Treatment of symptomatic rectovaginal endometriosis with an estrogen–progestogen combination versus low-dose norethindrone acetate

doi:10.1016/j.fertnstert.2005.03.083

Fertility and Sterility

Volume 84, Issue 5, November 2005, Pages 1375-1387

https://doi.org/10.1016/j.fertnstert.2005.03.083 Get rights and content

Objective

To evaluate the efficacy, safety, and tolerability of an estrogen–progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis.

Design

Randomized controlled trial.

Setting

Academic center.

Patient(s)

Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis.

Intervention(s)

Twelve-month, continuous treatment with oral ethinyl E₂, 0.01 mg, plus cyproterone acetate, 3 mg/day, or norethindrone acetate, 2.5 mg/day.

Main Outcome Measure(s)

Degree of satisfaction with therapy.

Result(s)

Seven women in the ethinyl E₂ plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects (n=5), treatment inefficacy (n=6), or loss to follow-up (n=1). At 12 months, dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain, and dyschezia scores were substantially reduced without major between-group differences. Both regimens induced minor unfavorable variations in the serum lipid profile. According to an intention-to-treat analysis, 28 (62%) out of 45 patients in the ethinyl E₂ plus cyproterone acetate group and 33 (73%) out of 45 in the norethindrone acetate group were satisfied with the treatment received.

Conclusion(s)

Low-dose norethindrone acetate could be considered an effective, tolerable, and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception.

Section snippets

Materials and methods

This open-label, parallel-group, randomized, controlled trial compared a monophasic estrogen–progestogen combination containing cyproterone acetate with low-dose norethindrone acetate for the treatment of pelvic pain in women with persistent infiltrating rectovaginal endometriotic plaques after conservative surgery for symptomatic endometriosis. We studied 18-year to 35-year-old regularly menstruating women not wanting pregnancy, who had undergone laparoscopy or laparotomy for stage I to IV (18

Results

One hundred and thirteen women evaluated at our endometriosis outpatient clinic were eligible for the study, but 15 declined randomization and requested other treatment methods, and eight were lost to further contact. Forty-five of the remaining patients were allocated to the continuous ethinyl E₂ plus cyproterone acetate combination arm and 45 to the norethindrone acetate arm.

The baseline clinical characteristics of the women enrolled in the study are shown in Table 2. The distribution of the

Discussion

Rectovaginal endometriosis has been treated successfully with vaginal danazol (6), intramuscular depot GnRH analogues (7), and intrauterine progestins (10), but we are not aware of published reports on the use of oral progestogens or estrogen–progestogen combinations. Admittedly, progestogen treatments are symptomatic and do not cure deep-infiltrating disease (4). However, conservative surgery does not seem to be an optimal remedy for this condition as medium-term cumulative severe pain

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Pharmacology of endometriosis is the science of drugs prescribed for endometriosis, and their effects on the disease and the patient. This is a clinician’s essay on the pharmacology of the disease. A brief mention of the pathogenesis of the disease is included. Available treatment options for endometriosis associated pain are included, and those for infertility associated to endometriosis briefly described. Mechanism of action of drugs, and description of hormonal receptors are discussed. Treatments are introduced beginning with progesterone and progestogens, followed by hormonal contraceptives, GnRH agonists, GnRH antagonists, a brief historical review of past treatments (including antiprogestogens and androgens), hormone releasing intrauterine devices and implants, estrogen antagonists and aromatase inhibitors. Formulas are shown for all compounds, and comments on efficacy and side effects are included. The purpose of this article is to describe current treatments and help the clinician to make decisions when confronted with a patient complaining of pain and low quality of life due to endometriosis.
Advances in the medical management of bowel endometriosis
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Endometriosis infiltrating the bowel can be treated medically in accurately selected women not seeking conception and without overt obstructive symptomatology. When the rectosigmoid junction is involved, the probabilities of intestinal symptoms relief, undergoing surgery after treatment failure, and developing bowel obstruction during hormonal treatment are around 70%, 10%, and 1–2%, respectively. When the lesion infiltrates exclusively the mid-rectum, thus in cases of true rectovaginal endometriosis, the probabilities of intestinal symptoms relief and undergoing surgery are about 80% and 3%, respectively. Endometriotic obstructions of the rectal ampulla have not been reported. A rectosigmoidoscopy or colonoscopy should be performed systematically before starting medical therapies, also to rule out malignant tumours arising from the intestinal mucosa. Progestogens are safe, generally effective, well-tolerated, inexpensive, and should be considered as first-line medications for bowel endometriosis. Independently of symptom relief, intestinal lesions should be checked periodically to exclude nodule progression during hormonal treatment.
Tanshinone IIA contributes to the pathogenesis of endometriosis via renin angiotensin system by regulating the dorsal root ganglion axon sprouting
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Our study was designed to explore the function and mechanism of Tanshinone IIA in alleviating pain syndrome caused by endometriosis (EMs).
Female Sprague-Dawley rats went through autotransplantation operation to establish EMs model. The rats were randomly divided into five groups: sham, model, positive, Tanshinone IIA (L) (3 mg/kg/d) and Tanshinone IIA (H) (12 mg/kg/d) group. Volume of ectopic endometrium was measured after 21 days of continuous administration. Serum estradiol (E2) was detected by enzyme linked immunosorbent assay (Elisa). The protein expression of angiotensinogen (AGT), renin (REN), angiotensin converting enzyme (ACE), angiotensin II (ANGII) and angiotensin II type 2 receptor (AT2) in the dorsal root ganglion (DRG) neurons were measured by immunohistochemistry and Western Blotting. The mRNA expression levels of AGT and ANGII were measured by Real-time polymerase chain reaction (PCR).
Tissue measurements showed that tanshinone IIA significantly inhibited the growth of ectopic endometrium. Tanshinone IIA could improve the paw withdrawal threshold thus reducing the mechanical hyperalgesia of EMs rats. Moreover, Tanshinone IIA regulated the DRG renin angiotensin system (RAS) by reducing the protein expression of AGT, REN, ACE, ANGII and AT2 in DRG neurons. Furthermore, Real-time PCR results also showed that the mRNA expression levels of AGT and ANGII in the DRG neurons were decreased.
The Tanshinone IIA inhibitory effect on the EMs associated pain in EMs rats might occur through decreasing the expression of E2, ANGII and AT2, thus halting DRG sprouting and promoting hyperalgesia threshold.
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To compare the effects of Dienogest (D) and Norethindrone acetate (N) in symptomatic women with ovarian endometriomas, analyzing the efficacy in reducing endometrioma size and symptom relief and drug tolerability.
Retrospective study including 135 symptomatic women with ultrasonographic diagnosis of ovarian endometrioma. Women were divided into two groups: 1) women who received D 2 mg/day (group D); 2) women who received N 2.5 mg/day (group N). Women were evaluated at therapy prescription and after 6 and 12 months of treatment: transvaginal ultrasound was performed to assess the mean diameter of endometriomas, a Visual Analogue Scale was used to rank endometriosis related symptoms (dysmenorrhea, dyspareunia, chronic pelvic pain). The main outcome measure was the comparison between the 2 groups in terms of variations in endometrioma size and endometriosis related symptoms during the follow-up. Drug tolerability was also analyzed in terms of side effects.
A reduction in ovarian endometrioma size was observed during treatment in both groups, with no significant differences between groups D and N. Endometriosis related symptoms decreased in both groups, but the decrease was significantly higher in group D than in group N for all symptoms, both at 6 and 12 months of treatment. Regarding drug tolerability, uterine bleeding/spotting and weight gain were reported more frequently by women in the group N than women in the group D, both at 6 and 12 months of treatment.
Progestin therapy with D or N appears to be effective in reducing the size of endometriomas and related symptoms, with a greater effect on symptoms relief and higher tolerability in women treated with D.
Mechanical intestinal obstruction cause which mimic rectum tumor: Endometriosis
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Clinical and sonographic impact of oral contraception in patients with deep endometriosis and adenomyosis at 2 years of follow-up
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EndometriosisTreatment of symptomatic rectovaginal endometriosis with an estrogen–progestogen combination versus low-dose norethindrone acetate

Objective

Design

Setting

Patient(s)

Intervention(s)

Main Outcome Measure(s)

Result(s)

Conclusion(s)

Section snippets

Materials and methods

Results

Discussion

Fertil Steril

Am J Obstet Gynecol

Am J Obstet Gynecol

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Obstet Gynecol

Fertil Steril

Obstet Gynecol

Pain, quality of life and complications following the radical resection of rectovaginal endometriosis

BJOG

Deep endometriosisdefinition, pathogenesis, and clinical management

J Am Assoc Gynecol Laparosc

Endometriosis
Treatment of symptomatic rectovaginal endometriosis with an estrogen–progestogen combination versus low-dose norethindrone acetate