# 20 - 405 Menstrual Disorders and Pelvic Pain

### 405 Menstrual Disorders and Pelvic Pain

Approximately 50% of girls with congenital hypogonadotropic hypo­
gonadism, with or without anosmia, have a history of some degree of 
breast development, and 10% report one to two episodes of vaginal 
bleeding. Family studies suggest that genes identified in association with 
absent puberty may also cause delayed puberty, and recent reports have 
further suggested that a genetic susceptibility to environmental stresses 
such as diet and exercise may account for at least some cases of func­
tional HA, including in girls who present with primary amenorrhea. 
Although neuroanatomic causes of delayed puberty are considerably 
less common in girls than in boys, it is always important to rule these 
out in the setting of primary hypogonadotropic hypogonadism.

PART 12
Endocrinology and Metabolism
■
■FURTHER READING
Balasubramanian R, Crowley WF Jr: Isolated gonadotropin-releasing 
hormone (GnRH) deficiency. 2007 May 23 [Updated 2022 May 12], in 
GeneReviews [Internet]. Adam MP et al (eds). Seattle, WA, University 
of Washington, Seattle, 1993-2025. Available from: https://www.ncbi.nlm.
nih.gov/books/NBK1334/.
Brito VN et al: The congenital and acquired mechanisms implicated in 
the etiology of central precocious puberty. Endocr Rev 44:193, 2023.
Cedars MI: Evaluation of female fertility-AMH and ovarian reserve 
testing. J Clin Endocrinol Metab 107:1510, 2022.
Lippincott MF et al: HU206 constitutional delay of puberty and 
idiopathic hypogonadotropic hypogonadism: differential contri­
butions of common genetic variants. J Clin Endocrinol Metab 
7:bvad114.1457, 2023.
Louden ED et al: Genetics of hypogonadotropic hypogonadism: 
Human and mouse genes, inheritance, oligogenicity, and genetic 
counseling. Mol Cell Endocrinol 534:111334, 2021.
Moore AM et al: KNDy neurons of the hypothalamus and their role 
in GnRH pulse generation: An update. Endocrinology 165:bqad194, 
2023. 
Janet E. Hall, Anuja Dokras

Menstrual Disorders 

and Pelvic Pain
Menstrual dysfunction can signal an underlying abnormality that may 
have long-term health consequences. Although frequent or prolonged 
bleeding usually prompts a woman to seek medical attention, infre­
quent or absent bleeding may seem less troubling, and the patient may 
not bring it to the attention of the physician. Thus, a focused menstrual 
history is a critical part of every encounter with a female patient. Pel­
vic pain is a common complaint that may relate to an abnormality of 
the reproductive organs but also may be of gastrointestinal, urinary 
tract, or musculoskeletal origin. Depending on its cause, pelvic pain 
may require urgent surgical attention. Recent guidelines no longer 
recommend routine pelvic examination in asymptomatic, average-risk 
women other than periodic cervical cancer screening. However, pelvic 
examination is an important part of the evaluation of amenorrhea, 
abnormal uterine bleeding, and pelvic pain.
MENSTRUAL DISORDERS
■
■DEFINITION AND PREVALENCE
Amenorrhea refers to the absence of menstrual periods and is classified 
as primary if menstrual bleeding has never occurred in the absence of 
hormonal treatment or secondary if menstrual periods cease for 
3–6 months. Primary amenorrhea is a rare disorder that occurs in 
<1% of the female population. However, between 3 and 5% of women 

experience at least 3 months of secondary amenorrhea in any specific 
year. There is no evidence that race or ethnicity influences the preva­
lence of amenorrhea. However, because of the importance of adequate 
nutrition for normal reproductive function, both the age at menarche 
and the prevalence of secondary amenorrhea vary significantly in dif­
ferent parts of the world.
Abnormal uterine bleeding (AUB) has replaced the term dysfunc­
tional uterine bleeding and describes irregularities in the menstrual 
cycle involving frequency, cyclicity, duration, and volume of flow out­
side of pregnancy. A menstrual cycle typically occurs every 21–35 days, 
lasting between 4 and 7 days, with up to 80 mL of blood loss. Variations 
in any of these parameters constitutes a diagnosis of AUB, with up to 
one-third of women between menarche and menopause experiencing 
these symptoms. The acronym PALM-COEIN, which was developed 
to describe the etiologies for AUB, includes the structural causes 
(polyp, adenomyosis, leiomyoma [submucosal or other myoma], and 
malignancy and hyperplasia) and nonstructural causes (coagulopathy, 
ovulatory dysfunction, endometrial, iatrogenic, and not yet classified). 
Oligo- and anovulation are most frequently associated with polycystic 
ovary syndrome (PCOS).
Primary Amenorrhea 
The absence of menarche (the first men­
strual period) by age 16 has been used traditionally to define primary 
amenorrhea. However, other factors, such as growth, secondary sexual 
characteristics, and the presence of cyclic pelvic pain, also influence 
the age at which primary amenorrhea should be investigated. Recent 
studies suggest that puberty is occurring at an earlier age, particularly 
in obese girls. However, it is important to note that these data reflect 
earlier breast development alone with minimal change in the age of 
menarche. Thus, an evaluation for amenorrhea should be initiated by 
age 15 or 16 in the presence of normal growth and secondary sexual 
characteristics; age 13 in the absence of secondary sexual character­
istics or if height is less than the third percentile; age 12 or 13 in the 
presence of breast development and cyclic pelvic pain; or within 2 years 
of breast development if menarche has not occurred.
Secondary Amenorrhea or Oligomenorrhea 
Irregular cycles 
are relatively common for up to 3 years after menarche and for 1–2 years 
before the final menstrual period. In the intervening years, menstrual 
cycle length is ~28 days. Cycle-to-cycle variability in an individual 
woman who is ovulating consistently is generally +/− 2 days. Pregnancy 
should be excluded early in any evaluation of menstrual irregularity. 
However, many women occasionally miss a single period. Three months 
of secondary amenorrhea, or 6 months in women with previously irreg­
ular cycles, should prompt an evaluation, as should a history of inter­
menstrual intervals >35 or <21 days or bleeding that persists for >7 days.
■
■DIAGNOSIS
Pregnancy is the most common cause of amenorrhea and must be 
excluded in all cases, regardless of patient history. Evaluation of men­
strual dysfunction depends on understanding the interrelationships 
between the four critical components of the reproductive tract: (1) 
the hypothalamus, (2) the pituitary, (3) the ovaries, and (4) the uterus 
and outflow tract (Fig. 405-1; Chap. 404). This system is maintained 
by complex negative and positive feedback loops involving the ovar­
ian steroids (estradiol and progesterone) and peptides (inhibin B and 
inhibin A) and the hypothalamic (gonadotropin-releasing hormone 
[GnRH]) and pituitary (follicle-stimulating hormone [FSH] and 
luteinizing hormone [LH]) components of this system (Fig. 405-1).
Disorders of menstrual function fall into two main categories: 
disorders of the uterus and outflow tract and disorders of ovulation. 
Many of the conditions that cause primary amenorrhea are congenital 
but go unrecognized until the time of normal puberty (e.g., genetic, 
chromosomal, and anatomic abnormalities). All causes of secondary 
amenorrhea also can cause primary amenorrhea.
Disorders of the Uterus or Outflow Tract 
Abnormalities of 
the uterus and outflow tract typically present as primary amenorrhea. 
In patients with normal pubertal development and a blind vagina,

–
GnRH
–
LH
FSH
+
Estradiol
Progesterone
FIGURE 405-1  Role of the hypothalamic-pituitary-gonadal axis in the etiology of amenorrhea. Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus 
stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion from the pituitary to induce ovarian folliculogenesis and steroidogenesis. Ovarian 
secretion of estradiol and progesterone controls the shedding of the endometrium, resulting in menses, and, in combination with the inhibins, provides feedback regulation 
of the hypothalamus and pituitary to control secretion of FSH and LH. The prevalence of amenorrhea resulting from abnormalities at each level of the reproductive system 
(hypothalamus, pituitary, ovary, uterus, and outflow tract) varies depending on whether amenorrhea is primary or secondary. PCOS, polycystic ovarian syndrome.
the differential diagnosis includes obstruction by a transverse vaginal 
septum or imperforate hymen; müllerian agenesis (Mayer-RokitanskyKuster-Hauser syndrome), which can be caused by mutations in the 
WNT4 gene, and androgen insensitivity syndrome (AIS), which is an 
X-linked recessive disorder that accounts for ~10% of all cases of pri­
mary amenorrhea (Chap. 403). Patients with AIS have a 46,XY karyo­
type, but because of the lack of androgen receptor responsiveness, those 
with complete AIS lack features of androgenization and have female 
external genitalia. The absence of pubic and axillary hair distinguishes 
them clinically from patients with müllerian agenesis, as does a testos­
terone level in the male range. The rare patient with 5α reductase type 
2 enzyme deficiency has a similar presentation but undergoes viriliza­
tion at the time of puberty. Asherman’s syndrome presents as secondary 
amenorrhea or hypomenorrhea and results from partial or complete 
obliteration of the uterine cavity by adhesions that prevent normal 
growth and shedding of the endometrium. Curettage performed for 
pregnancy complications accounts for >90% of cases; genital tuberculo­
sis is an important cause in regions where it is endemic.
TREATMENT
Disorders of the Uterus or Outflow Tract
Obstruction of the outflow tract usually presents as dysmenorrhea 
or lower abdominal cyclic pain with no menses. Evaluation of the 
patient includes a medical history, physical examination including 
a perineal examination, and ultrasound imaging. In many cases, a 
magnetic resonance imaging (MRI) scan can more accurately iden­
tify the reproductive tract anomaly prior to surgery. It is important 
that surgery be performed as soon as the diagnosis is made as 
the risk of endometriosis is increased with retrograde menstrual 
flow. Müllerian agenesis may require surgical intervention to allow 
sexual intercourse, although vaginal dilatation is adequate in some 
patients. In these patients, because ovarian function is normal, 
assisted reproductive techniques can be used with a surrogate 

Primary
Secondary
Hypothalamus
28%
36%
Menstrual Disorders and Pelvic Pain 
CHAPTER 405
Pituitary
2%
15%
Inhibin B
Inhibin A
Estradiol
PCOS
8%
30%
Ovary
43%
12%
Uterus/outflow tract
19%
7%
carrier. More recently, there have been a few cases of successful 
uterine transplantation in women with müllerian agenesis. AIS 
(Chap. 402) requires gonadectomy because there is risk of gonado­
blastoma in the dysgenetic gonads, although surgery is generally 
delayed until after breast development and the pubertal growth 
spurt. Estrogen replacement is indicated after gonadectomy, and 
vaginal dilatation may be required to allow sexual intercourse.
Disorders of Ovulation 
Once uterus and outflow tract abnor­
malities have been excluded, other causes of amenorrhea involve dis­
orders of ovulation. The differential diagnosis is based on the results 
of initial tests, including a pregnancy test, an FSH level (to determine 
whether the cause is likely to be ovarian or central), and assessment of 
hyperandrogenism (Fig. 405-2).
HYPOGONADOTROPIC HYPOGONADISM  Low estrogen levels in com­
bination with normal or low levels of LH and FSH are seen with 
anatomic, genetic, or functional abnormalities that interfere with hypo­
thalamic GnRH secretion or normal pituitary responsiveness to GnRH. 
Although relatively uncommon, tumors and infiltrative diseases should 
be considered in the differential diagnosis of hypogonadotropic hypo­
gonadism (Chap. 392). These disorders may present with primary 
or secondary amenorrhea. They may occur in association with other 
features suggestive of hypothalamic or pituitary dysfunction, such as 
short stature, diabetes insipidus, galactorrhea, and headache. Hypogo­
nadotropic hypogonadism also may be seen after cranial irradiation. 
In the postpartum period, amenorrhea occurs normally in association 
with breast feeding but may also be caused by pituitary necrosis (Shee­
han’s syndrome) or lymphocytic hypophysitis. Because reproductive 
dysfunction is commonly associated with hyperprolactinemia from 
neuroanatomic lesions or medications, prolactin should be measured 
in all patients with hypogonadotropic hypogonadism (Chap. 392).
Isolated hypogonadotropic hypogonadism (IHH) occurs in women, 
although it is three times more common in men. IHH generally pres­
ents with primary amenorrhea, although 50% have some degree of

Amenorrhea
uterus and outflow tract
Normal
Karyotype
+
β-hCG
Pregnancy
–
FSH
PART 12
Endocrinology and Metabolism
Normal/low
Normal
Hyperandrogenism
↑ testosterone
hirsutism, acne
Pituitary
causes
Hypothalamic
causes
R/o
• 21 hydroxylase
  deficiency
• Tumor
PCOS
FIGURE 405-2  Algorithm for evaluation of amenorrhea. β-hCG, β-human chorionic gonadotropin; FSH, follicle-stimulating hormone; GYN, gynecologist; MRI, magnetic 
resonance imaging; PRL, prolactin; R/O, rule out; TSH, thyroid-stimulating hormone.
breast development, and ~10% report one to two menses. IHH is asso­
ciated with anosmia in half of women (termed Kallmann’s syndrome). 
Genetic causes of IHH have been identified in ~50% of patients 
(Chaps. 403 and 404).
Functional hypothalamic amenorrhea (HA) is a diagnosis of exclu­
sion of other causes of hypogonadotropic hypogonadism including 
chronic diseases (type 1 diabetes, celiac disease, hyperthyroidism, 
Cushing’s syndrome) and use of opioids, glucocorticoids, or psychotro­
pic medications that increase prolactin levels. Functional HA is most 
commonly associated with conditions causing a mismatch between 
energy expenditure and energy intake and/or significant stress leading 
to increased corticotropin-releasing hormone (CRH), suppression of 
GnRH, and decreased thyrotropin-releasing hormone (TRH) input. 
Variants in genes associated with IHH may increase susceptibility to 
these environmental inputs, accounting in part for the clinical vari­
ability in this disorder. Metabolic and stress signaling is transduced 
to the reproductive axis, at least in part, through leptin signaling from 
the periphery and via hypothalamic kisspeptin, neurokinin B, and 
dynorphin control of GnRH. The diagnosis of HA generally can be 
made on the basis of a careful history, a physical examination, and the 
demonstration of low levels of gonadotropins and normal prolactin 
levels. Eating disorders, excessive exercise, and chronic disease must 
be specifically excluded. An atypical history, headache, signs of other 
hypothalamic dysfunction, or hyperprolactinemia, even if mild, neces­
sitates cranial MRI to exclude a neuroanatomic cause. Up to 10% of 
women with HA may have some features of PCOS (irregular menses, 
increased ovarian volume with polycystic appearing ovaries, higher 
anti-müllerian hormone [AMH] levels, and slightly elevated androgen 
levels).
HYPERGONADOTROPIC HYPOGONADISM  Ovarian failure is consid­
ered premature when it occurs in women <40 years old and accounts 
for ~10% of secondary amenorrhea. Primary ovarian insufficiency 
(POI) has replaced the terms premature menopause and premature 
ovarian failure in recognition of the continuum of impaired ovarian 

Abnormal
Normal
Abnormal
• High
 premature
 ovarian
 insufficiency
• Turner’s
 syndrome
• Androgen
  insensitivity
  syndrome
• 5α reductase
  deficiency
History of
uterine
instrumentation
• Müllerian
  agenesis
• Imperforate
  hymen
• Transverse
  vaginal
  septum
• Cervical
  stenosis
Normal prolactin
FSH negative
trial of estrogen/
progesterone
Asherman’s
syndrome
function encompassed by this disorder. Ovarian insufficiency is associ­
ated with the loss of negative feedback restraint on the hypothalamus 
and pituitary, resulting in increased FSH and LH levels. FSH is a better 
marker of ovarian failure because of loss of negative feedback effects of 
both estradiol and the inhibins and because its levels are less variable 
than those of LH. AMH levels will also be low in patients with POI. As 
with natural menopause, POI may wax and wane, and serial measure­
ments may be necessary to establish the diagnosis. The presentation 
may include irregular menses or complete cessation of menses, hot 
flashes, and vaginal dryness.
Once the diagnosis of POI has been established, further evaluation 
is indicated because of other health problems that may be associated 
with POI. Although POI is most commonly of unknown cause, it also 
occurs in association with a variety of chromosomal abnormalities 
(most often Turner’s syndrome), autoimmune polyglandular failure 
syndromes, and other rare disorders. Radiotherapy and chemotherapy 
may reduce ovarian reserve, with effects on both the oocytes and the 
supporting granulosa cells. New approaches, including ovarian, oocyte, 
and embryo cryopreservation, should be offered to women of repro­
ductive age prior to gonadotoxic chemotherapy or pelvic radiation 
treatment. The recognition that early ovarian insufficiency occurs in 
premutation carriers of the fragile X syndrome is important because of 
the increased risk of severe intellectual disability in male children with 
FMR1 mutations. Thus, follow-up testing should include a karyotype 
in all POI patients, serum anti-cortical and 21-hydroxylase antibodies 
(specific but not sensitive for subsequent adrenal insufficiency), thy­
roid function and thyroid peroxidase antibodies, FMR1 premutation 
screening, and assessment of bone mineral density. Ovarian biopsy is 
not indicated. Although the number of genetic causes of POI is increas­
ing, routine testing for mutations other than FMR1 is currently not 
recommended.
Hypergonadotropic hypogonadism occurs rarely in other disor­
ders, such as mutations in the FSH or LH receptors. Aromatase defi­
ciency and 17α-hydroxylase deficiency are associated with decreased 
estrogen and elevated gonadotropins and with hyperandrogenism and

hypertension, respectively. Gonadotropin-secreting tumors in women 
of reproductive age generally present with high, rather than low, 
estrogen levels and cause ovarian hyperstimulation or dysfunctional 
bleeding.
TREATMENT
Hypo- and Hypergonadotropic Causes of 
Amenorrhea
Amenorrhea almost always is associated with chronically low levels 
of estrogen, whether it is caused by hypogonadotropic hypogonad­
ism or ovarian insufficiency. Development of secondary sexual 
characteristics requires gradual titration of estradiol replacement 
with eventual addition of progestin. Hormone replacement with 
either low-dose estrogen/progesterone regimens or oral contracep­
tive pills is recommended until the usual age of menopause for 
bone and cardiovascular protection. In women with functional HA 
or anorexia nervosa, hormone replacement alone may not be suf­
ficient to restore or maintain bone density. A more long-term mul­
tidisciplinary approach including behavioral health professionals is 
essential. Patients with hypogonadotropic hypogonadism who are 
interested in fertility require treatment with both exogenous FSH 
and LH. Patients with POI can consider oocyte donation, which has 
a high rate of success in this population, although its use in women 
with Turner’s syndrome is limited by increased cardiovascular risk 
in pregnancy.
POLYCYSTIC OVARY SYNDROME  The diagnosis of PCOS is made in 
adult women using the updated Rotterdam criteria (published in the 
2023 international guidelines). These include irregular menses (<8 
menses per year), clinical or biochemical hyperandrogenism (elevated 
total or free testosterone, modified Ferriman-Gallwey score >4–6 
depending on ethnicity, see Chap. 406), and polycystic-appearing 
ovaries on ultrasound (≥20 antral follicles or ovarian volume ≥10 cm3 
in at least one ovary) or elevated AMH. The presence of two of the 
three criteria will confirm the diagnosis, resulting in different phe­
notypes, namely, hyperandrogenic or non-hyperandrogenic. PCOS 
is a diagnosis of exclusion, and other etiologies for irregular menses 
and hyperandrogenism should be excluded (hypothyroidism, hyper­
prolactinemia, adrenal sources for hyperandrogenism). Diagnosis in 
adolescents may be difficult to establish, and it is recommended to 
wait at least 3 years after menarche before confirming the diagnosis. 
In adolescents, the diagnosis is based on irregular menses and hyper­
androgenism criteria only, as the ultrasound and AMH criteria are 
not established for this age group. Lean oligo-ovulatory patients with 
PCOS generally have high LH levels in the presence of normal to low 
levels of FSH and estradiol, although given the pulsatility of LH secre­
tion, a random serum LH/FSH ratio is not included in the diagnostic 
criteria. The prevalence of obesity is high in PCOS and significantly 
increases the risk of comorbidities including metabolic syndrome, type 
2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. 
Frequent anovulation results in irregular menses and increased risk 
of endometrial hyperplasia and endometrial cancer (two- to sixfold 
increased risk). Abnormalities in GnRH pulsatility result in elevated 
LH levels resulting in increased production of ovarian androgens. 
Insulin resistance, especially in skeletal muscle and adipose tissue, 
also contributes to increased insulin-stimulated ovarian androgen 
production. An alternate source of androgens, namely 11-oxygenated 
androgens, may also be elevated in this population. Genome-wide 
association studies in diverse populations and PCOS phenotypes 
have identified several loci (~19) associated with PCOS, and cluster 
analyses suggest the presence of reproductive and metabolic abnor­
malities. Symptoms generally begin in adolescence and are modified 
by obesity and age, such that by the fourth decade of life, most women 
with PCOS will have regular menses and normal serum androgens. 
There is a high prevalence of depression and anxiety disorders, as well 
as disordered eating and body image distress. PCOS is also associ­
ated with an increased risk of obstructive sleep apnea and metabolic 

dysfunction-associated steatotic liver disease (MDSLD), independent 
of body mass index (BMI).

TREATMENT
Polycystic Ovary Syndrome
The first-line treatment of women with PCOS not attempting preg­
nancy is combined hormonal contraceptives to regulate menstrual 
cycles and decrease serum androgens by increasing sex hormone–
binding globulin levels. Although serum androgens decrease by 
2–3 months after initiating hormonal therapy, it may take longer 
to observe the beneficial effects on hirsutism and acne. Patients 
should be prescribed hormonal contraceptives containing the 
lowest effective dose of estrogen, either in a cyclic or continuous 
manner. If there is an inadequate response to hormonal con­
traceptives after 6 months for management of hyperandrogenic 
symptoms, antiandrogens, such as spironolactone and flutamide, 
can be considered (Chap. 406). Endometrial protection can also 
be achieved with the use of progestins (medroxyprogesterone 
acetate,10 mg, or Prometrium [progesterone], 200 mg daily 
for 10–14 days at least every 3 months, or a levonorgestrel 
intrauterine device [IUD]). All women with PCOS should be 
screened for obesity, hypertension, glycemic control, depression, 
and anxiety at the time of diagnosis and then at regular intervals. 
Overweight and obese women should also have a fasting lipid 
profile at the time of diagnosis. Lifestyle management should be 
recommended in all women with PCOS, and metformin should be 
considered for prevention of cardiometabolic risk factors in those 
with overweight and obesity (Chap. 420). Women with PCOS 
are at an increased risk of early miscarriage, gestational diabe­
tes, gestational hypertension, preeclampsia, and preterm birth. 
Lifestyle management and prepregnancy counseling should be 
offered prior to attempting pregnancy (Chap. 408). Letrozole, an 
aromatase inhibitor, is the first-line treatment for ovulation induc­
tion followed by clomiphene citrate, a selective estrogen response 
modulator, with or without metformin. Injectable gonadotropins 
can be used judiciously by experienced practitioners to induce 
monofollicular growth as PCOS increases the risk of hyperstimu­
lation. Metformin can be used as an adjunct with diet and exer­
cise for obese women with PCOS or for treatment of diabetes or 
impaired glucose tolerance, as in non-PCOS patients. However, 
metformin alone is not recommended for endometrial protection 
or treatment of hyperandrogenic symptoms, infertility, pregnancy 
loss, or prevention of gestational diabetes.
Menstrual Disorders and Pelvic Pain 
CHAPTER 405
■
■PELVIC PAIN
The mechanisms that cause pelvic pain are similar to those that cause 
abdominal pain (Chap. 16) and include inflammation of the parietal 
peritoneum, obstruction of hollow viscera, vascular disturbances, and 
pain originating in the abdominal wall. Pelvic pain may reflect pelvic 
disease per se but also may reflect extrapelvic disorders that refer pain 
to the pelvis. In up to 60% of cases, pelvic pain can be attributed to 
gastrointestinal problems, including appendicitis, cholecystitis, infec­
tions, intestinal obstruction, diverticulitis, and inflammatory bowel 
disease. Urinary tract and musculoskeletal disorders are also common 
causes of pelvic pain.
APPROACH TO THE PATIENT
Pelvic Pain
As with all types of abdominal pain, the first priority is to iden­
tify life-threatening conditions (shock, peritoneal signs) that may 
require emergent surgical management. The possibility of preg­
nancy should be identified as soon as possible by menstrual history 
and β-human chorionic gonadotropin (β-hCG) testing. A thorough 
history that includes the type, location, radiation, and recurrence 
can help identify the cause of acute pelvic pain. Specific associations

with vaginal bleeding, sexual activity, defecation, urination, move­
ment, or eating should be specifically sought. Determination of 
whether the pain is acute versus chronic and cyclic versus noncyclic 
will direct further investigation (Table 405-1). However, disorders 
that cause cyclic pain occasionally may cause noncyclic pain, and 
the converse is also true.
■
■ACUTE PELVIC PAIN
Pelvic inflammatory disease (PID) refers to infection of the upper geni­
tal tract and may present with a spectrum of symptoms. In the acute 
setting, the most common presentation is bilateral lower abdominal 
pain of recent onset that may be exacerbated with sexual activity. Risk 
factors for PID include age <25 years and history of multiple sexual 
partners, sexually transmitted infections (STIs), or recent uterine pro­
cedures. However, any sexually active woman can be at risk for PID. 
PID associated with tubo-ovarian abscess or peritonitis may present 
with severe pain, fever, and peritoneal signs. Abnormal uterine bleed­
ing may occur in about one-third of patients. Cervical motion tender­
ness, uterine and adnexal pain, and vaginal discharge are common 
findings on pelvic examination. The presence of right upper quadrant 
pain is suggestive of perihepatitis (Fitz-Hugh–Curtis syndrome).
PART 12
Endocrinology and Metabolism
The diagnosis of PID is established based on symptoms and clinical 
examination and can be aided by a wet mount preparation of vaginal 
discharge and nucleic acid amplification tests for Chlamydia trachomatis 
and Neisseria gonorrhoeae. Of note, a presumptive clinical diagnosis 
is sufficient to prescribe treatment even in the absence of positive test 
results, as PID can occur due to other vaginal and enteric pathogens. 
Pelvic imaging can be obtained based on symptoms, findings of the 
pelvic examination, or if there is lack of response to therapy. With 
public health efforts to control STIs, the incidence and severity of PID 
have declined in the United States and Europe; however, this is not the 
case in the developing world. Subclinical PID with its attendant risks of 
infertility and ectopic pregnancy remains a significant problem world­
wide. Public health and professional organizations recommend annual 
testing for C. trachomatis in all sexually active women <25 years old 
and both C. trachomatis and N. gonorrhoeae in all women at increased 
risk. Adnexal pathology can present acutely and may be due to rupture, 
bleeding, or torsion of ovarian cysts or, much less commonly, the fal­
lopian tubes. Rupture of an ovarian cyst may be diagnosed based on the 
acute presentation in a reproductive-age woman and pelvic ultrasound 
findings of a simple, collapsed or hemorrhagic cyst, with or without 
free fluid in the pelvis. Ovarian torsion typically presents as acute onset 
of unilateral, intermittent pain and is a diagnosis of exclusion unless 
absent blood flow to the ovary is demonstrated via Doppler ultrasound 
imaging. Neoplasms of the ovary or fallopian tube are much less com­
mon causes of acute pain.
Ectopic pregnancy represents 1–2% of all pregnancies and most 
commonly occurs in the fallopian tubes. It may present with acute 
lower abdominal pain, hemodynamic instability, and peritoneal signs. 
The index of suspicion should be high in any reproductive-age woman 
TABLE 405-1  Gynecologic Causes of Pelvic Pain
 
ACUTE
CHRONIC
Cyclic pelvic pain
 
Mittelschmerz
Dysmenorrhea
Noncyclic pelvic 
pain
Pelvic inflammatory 
disease
Ruptured or hemorrhagic 
ovarian cyst, 
endometrioma, or ovarian 
torsion
Ectopic pregnancy
Endometritis
Acute growth or 
degeneration of uterine 
myoma
Threatened abortion
Endometriosis
Uterine fibroids
Adenomyosis
Pelvic adhesions
Pelvic malignancy
Vulvodynia
Chronic pelvic inflammatory 
disease
Tuberculous salpingitis
History of sexual abuse
Pelvic congestion syndrome

presenting with abdominal pain or vaginal bleeding irrespective of cur­
rent use of contraception. Risk factors for an ectopic pregnancy include 
history of tubal disease, pelvic infection, tubal surgery, previous ectopic 
pregnancy, infertility, smoking, and current use of IUD, although a 
large proportion may have no risk factors. Rupture of the fallopian tube 
remains a life-threatening emergency; the incidence depends on access 
to care but is ~18% in developed countries. Diagnosis of an ectopic 
pregnancy can be established by assessing the patient’s menstrual his­
tory and symptoms, measuring a single or serial β-hCG levels, and 
performing pelvic ultrasound imaging. β-hCG levels typically double 
every 48 h in early first trimester, and 99% of viable intrauterine preg­
nancies are associated with an increase in hCG levels of at least 53% in 

2 days. The discriminatory zone refers to β-hCG values above which 
the landmarks of a normal intrauterine pregnancy should be seen on 
ultrasound (1500–3000 IU/mL). Absence of an intrauterine pregnancy 
and presence of an adnexal mass or free fluid increase the likelihood 
of an ectopic pregnancy. Threatened abortion may also present with 
amenorrhea, abdominal pain, and vaginal bleeding with no cervical 
dilation in the setting of an intrauterine pregnancy with cardiac activ­
ity in the first trimester of pregnancy. Although more common than 
ectopic pregnancy, it is rarely associated with systemic signs. Uterine 
pathology includes endometritis, and less frequently, degenerating leio­
myomas (fibroids) present with acute pain. Endometritis often is asso­
ciated with vaginal bleeding and systemic signs of infection. It occurs in 
the setting of STIs, uterine instrumentation, or postpartum infection.
TREATMENT
Acute Pelvic Pain
Treatment of acute pelvic pain depends on the suspected etiology 
but may require surgical or medical intervention. Immediate treat­
ment of PID is indicated upon diagnosis, even if the diagnosis is 
presumed or the symptoms are mild, due to long-term complica­
tions resulting in increased risk of ectopic pregnancy and infertility. 
Treatment in patients eligible for outpatient management includes 
250 mg IM ceftriaxone and a 14-day course of oral doxycycline 100 mg 
twice daily. If the presentation is acute with high fever, nausea, vom­
iting, severe abdominal pain, or presence of tubo-ovarian abscess, 
inpatient therapy is recommended (Chap. 141). Conservative man­
agement is an important consideration for ovarian cysts, if torsion 
is not suspected, to avoid unnecessary surgery and associated risks 
of reduced fertility due to cystectomy or adhesions. If surgery is 
performed, it is preferable to perform a cystectomy, removing the 
cyst wall and leaving the remaining ovary, in a reproductive-age 
woman. Combined hormonal contraceptives are recommended in 
women with a history of recurrent ovarian cyst formation. Surgi­
cal treatment may be required for ectopic pregnancies when the 
patient presents with acute pain, is hemodynamically unstable, or 
has signs of intraperitoneal bleeding. The choice of salpingectomy 
versus salpingostomy is based on patient’s presentation, desire for 
future child-bearing, and prior pelvic infections. Clinically stable 
women presenting with unruptured ectopic pregnancies may be 
appropriate for treatment with methotrexate, which is effective in 
~90% of cases when multiple doses are used. Threatened abortion 
is managed conservatively even in the presence of a subchorionic 
hemorrhage. The treatment of endometritis is similar to PID. Pain 
from a degenerating fibroid, if visualized on pelvic sonography, can 
be managed with nonsteroidal anti-inflammatory drugs (NSAIDs).
CHRONIC PELVIC PAIN
Chronic pelvic pain is a complex condition resulting from gyneco­
logic, urologic, or gastrointestinal organs and contributes to significant 
frustration and burden of disease. Common gynecologic conditions 
contributing to chronic pain are endometriosis, fibroids, adenomyosis, 
and adnexal pathology. In addition to a detailed history and physical 
exam, the evaluation of chronic pelvic pain typically includes a pelvic 
ultrasound. As causes other than those related to the female reproduc­
tive system are common, referral should be made to other specialists,