Continuous Use of Non-androgenic OC Improves Endometriosis Pain and Endometrioma Reoccurrence
Abstract & Commentary
By Michael A. Thomas, MD
Professor, Reproductive Endocrinology and Infertility; Director, Division of Reproductive Endocrinology and Infertility, University of Cincinnati College of Medicine
Dr. Thomas reports no financial relationships relevant to this field of study.
Synopsis: Compared to cyclic use, a drospirenone-containing oral contraceptive pill used in a continuous fashion after the removal of an endometrioma is associated with a reduction in dysmenorrhea, non-menstrual pelvic pain, and reoccurrence of endometrioma formation.
Source: Vlahos N, et al. Continuous versus cyclic use of oral contraceptives after surgery for symptomatic endometriosis: A prospective cohort study. Fertil Steril 2013;100:1337-1342.
In a prospective cohort trial at two different hospi-tals, 264 women underwent surgery for the treatment of pelvic pain and subsequently were diagnosed with endometriosis. The presence of endometriosis was documented and staged using the revised AFS/ASRM scoring criteria with patients divided into Stage I-II, Stage III, and Stage IV. Postoperatively, patients non-randomly selected a 6-month treatment course of an oral contraceptive pill (OCP) containing 3 mg drospirenone and 30 mcg ethinyl estradiol in a continuous (n = 96) vs cycle (21/7 day) fashion (n = 197). Eighty-five patients (88.5%) in the continuous arm and 167 (84.8%) in the cyclic arm completed the study. The baseline characteristics (age, parity, stage of AFS score, endometrioma bilaterality, endometrioma size, pre-op and immediate post-op pain symptoms of dysmenorrhea and dyspareunia) were comparable, except there was an increase in non-menstrual pain preoperatively in the continuous group (57.6% vs 41.9%, P = 0.023) and a trend toward the development of endometriomas in the continuous group (63.5% vs 50.3%, P = 0.06). After 6 months of treatment, the women taking the OCP in a continuous fashion demonstrated a greater reduction in dysmenorrhea (9.4% vs 23.9%, P = 0.021), non-menstrual pelvic pain (9.4% vs 23.9%, P = 0.0062), and recurrence of endometrioma (9.2% vs 16.6%, P = 0.025) than those taking the pill in the standard cycles. However, these continuous-use patients noted a higher percentage of breakthrough bleeding (23.5% vs 12.5%, P = 0.03) and higher rate of discontinuation (12.9% vs 8.3%, P = 0.037). Both OCP regimens decreased pain associated with dyspareunia. The authors concluded that the use of a continuous drospirenone-containing OCP regimen offers an improvement in endometriosis-related pelvic pain and reduction in endometrioma recurrence, but offers no additional benefit for dyspareunia.
COMMENTARY
Endometriosis is a common cause of pelvic pain in women in the reproductive age range. Although 10% of women are thought to have endometriosis, it is noted in 70% of those with pelvic pain.1-3 Women diagnosed with endometriosis usually present with complaints of dysmenorrhea, chronic non-menstrual pelvic pain, dysparenunia, and infertility.
Women with chronic pelvic pain without evidence of endometriosis can present with other gynecologic and non-gynecologic conditions that may mimic the same issues. Gynecologic problems that can cause pelvic pain include uterine fibroids, adenomyosis, pelvic adhesions, pelvic inflammatory disease, endosalpingiosis, congenital anomalies of the reproductive tract, and ovarian or tubal masses.4,5 Non-gynecologic disorders that may mimic or occur concurrently with endometriosis include irritable bowel syndrome, interstitial cystitis, fibromyalgia, and pelvic floor dysfunction. However, those with a true diagnosis of endometriosis are noted to have endometriotic lesions observed at the time of surgery (via laparoscopy or laparotomy) in and around the pelvic cavity that can be visualized as clear vesicles, red flame lesions, dark pigmented lesions, and/or white scarring of the peritoneum.
Although most agree that the most probable cause of development of endometriosis is retrograde menstruation (Sampson's theory),6 the mechanisms that initiate pain production are multifactorial. The three mechanisms agreed upon by most researchers are: 1) production of growth factors and cytokines by activated macrophages; 2) direct and indirect effects of active bleeding from endometriotic implants; and 3) irritation or direct invasion of pelvic floor nerves into the implants.5 If these mechanisms are an accurate cause of the pain associated with endometriosis, one or more mechanisms can occur at the same time, leading to chronic pelvic pain.
Although treatment options for patients with suspected endometriosis consist of surgical and non-surgical approaches, the current thought is to treat non-surgically first and foremost. If all medical options fail, then surgical intervention should be considered to diagnose and treat visualized endometriotic lesions. Not all implants are amenable to surgical treatment. Therefore, most agree that long-term, non-surgical treatment is necessary since endometriosis is a chronic condition that may not be optimally treated surgically.
OCPs are commonly used for the treatment of endometriosis. If the Sampson theory is true, every month, the peritoneal cavity is flushed with endometriotic cells through menstrual debris. The progestin in the OCP causes an induction of decidualization in eutopic and ectopic endometrial cells, which would include endometrial implants. Despite the fact that there are many options for postsurgical treatment (progestins only, danazol, GnRH agonist, and aromatase inhibitors), OCPs remain the most common treatment utilized by clinicians. Traditionally, an OCP with a more androgenic progestin, like the gonane levonorgestrel, was the first choice treatment selection for patients suspected to have endometriosis, but recent studies have demonstrated that the new generation of gonanes (desogestrel, norgestimate, and gestoden) work equally as well.7
In this study, patients underwent surgery for diagnostic purposes and then self-selected a continuous vs cyclic drospirenone-containing contraceptive pill regimen for treatment. Drospirenone is a 17-carbon progestin, but unlike its 19-carbon cousins, has no androgenic properties. Theoretically, you would suspect that the success of this compound would be questionable.
However, the patients who chose either the continuous or cyclic administration of this drospirenone agent showed a reduction in their postoperative endometrosis-associated pelvic pain symptoms. The greatest decrease in pain was in the group that selected the continuous regimen, which demonstrated a decrease in endometrioma formation and dysmenorrheal and non-menstrual pain. A drawback is the increase in breakthrough bleeding, but other studies show that this will improve with time in most users of continuous pills.8
Therefore, this study suggests that progestin effect alone of an OCP is more important than androgenicity when it comes to postoperative options for endometriosis. Also, when using a non-androgenic OCP compound, continuous administration offers an improvement in pain profile. Previous studies using the 19-nontestosterone agents usually showed no difference in continuous vs cyclic regimens.9 This study offers rethinking of an old dictum.
References
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- deHoop TA, et al. Endosalpingiosis and chronic pelvic pain. J Reprod Med 1997;42:613-616.
- Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril 2008;90(5 Suppl):S260-S269.
- Sampson J. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422-429.
- Vercellini P, et al. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril 2002;77:52-61.
- Archer DF, et al. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: Phase 3 study results. Contraception 2006;74:439-445.
- Seracchioli R, et al. Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis. Hum Reprod 2009;14:2729-2735.
