Uterine fibroids (aka leiomyomas) are a common benign uterine tumor that originates from the smooth muscle of the uterus. They are not cancerous growths. The incidence in general, in US women is about 9.6% of the female population, but it is more common in black women with an incidence of 18.5% (and possibly other nonwhite women). Approximately 25% to 50% of women with fibroids are symptomatic, experiencing heavy menses, reproductive issues, pain, increased urinary frequency, and anemia, and are more symptomatic in black women.
Uterine fibroids are the most common cause of gynecologic surgery worldwide yet still, the underlying cause remains unclear. More than 100 gene abnormalities are identified in leiomyomas involving the genes for hormone receptors, growth factors, extracellular matrix and collagen. The current factors that may be involved include: genetic factors, estrogen/progesterone receptors in the uterine muscle cells, growth factors such as insulin-like growth factor and extracellular matrix which is the material that makes cells stick together.
When we do not understand the cause of a medical condition, it makes it very hard to identify prevention and treatments. The current state of affairs offers 3 basic conventional options: 1) surgery (hysterectomy or myomectomy or hysteroscopic removal of intrauterine fibroids). The surgical options depend on fibroid location, size/mass of the fibroids, symptoms and other medical issues that might influence the best surgical option. 2) hormonal drugs that can temporarily shrink the fibroids prior to surgery; or, hormonal drugs that can improve some of the symptoms such as heavy bleeding 3) uterine artery embolization. In general, conventional medicine is left with insufficient non-invasive treatments where no pharmaceutical agent is known to shrink the fibroids in a long-term way.
The premise for N-acetyl cysteine (NAC) is as an antioxidant that inhibits free oxidative radicals and hopefully results in neutralizing the proliferation of uterine fibroid tumor cells. The hope is that the known antioxidant mechanism of NAC that reduces oxidative stress by inhibiting free radicals and glutathione synthesis, thus preventing the peroxidation of membrane lipids and preventing their release, may also lead to a reduction in uterine fibroid volume.
The current study is a randomized, double-blind controlled pilot study in Iran from 2017-2019. Selected candidates were women who were diagnosed with uterine leiomyoma based on transvaginal ultrasounds, and had a fibroid at least 8 cm or more, less than 4 uterine fibroids and just one type of fibroid (either submucosal, intramural or subserosal), with no pedunculated fibroids, were premenopausal, not pregnant, had not taken hormonal medications in the previous 6 months and no hormonal medication for their fibroids in the past 3 months and did not have certain diseases that were listed as exclusionary criteria. These women also had to have regular menstrual periods, onset of menses between ages 12 and 14, and had previously presented with heavy bleeding and painful periods.
A total of 50 women were accepted into the study with half being given NAC 600 mg/day for 3 months and the other half the placebo. Pelvic ultrasounds were performed before and after taking medication. No statistically significant difference was found between the two groups in terms of number and type of fibroids, and menopause status. The mean rates of volume reduction in group A (NAC group) were 25.25% and group B (placebo) was 1.08%. At the beginning of the study, heavy bleeding and painful menses were reported by women in both groups. The bleeding pattern changed during and after NAC treatment with a significant reduction in volume of bleeding and menstrual pain. There was also a significant reduction in fibroid and soft tissue tumor size in the treatment group. The average severity of pain in the NAC group was between 8 and 9 out of 10 before treatment and between 4 and 5 after treatment. Before NAC women had heavy bleeding and after, a pattern of moderate bleeding was reported.
Commentary: I am not sure of the fundamental logic for considering NAC for uterine fibroids. However, given that we have a significant lack of non-invasive treatment options, I’m certainly open to ideas and pilot studies. I also consider 600 mg/day of NAC to be a low dose when compared to the studies on polycystic ovary syndrome and endometriosis; although for endometriosis it was 600 mg three times daily for 3 days/week and for PCOS we usually see the studies at 500 mg three times daily. The study results lacked specificity for me… especially in it’s reported reduction in heavy bleeding, we do not know how many women improved and what defined heavy vs moderate. I can believe a reduction in symptoms after 3 months of any herbal or natural agent, but to reduce volume size within 3 month’s time is harder to believe. Believable or not, I will certainly try this non-invasive safe, natural therapy for my patients with non-pedunculated uterine fibroids with less than 4 fibroids. I will likely also not just limit my patients to those with a fibroid of at least 8 cm. There is only a small amount of other published research on natural agents, including green tea and black cohosh. While I will continue to make efforts with natural therapies to reduce bleeding and pain, to actually reduce size and number of fibroids has left me with very little optimism after 36 years of clinical practice. It is important for the woman with fibroids and her medical provider to recognize when it’s time for surgery or uterine artery embolization (UAE) and the benefits and risks of each kind of pelvic surgery or if UAE is a viable option.
Reference: Aghaamoo S, et al. The effect of N-acetyl cysteine on the volume of uterine leiomyoma: A randomized clinical trial. Int J Gynecol Obstet. 2021. 2021:00:1-5