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The menstrual cycle and menstrual cycle abnormalities

Last updated: June 13, 2021

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The menstrual cycle is a highly regulated physiological process that makes conception and pregnancy possible. From the start of menstruation (menarche) to its cessation (menopause), menstrual bleeding (menses) is regulated by hypothalamic and pituitary hormones. Even the smallest changes in hormone levels can result in menstrual cycle abnormalities. Hormonal changes are not necessarily pathological; they can be caused by a variety of conditions and factors (e.g., medication, stress). Abnormal menstrual patterns are identified based on changes in the frequency, intensity, and onset of bleeding. Common manifestations of menstrual cycle abnormalities include amenorrhea (menstrual cessation), dysmenorrhea (painful menstruation), and abnormal uterine bleeding (AUB; e.g., increased frequency and/or volume of menstruation). Discomfort prior to the onset of menstruation that is accompanied by psychiatric, gastrointestinal, and/or neurological symptoms is referred to as premenstrual syndrome (PMS).

Hormonal feedback loops [1]

The menstrual cycle is a tightly regulated process in which the coordinated release of hormones from the hypothalamus, pituitary gland, and gonads produces a single mature oocyte. These hormones are controlled by positive and negative feedback loops.

The hormonal feedback loop is also influenced by other hormones (e.g., prolactin) and neurotransmitters (e.g., opioids, acetylcholine, noradrenaline). The feedback mechanisms are controlled by upregulating or downregulating hormone production as needed.

Menstrual cycle [1][2]

Menstrual cycle changes
Cycle Duration Phases Description Mechanism Histological changes [2]
Ovarian cycle
  • 1–14 days
  • Follicular phase
  • From the first day of menses to the day before the LH surge
  • Accounts for most of the variability in the length of the menstrual cycle
  • Follicle growth speeds up during the 2nd week of this phase.
  • 14–15 days
  • Luteal phase
Uterine cycle
  • 3–7 days
  • Menses
  • Menstrual bleeding occurs in this phase (usually 14 days after ovulation).
  • ∼10 days
  • Proliferative phase
  • 10–14 days
  • Secretory phase

Menstrual cycle abnormalities include changes in the frequency and intensity of menstruation as well as symptoms such as pronounced abdominal discomfort, gastrointestinal complaints, and/or psychiatric symptoms.

Primary dysmenorrhea

Secondary dysmenorrhea [5][7]

Primary amenorrhea [8][9]

Causes of primary amenorrhea
Cause Details GnRH FSH and LH Estrogen and progesterone
Constitutional
growth delay
  • ↓ (at the prepubertal level)
Hypogonadotropic
hypogonadism
  • Normal or ↓
Hypergonadotropic
hypogonadism
Anatomic anomalies
  • Normal
  • Normal
  • Normal
Receptor and enzyme abnormalities
  • Normal
  • Normal or ↑
  • Normal or ↓

Secondary amenorrhea

Physiological amenorrhea occurs before menarche, after menopause, during pregnancy, and during lactation.

The female athlete triad of functional hypothalamic amenorrhea: low calorie intake/strenuous physical activity, low bone mineral density, and amenorrhea

Characteristics and causes of AUB according to FIGO [12]
Characteristic Normal parameters Abnormal parameters Common causes

Frequency

  • ≥ 24–38 days
  • Infrequent: cycles intervals > 38 days
  • Frequent: cycles intervals < 24 days

Regularity

  • Variation between shortest and longest cycle 7–9 days or normal cycle length ± 4 days
  • Irregular
    • Variation between shortest and longest cycle ≥ 8–10 days (the amount of variation considered normal depends on the individual)

Duration

  • ≤ 8 days
  • Prolonged: > 8 days

Volume

  • Determined by the patient
  • Heavy menstrual bleeding: excessive blood loss that interferes with physical, social, and/or emotional quality of life
Intermenstrual bleeding
  • None
  • Random
  • Cyclic (predictable bleeding): minimal bleeding seen during early, mid, or late cycle

In patients with acute abnormal uterine bleeding and onset of menarche within the last year, anovulatory bleeding due to immaturity of the hypothalamic-pituitary-gonadal axis should be considered.

  • Epidemiology
    • Occurs in up to 12% of female individuals [15]
    • Age of onset: 20–30 years of age [15]
  • Clinical features [15][16]
  • Diagnostics [16]
Premenstrual syndrome (PMS) Premenstrual dysphoric disorder (PMDD)
Definition
  • The onset of severe discomfort or functional impairment prior to menstruation
  • Severe affective symptoms and behavioral changes that cause clinically significant disturbance of daily life
Diagnostic criteria
  • Present in the 5 days prior to the beginning of menstruation for at least 3 consecutive cycles
  • End within 4 days after the beginning of menstruation
  • Interfere with normal daily life activities
  • Present up to 7 days prior to the onset of menstruation for the majority of cycles within one year
  • ≥ 5 symptoms that are marked and/or persistent (e.g., depressed mood, anxiety, anger, affective lability, sleep disturbances, change in appetite, pain, headache)
  • Significant interference in daily life (work, home, social activities, interpersonal relationships)
  • Definition
    • Physiological preovulatory pain in female individuals of reproductive age
    • Also referred to as ovulatory or midcycle pain
  • Epidemiology: occurs in approx. 40% of female individuals of reproductive age [18]
  • Etiology: Enlargement and rupture of the follicular cyst and contraction of Fallopian tubes during midcycle ovulation lead to transient peritoneal irritation from follicular fluid. [1]
  • Clinical features
  • Management: symptomatic treatment with NSAIDs as needed
Differential diagnosis and treatment of dysmenorrhea and AUB
Condition Clinical features Diagnostics Treatments
Primary dysmenorrhea
  • Spasmodic, crampy pain in the lower abdominal and/or pelvic midline
  • Diagnosis of exclusion
Endometriosis
Adenomyosis
Endometritis
  • Mild to moderate cases (outpatient treatment)
    • One single dose of IM ceftriaxone and oral therapy with doxycycline
    • Addition of metronidazole should be considered in some cases (e.g., patients who recently underwent gynecological procedures).
  • Severe cases (inpatient treatment): clindamycin PLUS gentamicin
Endometrial carcinoma/hyperplasia
Uterine leiomyoma
  • Ultrasound (best initial test)
  • MRI to evaluate surgical options and differential diagnoses
Endometrial polyps
  • Often asymptomatic
  • AUB
  • Infertility/difficulty conceiving
  • Incidental finding
  • Asymptomatic: observation and follow-up
  • Symptomatic: surgical removal
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