Overview
Definition:
Amenorrhea refers to the absence of menstruation
When a patient using oral contraceptive pills (OCPs) experiences amenorrhea, it can be due to a contraceptive-induced effect (breakthrough bleeding or withdrawal bleeding cessation) or, more critically, pregnancy
An endocrine workup is crucial to differentiate these possibilities and identify underlying hormonal imbalances.
Epidemiology:
The incidence of amenorrhea in OCP users is variable
While many users experience predictable withdrawal bleeding, a significant proportion may experience amenorrhea, especially with continuous or extended-cycle regimens
The risk of pregnancy in correctly used OCPs is very low (<1%), but non-adherence increases this risk substantially
Endocrine causes of amenorrhea are common in adolescent females, making them relevant in this context.
Clinical Significance:
Amenorrhea on OCPs, particularly if it represents pregnancy, has significant implications for adolescent reproductive health, maternal care, and potential teratogenic risks if the pregnancy continues unaware
Identifying underlying endocrine disorders is vital for long-term health management, bone health, and fertility.
Clinical Presentation
Symptoms:
Absence of expected withdrawal bleeding (in cyclic OCP users)
Missed period with contraceptive pill use
Symptoms suggestive of pregnancy: nausea, vomiting, breast tenderness, fatigue
History of inconsistent OCP use or missed pills
Abdominal pain may suggest ectopic pregnancy if pregnancy is confirmed
Symptoms of underlying endocrine disorders: hirsutism, acne, galactorrhea, rapid weight gain/loss, significant mood changes.
Signs:
Uterine size may be normal or enlarged if pregnant
Pelvic examination may reveal cervical changes if pregnant
Signs of hormonal imbalance: acne, hirsutism, acanthosis nigricans, galactorrhea, breast development abnormalities
Vital signs should be assessed for stability, especially if significant bleeding or suspected ectopic pregnancy.
Diagnostic Criteria:
Diagnosis of amenorrhea is clinical: absence of menses for at least 3 cycles in a woman who previously had regular cycles, or for 6 months in adolescents with primary amenorrhea or those with established menstrual cycles
Confirmation of pregnancy via a sensitive human chorionic gonadotropin (hCG) assay is paramount.
Diagnostic Approach
History Taking:
Detailed menstrual history prior to OCP use
Type of OCP used and adherence patterns (missed pills, timing)
Sexual activity and contraceptive practices
Recent changes in OCP formulation or dosage
Symptoms of pregnancy
Family history of endocrine or reproductive disorders
History of significant weight changes, excessive exercise, or stress
Review of medications and comorbidities.
Physical Examination:
General physical examination: assessment of growth parameters (height, weight, BMI), signs of systemic illness
Endocrine assessment: signs of hyperandrogenism (hirsutism, acne, clitoromegaly), thyroid examination, breast examination for galactorrhea, assessment of pubertal development (Tanner staging)
Pelvic examination: assessment of external genitalia, vagina, cervix, uterus, and adnexa
Assess for anatomical abnormalities.
Investigations:
Urine or serum hCG: The primary investigation to rule out pregnancy
If hCG is positive, management proceeds as per pregnancy guidelines
If hCG is negative and amenorrhea persists: Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2) levels to assess ovarian function and hypothalamic-pituitary axis
Thyroid-Stimulating Hormone (TSH): to rule out thyroid dysfunction
Prolactin levels: to assess for hyperprolactinemia
Androgen levels (testosterone, DHEAS): if hirsutism or PCOS suspected
Progesterone challenge test: may be used to assess estrogenization and uterine responsiveness
Pelvic ultrasound: to visualize uterus, ovaries, and assess for anatomical abnormalities, ovarian cysts, or signs of PCOS
Consider karyotyping if primary amenorrhea and suspected gonadal dysgenesis.
Differential Diagnosis:
Pregnancy: The most critical diagnosis to exclude
OCP-induced amenorrhea: common, especially with continuous use
Polycystic Ovary Syndrome (PCOS): common endocrine cause of menstrual irregularities
Hyperprolactinemia: can suppress ovulation and menstruation
Hypothalamic amenorrhea: due to stress, weight loss, excessive exercise
Premature Ovarian Insufficiency (POI): less common in this age group but possible
Asherman's syndrome: uterine synechiae (scarring) following uterine procedures, rare in this context
Anatomical abnormalities: mullerian agenesis, imperforate hymen.
Management
Initial Management:
Rule out pregnancy with a sensitive hCG test
If positive, refer for obstetric care and counseling
If negative, proceed with further investigations based on history and physical exam findings
Counsel the patient on the importance of adherence to OCPs if they wish to continue using them for contraception.
Medical Management:
Management of OCP-induced amenorrhea: If pregnancy is ruled out and no other endocrine disorder is found, continuation of OCPs or switching to a different formulation may resolve the issue
For diagnosed endocrine disorders: PCOS management may involve continuing OCPs (for ovulation suppression and cycle regularity), lifestyle modifications, and anti-androgens
Hyperprolactinemia is treated with dopamine agonists (e.g., bromocriptine, cabergoline)
Hypothyroidism is managed with levothyroxine
If the goal is future fertility, treatment strategies will be tailored to the specific endocrine cause.
Surgical Management:
Surgical intervention is generally not indicated for amenorrhea on OCPs unless there is a significant anatomical abnormality identified (e.g., septate uterus, cervical stenosis) or in cases of suspected ovarian pathology requiring biopsy or removal
Ovarian drilling may be considered in select PCOS patients resistant to medical management for fertility concerns.
Supportive Care:
Psychological support is important for adolescents experiencing menstrual irregularities or concerns about pregnancy
Education on reproductive health, contraception, and the implications of endocrine disorders is crucial
Regular follow-up appointments are necessary to monitor response to treatment and address any new concerns
Bone mineral density screening may be considered if amenorrhea is prolonged or associated with other risk factors for osteoporosis.
Complications
Early Complications:
Unintended pregnancy: Risk of continued use of OCPs during early pregnancy, potentially leading to teratogenic effects
Ectopic pregnancy: A life-threatening complication if pregnancy occurs
Emotional distress: Anxiety and fear related to amenorrhea and potential pregnancy
Missed diagnosis of serious endocrine disorders.
Late Complications:
Osteoporosis: due to prolonged hypoestrogenism if the amenorrhea is not due to pregnancy and represents an underlying endocrine issue with low estrogen levels
Infertility: if underlying endocrine disorders are not adequately managed
Cardiovascular risks: associated with certain endocrine disorders like PCOS and untreated hypothyroidism
Psychological sequelae: depression, anxiety related to chronic reproductive health issues.
Prevention Strategies:
Strict adherence to OCP regimen: emphasize consistent daily intake at the same time
Regular follow-up with healthcare providers to monitor OCP effectiveness and address any breakthrough bleeding or amenorrhea
Prompt pregnancy testing for sexually active individuals experiencing missed periods
Early and accurate diagnosis and management of underlying endocrine disorders
Patient education regarding contraceptive use and signs of pregnancy.
Key Points
Exam Focus:
Always rule out pregnancy first with an hCG test when a patient on OCPs presents with amenorrhea
Understand the different types of OCPs and how they affect bleeding patterns
Differentiate between OCP-induced amenorrhea, pregnancy, and other endocrine causes of amenorrhea (PCOS, hyperprolactinemia, thyroid dysfunction)
Know the key investigations for each differential diagnosis
Recognize the long-term implications of untreated endocrine disorders leading to amenorrhea.
Clinical Pearls:
For adolescents, a missed period on OCPs, even with perfect adherence, can cause significant anxiety
reassurance and prompt testing are key
Consider a progesterone withdrawal bleed test if pregnancy is ruled out and a diagnosis of ovulatory dysfunction is suspected, but OCPs are masking cycles
Always check TSH and Prolactin as part of the initial endocrine workup for menstrual irregularities
Be aware of the "silent" nature of some endocrine disorders
Continuous OCPs are designed to reduce or eliminate withdrawal bleeding, so amenorrhea in this context is expected, but pregnancy must still be ruled out.
Common Mistakes:
Failing to rule out pregnancy as the first step
Attributing amenorrhea solely to OCPs without a thorough endocrine workup
Inadequate history taking regarding sexual activity and OCP adherence
Misinterpreting bleeding patterns with continuous vs
cyclic OCPs
Delaying investigation of symptoms suggestive of underlying endocrine disorders
Not considering the impact of OCPs on pregnancy diagnosis (may interfere with hCG levels in very early stages, though generally not clinically significant for standard tests).