Abstract
We treated four patients with severe abdominal pain in the luteal phase that showed a remarkable resemblance to dysmenorrhea. The symptoms began when the patients were in their twenties and thirties, and the pain was identical to the high phase of basal body temperature. No other abnormal findings were revealed in physical examinations, except for leiomyoma in two patients. Oral contraceptive use led to symptom exacerbation, while gonadotropin-releasing hormone agonist administration completely inhibited the pain. One patient underwent a hysterectomy for leiomyoma, with ovulation later confirmed, though luteal phase abdominal pain completely disappeared. Based on our findings, the postulated mechanism for the pain is uterine contractions induced by progesterone through various mechanisms. The symptoms in our patients were successfully treated by ovulation inhibition obtained with cyclic administration of conjugated estrogen.
Introduction
Dysmenorrhea, the most frequently encountered gynecologic disorder closely related to the menstrual cycle, is caused by uterine contractions due to prostaglandins contained in menstrual fluid, 1 while abdominal pain is also known as a partial manifestation of premenstrual syndrome (PMS), which shows various physical and psychological symptoms. 2
To the best of our knowledge, no previous report has noted such abdominal pain occurring in the luteal phase as a chief complaint. Here, we present details regarding four patients who complained of severe abdominal pain, with symptoms strikingly similar to dysmenorrhea in the luteal phase.
Case description
Case 1
The patient came to us at the age of 34. Age at menarche was 10 years and she had three normal vaginal deliveries at 18, 19, and 21 years, as well as two induced first trimester abortions. Following the last delivery at the age of 21, she began to be affected by abdominal pain from ovulation until the next menstruation, with cramps occurring in a 2-h cycle. The pain responded well to scopolamine-butylbromide. There were no other physical or mental symptoms, such as PMS.
At the first consultation at our hospital the patient was advised to record her basal body temperature (BBT) and those results showed that the abdominal pain was associated with a high phase of BBT. When oral contraceptives for inhibition of ovulation were administered, abdominal pain simultaneously began, while inhibition of ovulation with gonadotropin-releasing hormone analog (Gn-RHa) reduced abdominal pain. There was no pain relief with administration of conjugated estrogen (1.25 mg) from the fifth day of menstruation, because ovulation was not inhibited. However, an increase in the daily dose of conjugated estrogen to 2.5 mg successfully inhibited ovulation, resulting in freedom from abdominal pain. Thereafter, cyclic use of 2.5 mg of conjugated estrogen daily has been continued.
Case 2
The patient was first seen at our hospital at the age of 42. She married at the age of 23, and had two normal vaginal deliveries at the ages of 24 and 27, while menarche began at the age of 10 years. She had been diagnosed with a small uterine leiomyoma 10 years prior to the initial visit and also reported experiencing dysmenorrhea since she was young.
The patient suffered from luteal phase abdominal pain since the age of 32 years and the cramps were most severe for 3 days after BBT reached the high phase, for which she had received Gn-RHa therapy several times. There were no other physical or mental symptoms, such as PMS. Cyclic therapy with conjugated estrogen at 2.5 mg/day was given for luteal phase pain, which led to an anovulatory cycle and the pain stopped. Two years later, the patient underwent a total hysterectomy for treatment of uterine leimyoma tumors, which were revealed by a histological evaluation. Neither endometriosis nor adenomyosis was noted, and there were no other pathological findings. Following surgery, BBT recordings revealed recurrence of the ovulatory cycle, while cramps have not recurred.
Case 3
The patient married at 30 years, had a normal vaginal delivery at the age of 32, and then underwent laser surgery for severe dysplasia at the age of 33. Menstruation had always been painful since menarche at the age of 11 years, though the pain was reduced following delivery. Nevertheless, severe abdominal pain (visual analog score 10) developed during the luteal phase, which kept the patient from sleeping. The pain began from the 16th day of menstruation and stopped at the start of the next menstruation. Although various oral contraceptives were administered, the symptoms remained. She had no other physical or mental symptoms, such as PMS.
The patient first visited our hospital at the age of 38 and was advised to monitor BBT, which revealed that the abdominal pain was associated with the high phase. We prescribed conjugated estrogen at a dose of 2.5 mg daily, which successfully inhibited ovulation and resulted in freedom from abdominal pain. Thereafter, cyclic use of conjugated estrogen has been continued.
Case 4
The patient came to our hospital at the age of 35 with a history of primary infertility. Menarche was at 11 years old. She married at the age of 29 and underwent artificial insemination with her husband’s semen four times, but did not become pregnant. Under a diagnosis of suspected endometriosis, she was referred to our hospital for a laparoscopic evaluation.
Menstruation had been painful from the beginning and the patient reported severe abdominal pain during the luteal phase in addition to dysmenorrhea. Administration of a nonsteroidal anti-inflammatory drug (NSAID) had good effects on the dysmenorrhea, whereas luteal phase pain was severe and did not show such a response. Magnetic resonance imaging (MRI) findings revealed only uterine myoma. Inhibition of ovulation with Gn-RHa reduced the abdominal pain, while abdominal cramping recurred at the time of ovulation after finishing that therapy. Thereafter, the patient was given conjugated estrogen daily at 2.5 mg, which successfully inhibited ovulation, resulting in freedom from abdominal pain.
Discussion
We report here our experience with four patients with severe abdominal pain during the luteal phase. A physical disorder typically occurring during the luteal phase is PMS, which includes abdominal pain and the symptoms reported by the present patients could be considered to be partially related to PMS. However, according to the American College of Obstetricians and Gynecologists (ACOG), the defining criteria for diagnosis of PMS include at least one moderate to severe mood symptom and one physical symptom, 3 while the patients had no psychological symptoms and were only affected by abdominal pain. Therefore, we considered that the pain experienced by our patients was not a partial symptom of PMS.
Ovulation pain is well known to be related to the menstrual cycle. However, the pain reported by each patient in this study began at the same time as ovulation and then continued to just before the onset of the next menstruation. Thus, their pain was different from typical ovulation pain.
The symptoms were reported to be very severe and characteristically had a remarkable resemblance to dysmenorrhea. In the Case 3 patient, once menstruation began, the pain changed from luteal phase pain to dysmenorrhea. NSAID administration was effective for the dysmenorrhea, whereas the luteal phase pain was severe and that administration was not effective.
The pain experienced by each of our four patients could be characterized as follows:
The symptoms began at the age of 20–30 years.
The pain phase was identical to the high phase of BBT.
Pain severity was very strong and similar to dysmenorrhea.
Even when ovulation was inhibited by use of an oral contraceptive, the pain was not decreased but actually enhanced.
When ovulation was inhibited with Gn-RHa administration, the pain disappeared.
In a patient with the uterus removed and ovaries preserved, the pain stopped even though she showed ovulation.
No visible pelvic pathology findings, other than leiomyoma in two patients, were found in pelvic examination, MRI, and surgical results.
Based on these findings, the pain seems likely to have developed from an increase in the progesterone level after ovulation. However, in one patient who had her uterus removed, pain relief was obtained even though ovulation continued, thus the symptom may not be a direct action of progesterone, but rather an indirect action through the uterus. Since the pain in our patients showed a remarkable resemblance to dysmenorrhea, we speculate that it was caused by uterus contractions, the same as seen with primary dysmenorrhea. In other words, the pain noted in these cases can be considered as a condition that shows symptoms similar to primary dysmenorrhea during the luteal phase.
As for the cause of primary dysmenorrhea, increased uterine prostanoid production and release have been speculated. 4 In humans, progesterone opposes the effects of prostaglandins in the uterus during pregnancy, as well as in the luteal phase of the menstrual cycle by decreasing levels of the prostaglandins F2α and E in the endometrium. Furthermore, estrogen stimulation of prostaglandin F2α expression in the luteal phase of the cycle in the human endometrium is inhibited by progesterone. 5
Typically, severe abdominal pain due to uterine contractions is considered to be controlled by luteal progesterone release. However, this observation is in contrast to the traditional stance that endometrial prostaglandins are stimulated by estradiol and suppressed by progesterone. Although that initial concept was based on in vitro studies using endometrial cell and organ cultures, 5 as well as in vivo studies with rabbits, 6 the results provided scant evidence showing inhibitory effects of progesterone on uterine prostaglandins in humans or relevant animal models of human pregnancy, such as guinea pigs and nonhuman primates.7–9 In fact, examination of progesterone antagonists and the pure progestin R5020 in cyclic and pregnant guinea pigs have consistently demonstrated that progesterone is a potent stimulator of endometrial and myometrial prostaglandins in guinea pigs.7–9 Furthermore, the studies suggested that uterine prostaglandins are suppressed by placental or fetal factors, rather than progesterone, during pregnancy in primates and guinea pigs. In addition, effective termination of human pregnancy is only possible when a progesterone antagonist (e.g. mifepristone) is used in combination with a prostaglandin, which further opens to question the inhibitory effects of progesterone on uterine prostaglandins in humans. If progesterone actually induces uterine contractions, thus causing severe abdominal pain, the pathophysiology of the mechanism may not have been reported. We performed a search of PubMed using the keywords progesterone, uterine contraction, and abdominal pain, though no related reports were found.
Adequate inhibition of ovulation was easily obtained and was the most effective treatment for the present patients. However, oral contraceptives containing progestogen accelerated the pain and Gn-RHa should not be administrated for an extended period. Thus, we adopted a cyclic administration of conjugated estrogen at a dose of 2.5 mg/day along with low-dose aspirin as therapy. With that, ovulation was inhibited in all of the four patients and the symptoms completely disappeared without complications, resulting in relief from severe abdominal pain, leading to improved physical and psychological quality of life. Therefore, we propose the present treatment method for medical management of patients with this type of pain.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.