Yonago Acta medica 2013;56:81–84

Review Article: Special Contribution

Dysmenorrhea and Endometriosis in Young Women
Tasuku Harada
Division of Reproductive-Perinatal Medicine and Gynecologic Oncology, Department of Surgery, School of Medicine, Tottori University
Faculty of Medicine, Yonago 683-8504, Japan

ABSTRACT
Dysmenorrhea is defined as symptoms associated withmenstruation, such as abdominal pain, cramping andlumbago, that interfere with daily activity. Primary dysmenorrhea refers to menstrual pain without underlying
pathology, whereas secondary dysmenorrhea is menstrual pain associated with underlying pathology. Endometriosis, one of the main causes of secondary dysmenorrhea, induces dysmenorrhea, pelvic pain and infertility,
resulting in marked reduction of quality of life during
reproductive age. This review article is a comprehensive
overview of dysmenorrhea and endometriosis in young
women.

women of reproductive age.3 The main clinical features
are dysmennorhea, chronic pelvic pain and infertility.
Endometriosis is a chronic and recurrent disease that adversely affects quality of life in reproductive age women.
Sampson’s implantation theory, which describes
intraperitoneal menstrual reflux leading to spillage ofendometrial cells into the peritoneal cavity and the resulting development of endometrial lesions, is currently theprevailing explanation of the pathophysiology of endometriosis. Increased exposure to menstruation in terms ofshort menstrual cycles, prolonged flow and low parity are
possible risk factors.4 Therefore, retrograde menstruation
observed in 90% of menstruating women is considered a
key factor in the pathogenesis of endometriosis.
Incidence of endometriosis is believed to be increasing because of changes in women’s lifestyle, such as thetendency to marry later and have fewer children. This
life style change increases the number of times a woman
menstruates and affects the incidence of endometriosis.

Key words

adolescent; infertility; laparoscopic surgery; oral contraceptive; prostaglandin
Dysmenorrhea is defined as pathological symptoms associated with menstruation, marked by abdominal cramping and pain during the menstrual period that interferewith daily activity. Associated general symptoms, suchas nausea, vomiting, lumbago, diarrhea, and headache,
are also common. Dysmennorhea is categorized into two
types, primary and secondary. Primary dysmenorrhea
refers to menstrual pain without underlying pathology,
whereas secondary dysmenorrhea refers to painful menstruation associated with underlying pathology (Table 1).
One study, conducted with the support of the Japan
Ministry of Health and Welfare, revealed that menstrual
pain requiring pain medication occurs in 33% of menstruating Japanese women. In 6% of women, pain medications were ineffective and bedrest was needed. The
study results suggest that 1/3 of women who menstruate
may require medical intervention.1 Ikeda et al., reporting
the results of a questionnaire survey of menstrual pain
among high school students, revealed that 90.8% of students experienced menstrual pain and that pain affected
the daily activities of 51.8%. The incidence of menstrual
pain increased in 3rd grade students (17–18 years old)compared with 1st and 2nd grade.2
The most common cause of secondary dysmenorrhea
is endometriosis. Endometriosis is an estrogen-dependent
inflammatory disease characterized by ectopic growth ofendometrial stroma and glands affecting 5% to 15% of

MECHANISM OF (PRIMARY) DYSMENORRHEAThe etiology of primary dysmenorrhea includes an excess or imbalance in the amount of prostaglandins (PGs)
secretion from the endometrium during menstruation.
Associated general symptoms, such as nausea, vomiting,lumbago, diarrhea and headache are the sequel of influxof PGs and its derivatives into systemic circulation. Synthesis of arachidonic acids and the pathway of cyclooxygenase are activated by a decline of progesterone concentrations in the late secretory phase. PG levels in theendometrium of the late secretory phase increase 3 times
higher than those of the proliferative phase. A further
increase in PG levels is observed during the menstrualphase. PGE2 and PGF2 alpha concentrations are higher
in the menstrual fluid of women with dysmenorrhea thanin women with painless periods.5 Among PGs, PGF2a isconsidered the most potent causal factor of pain.
Corresponding author: Tasuku Harada MD, PhD
tasuku@med.tottori-u.ac.jp
Received 2013 September 20
Accepted 2013 September 20
Abbreviations: GnRH, gonadotropin-releasing hormone; LEP,
low dose estrogen-progestin; MRI, magnetic resonance imaging;
NSAID, nonsteroidal anti-inflammatory drug; OC, oral contraceptive; PG, prostaglandin81

T. Harada
Table 1. Differential diagnosis of primary and secondary dysmenorrhea
Primary
dysmenorrhea
Within 3 yr
after menarche
Age
15–25 yr old
Aging
Gradually improve
Marriage
Improve
Postpartum
Improve
Findings of internal		
Normalexamination
Onset

Time
Menstruation		
Duration
4–48 hgastrointestinal workup, were found to have peritoneal
endometriotic lesions as classified by American Societyof Reproductive Medicine. Laparoscopic resection orcautery of all visible lesions resulted in marked improvement of their pelvic pain.
Although Sampson’s theory of retrograde menstruation and implantation is believed to explain most casesof endometriosis, this theory clearly cannot explain
the cases of endometriosis in premenacheal girls whoneither menstruate nor have retrograde reflux. A recent
review by Brosens et al. suggested that endometriosis
may develop by mechanisms other than retrograde menstruation and implantation, such as coelomic metaplasia,
embryonic mullerian rests, or even the persistence ofthe forms of embryonic endometriosis recently described.12, 13 They also proposed that the phenomenon ofuterine bleeding in neonates and concomitant retrograde
menstruation in the neonate might be a source of stem
cells that develop into premenarcheal endometriosis.12
Therefore, it is suggested that premenarcheal and possibly adolescent endometriosis develop by activation ofresting stem cells shed at the time of neonatal retrograde
uterine bleeding.

Secondarydysmenorrhea
More than 5 yr
after menarche
Over 30 yr old
Become worse
No change
No change
Endometriosis,
fibroma, etc.
Menstruation orother time if worse
1–5 d

By preventing ovulation, oral contraceptives (OCs)suppress the progesterone-driven proliferation of thesecretory endometrium, resulting in a decrease in prostaglandin synthesis and volume of menstrual fluid.6
Consistent with Sampson’s theory, reduced menstrual
flow after taking OCs contributes to reduced retrograde
menstruation, which then impede the development ofendometriosis.
MECHANISM OF PAIN DUE TO ENDOMETRIOSISSYMPTOMS OF ENDOMETRIOSIS IN YOUNG WOMEN

Concentrations of PGs are higher in the menstrual bloodof women with endometriosis.7 Bulletti et al. found thatfrequency, amplitude and basal pressure tone of uterine
contractions in women with endometriosis were higher
than in those without.8 Thus, the severe dysmenorrhea
of endometriosis patients may be the result of abnormal
uterine contractions.
Endometriotic lesions and adhesions may also cause
the deep pelvic pain associated with endometriosis. Action mechanisms of pain with endometriosis are outlinedin Table 2. The pain of patients with endometriosis isthus due to both uterine contraction and endometriotic lesions.

Common symptoms in women with endometriosis include dysmenorrhea, lower abdominal pain and dyspareunia. Almost half of women with endometriosis also
report their inability to become pregnant. The pain ofendometriosis in adults is often cyclic while the presenting pelvic pain of adolescents can be either acyclic or
cyclic. Bowel and bladder symptoms commonly occur inadolescents (Table 3). The Endometriosis Association’s
1998 registry of 4,000 adult women with endometriosis
reported that 2/3 of those responding to the survey experienced their first pelvic symptoms before 20 years ofage, 21% before 15, and 17% between 15 to 19.14

ENDOMETRIOSIS IN YOUNG WOMEN

Table 2. Mechanism of pain associated with endometriosis

Retrospective studies report a diagnosis of endometriosis
in 25% to 38% of adolescents with chronic pelvic pain.9
Nonsteroidal anti-inflammatory drugs (NSAIDs) and oral
OCs are prescribed for adolescent patients with chronic
pelvic pain. If these agents are refractory, endometriosis
has been diagnosed in 50% to 70% of these patients.10
These results suggest that endometriosis should be partof the differential diagnosis of chronic pelvic or lower abdominal pain in premenarcheal and perimenarcheal girls.
While endometriosis usually occurs in women after
menarche, a series of 5 premenarcheal girls (ages 8.5
to 13 years) were reported to have endometriosis.11 The
girls, who all had chronic pelvic pain and a negative

A Pain due to endometriotic lesions
1 Peritoneal lesions induce inflammatory reactions and secrete
prostaglandins, cytokines, histamine and kinin that causepain.
2 Deep infiltrating endometriosis destroys tissues and nerves.
3 Ruptured chocolate cysts may irritate peritoneum.
B Scar and fibrosis, secondary lesions
1 Scar, fibrosis, traction, and adhesion may reduce mobility oforgans. Pain may occur during movement or ovulation.
2 Adhesion of bowel may cause defecation pain or dyschezia.
3 Retroverted uterus due to adhesion, severe adhesion of ovaries
to Douglas pouch, and induration of sacral ligament may cause
dyschezia.

82

Dysmenorrhea/endometriosis in the young
Table 3. Symptoms of endometriosis in young women
Symptoms

Frequency

Combination of cyclic and acyclic pain
Acyclic pain
Cyclic pain
Intestinal pain
Urinary symptoms
Irregular menstruation
Abnormal discharge

62.5%
28.1%
9.4%
34.3%
12.5%
9.4%
6.3%

Table 4. Red peritoneal lesions in young patients withendometriosis
		
NumberAge
Mean [SD]Patients with
red lesions

Young patients
LAVH

16.6 [1.4]
37.4 [3.4]

86%
20%

36
8

LAVH, laparoscopically assisted vaginal hysterectomy.
Data source: Davis et al., 1993.17

Data source: Laufer et al., 1997.10

examined 36 adolescent patients presenting with severe
dysmenorrhea who were refractory to prior therapy.
When compared with 46 women aged 31 to 46 years,
significantly more red lesions were present in adolescents (Table 4).
Demco examined endometriotic lesions using patient-assisted pelvic laparoscopy to determine color andsize and mapped these areas for pain.18 Of the lesions
that provoked a pain response, red, vascular lesions werethe most painful. This finding suggests that red lesions,most frequently observed in young patients with endometriosis, may be the cause of their pain.
Although, no correlation has been found between
severity of pain symptoms and stage of the disease orsite of the endometriotic lesions, laparoscopic resection
or cautery of the lesions improve symptoms in over 80%
of patients.
Clear lesions are common in adolescent endometriosis but are often difficult to visualize and evaluate
laparoscopically. Peritoneal defects or windows, which
are also diagnostic of endometriosis, are reportedly very
common in adolescents. Improved visualization andidentification can often be obtained by increasing thelaparoscopic magnification.19

DIAGNOSIS OF ENDOMETRIOSIS IN YOUNG WOMEN

Visual inspection by laparoscopy or laparotomy is thegold standard for diagnosing endometriosis. However,laparoscopy cannot always be performed in daily practicein Japan. Therefore, the term, “clinical endometriosis”, isused when only patient history, clinical examination andultrasound are available to support the diagnosis. Board
certified gynecologists can correctly diagnose endometriosis in 80% of the patients without laparoscopy.
Differential diagnosis is challenging in adolescents
because there can be coexisting diseases, including
those of the gastrointestinal system and urinary tract,pelvic inflammatory disease, ovarian cysts, obstructive
anomalies and pregnancy. The presenting symptoms canalso vary, ranging from only dysmenorrhea, localized
abdominal pain, dyspareunia, non-cyclic pain or combinations of these symptoms.
On examination, ovarian tumor and anomalies of
the genital tract must be ruled out. We perform transabdominal ultrasound examination while the patient hasa full bladder and rule out abnormalities in the uterus
and ovaries. We then inspect the genital area and vagina
and do a rectal examination if necessary. Magnetic resonance imaging (MRI) may also help to reveal an ovarian
tumor or anomalies.

CLINICAL MANAGEMENT OF ENDOMETRIOSIS IN
YOUNG WOMEN

Treatment of endometriosis may be surgical or medical. Surgical treatment, especially laparoscopic surgery,is the most effective method to control pain. Careful
history and examination is necessary to rule out pelvic
tumor or inflammatory disease. Young women with dysmenorrhea should be treated initially with a combinationof cyclic OCs and NSAIDs. In Japan, 2 cyclic OCs containing low dose estrogen-progestin (LEP) are coveredby national insurance.20 Side effects, such as nausea
and atypical bleeding, usually occur during the first 3
months of therapy, and patients should be advised about
this. If cyclic administration is not effective, the physician can recommend a continuous regimen of 3 to 4
months in which the patient takes the medication, disregarding any breakthrough bleeding. After laparoscopic
surgery for ovarian cysts, a continuous LEP regimen is

LAPAROSCOPIC FINDINGS IN ENDOMETRIOSIS IN
YOUNG WOMEN

Endometriotic lesions consist of a variety of types, including peritoneal implants, ovarian chocolate cysts,
adhesions, and deep infiltrated endometriosis. Ovarian
endometrioma is a common disease lesion occurring in
17% to 44% of endometriosis patients.15 However, thefinding is rare among adolescents and young women.
One review over a 15-year period reported no endometriomas among the ovarian masses found in 102 infants,
children and adolescents.16 Peritoneal endometriotic
lesions are categorized into 3 subgroups: red, black andwhite. Davis et al. reported that red lesions are the predominant implant type in adolescent patients.17 They83

T. Harada

more effective for pain and results in fewer recurring lesions after surgery for ovarian chocolate cysts.21
If pain persists with medical management, imaging,including ultrasound and MRI, may be ordered to evaluate endometriosis. Laparoscopy, the gold standard for
diagnosis, and laparoscopic excision of the lesions areusually effective for patients with severe pain symptoms.
Gonadotropin-releasing hormone (GnRH) agonist
therapy is widely used for adult patients, but it is not recommended as a first choice for young women because
the drug causes significant reduction in bone mineraldensity. A new progestin, dienogest, has been available
in Japan since 200822 and can be used for managementof pain associated with endometriosis in young women.
Dienogest has fewer side effects due to hypoestrogenand can be used for more than 1 year in adult patients.
Data are not available for GnRH agonist and dienogest
in an adolescent population. These agents may be introduced after establishing the diagnosis of endometriosis
by laparoscopy.

rophages in endometriosis. Prostaglandins. 1996;51:49-60.
PMID: 8900443.
8 Bulletti C, De Ziegler D, Polli V, Del ferro E, Palini S,
Flamigni C. Characteristics of uterine contractility during
menses in women with mild to moderate endometriosis. Fertile Steril. 2002;77:1156-61. PMID: 12057721.
9 Kontoravdis A, Hassan E, Hassiakos D, Botsis D, Kontoravdis
N, Creatsas G. Laparoscopic evaluation and management ofchronic pelvic pain during adolescence. Clin Exp Obstet Gynecol. 1999;26:76-7. PMID: 10459441.
10 Laufer MR, Goitein L, Bush M, Cramer DW, Emans SJ. Prevalence of endometriosis in adolescent women with chronic
pelvic pain not responding to conventional therapy. J Pediatr
Adolesc Gynecol. 1997:10:199-202. PMID: 9391902.
11 Marsh EE, Laufer MD. Endometriosis in premenarcheal girls
who do not have an associated obstructive anomaly. Fertile
Steril. 2005;83:758-60. PMID: 15749511.
12 Brosens I, Puttemans P, Benagiano G. Endometriosis: a life
cycle approach? Am J Obstet Gynecol. 2013;209:307-16.
PMID: 23500453.
13 Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M,
Baldi A. Ectopic endometrium in human fetuses is a common
event and sustains the theory of mullerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer. J
Exp Clin Cancer Res. 2009;28:49. PMID: 19358700.
14 Ballweg ML. Big picture of endometriosis helps provide guidance on approach to teens: comparative historical data show
endo starting younger, is more severe. J Pediatr Adolesc Gynecol. 2003;16:S21-6. PMID: 12742183.
15 Busacca M, Vignali M. Ovarian endometriosis: from pathogenesis to surgical treatment. Curr Opin Obstet Gynecol.
2003;15:321-6. PMID: 12858105.
16 Cass DL, Hawkins E, Brandt ML, Chintagumpala M, Bloss
RS, Milewicz AL, et al. Surgery for ovarian masses in infants,
children, and adolescents: 102 consecutive patients treatedin a 15-year period. J Pediatr Surg. 2001:36:693-9. PMID:
11329568.
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18 Demco L. Mapping the source and character of pain due toendometriosis by patient-assisted laparoscopy. J Am Assoc
Gynecol Laparosc. 1998;5:241-5. PMID: 9668144.
19 Laufer MR. Current approaches to optimizing the treatmentof endometriosis in adolescents. Gynecol Obstete Invest.
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20 Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa
N. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, doubleblind, randomized trial. Fertile Steril. 2008:90:1583-8. PMID:
18164001.
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2009;24:2729-35. PMID: 19625310.
22 Harada T, Momoeda M, Taketani Y, Aso T, Fukunaga M,
Hagino H, et al. Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated withendometriosis: a randomized, double-blind, multicenter, controlled trial. Fertile Steril. 2009:91:675-81. PMID: 18653184.

In summary, LEP and laparoscopic surgery are treatments of choice for young patients with endometriosis.
Endometriosis is a difficult disease to manage due to its
chronic and recurrent nature. Long-term management,with special attention to preservation of ovarian function,is highly important in treating young women with endometriosis.
The author declares no conflict of interest.
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