of surgical options are available to eliminate the tumors; for many women, however, the first step in addressing their condition is to seek relief of the symptoms through pharmacological treatments.

How Hormone Therapies Work

The majority of pharmacological products used to treat uterine fibroids do so by acting on the body’s hormonal balance. Research has shown that fibroid growth is fueled by hormones, specifically the hormones estrogen and progesterone. By directly or indirectly altering the levels of these hormones in the body, hormonal therapies can reduce the severity of fibroid symptoms like heavy bleeding and potentially shrink or inhibit the growth of fibroids. Approved hormonal therapies include GnRH agonists, oral contraceptives, progestins, aromatase inhibitors (AI), and other hormone-suppressing drugs like mifepristone.

Gonadotripin-releasing hormone agonists (GnRH-a) suppresses the body’s production of estrogen, creating a post-menopausal degree of estrogen deficiency. GnRH-a therapy has proven effective in both shrinking fibroids and managing symptoms like heavy bleeding. However, these effects are not sustained after discontinuing treatment. Use of GnRH agonists carries certain serious long-term health risks, including bone loss. Furthermore, because GnRH-a therapy essentially pushes the body into a menopausal state, women undergoing the treatment experience menopausal symptoms like hot flushes, vaginal dryness, weakness and fatigue, mood swings, and lowered libido. The negative effects of GnRH-a therapy can be countered by supplemental hormone treatments, but its associated health risks make GnRH agonists appropriate only for short term use, typically no longer than 6 months. Perhaps its most useful clinical application is rapidly shrinking large fibroids in preparation for surgical removal.

Oral contraceptives and progestins can be used for symptom relief, but their ability to reduce fibroid size is still uncertain. Studies have shown improvement in abnormal uterine bleeding with oral contraceptives. Drugs in this category, including lynestrenol, dienogest, and norethisterone, are considered relatively safe, and their low cost combined with potential benefit make them a promising choice for some women. However, women with pressure symptoms may not experience relief with oral contraceptives and progestins since they do little to shrink the fibroids or provide relief of bulk symptoms.

Aromatase inhibitors (AIs), part of a class of drugs known as anti-oestrogens, suppress the activity of the enzyme aromatase, which is responsible for the conversion of androgens into estrogens. Studies have suggested that use of AIs could inhibit fibroid growth and eliminate the need for surgery; however, further research has failed to provide sufficient evidence of this effect. Research surrounding the usefulness of AI’s in treating uterine fibroids continues, but in the meantime, the treatment is still considered experimental.

Mifepristone, a drug formerly known as RU486, belongs to a class of drugs known as progesterone receptor antagonists. As the category name implies, the drug acts on progesterone receptors. Mifepristone has proven effective in reducing uterine volume, thereby reducing blood loss and relieving related “bulk symptoms” like pelvic and lower back pain, abdominal pressure, and urinary frequency. The side effects of mifepristone are similar to GnRH-a therapy’s menopausal symptoms: hot flushes, mood swings, fatigue, and decreased libido are common, as well as headache, nausea, and diarrhea. In clinical trials, endometrial hyperplasia, a thickening of the uterine lining that creates a potential cancer risk, frequently resulted from mifepristone use. Due to a lack of data related to the safety outcomes of mifepristone use, the drug is not indicated for long-term use.

Comparing Pharmacological Treatment Options

How do these various hormonal therapies compare in terms of effectiveness? Comparative study data is still somewhat limited. One study compared the oral progestin lynestrenol with leuprolide, a GnRH agonist, and found no significant difference in their effectiveness for relieving pelvic pain and heavy bleeding. A separate, randomized clinical trial compared the GnRH agonist triptorelin with an aromatase inhibitor called letrozole, and revealed similarly significant decreases in fibroid volume (33% and 45%, respectively) with both therapies. In the latter study, however, none of the women treated with the aromatase inhibitor reported experiencing hot flushes, whereas 96% of the women taking a GnRH-a did. All of the approved hormonal therapies have shown some degree of effectiveness in treating fibroid-related symptoms; what determines their relative usefulness is predominantly the patient’s unique health history, as well as the nature and severity of each drug’s known side effects.

Limitations

While the available treatments vary in their mechanism for altering hormone levels, the hormonal therapies have a common limitation: they are not meant for long-term use. Clinical studies have consistently associated safety concerns with continued use of hormonal therapies in the treatment of fibroids. For many women, however, pharmacological treatments are an appropriate first step in addressing symptomatic fibroids. When symptoms persist and fibroids continue to impact a woman’s quality of life after trying a pharmacological treatment, a surgical approach would be an appropriate next step. For women concerned about the invasiveness of surgery, or the potential harm to the uterus that a procedure like hysterectomy entails, less invasive surgical options are worth consideration. Minimally invasive, uterine-sparing fibroid treatments like the Acessa Procedure offer a quicker recovery then major surgeries like hysterectomy, while providing the longstanding results that pharmacological therapies cannot.

 

SOURCES:
Levy, B. S. “Modern Management of Uterine Fibroids”, ACTA Obstetricia et Gynecologica, 2008, pp. 812-823

Song, H. et al. “Aromatase inhibitors for uterine fibroids”, Cochrane Database for Systematic Reviews/Cochrane Library, Oct 23, 2013. Web: http://onlinelibrary.wiley.com/enhanced/doi/10.1002/14651858.CD009505.pub2. Retr: Aug 1,2015

 

 

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