Causes of Intermenstrual Bleeding

Structural Causes

The American College of Obstetricians and Gynecologists notes that uterine fibroids (leiomyomas) are among the three most common structural causes in premenopausal women, typically presenting with heavy or prolonged menstrual bleeding and an enlarged, irregular uterus on palpation 1, 3
Adenomyosis frequently coexists with fibroids, presenting with heavy menstrual bleeding, dysmenorrhea, and dyspareunia, most commonly affecting women in their 40s 1, 2
Endometrial hyperplasia and malignancy must be excluded, particularly in postmenopausal women where endometrial cancer is the most serious etiology 1

Women on anticoagulation, particularly NOACs like rivaroxaban, have significantly increased risk of abnormal uterine bleeding (27% vs 8.3% with warfarin) 1
The Endocrine Society recommends that polycystic ovary syndrome (PCOS) is a common cause of irregular periods, affecting 4-6% of women in the general population, characterized by hyperandrogenic chronic anovulation with low mid-luteal phase progesterone levels 4, 5
Hypothalamic amenorrhea (hypogonadotropic hypogonadism) causes oligomenorrhea and infertility without signs of hyperandrogenemia, associated with disturbed pituitary gonadotropin secretion 4, 5
Thyroid dysfunction can cause menstrual irregularities and should be evaluated with TSH levels 4, 2
Hyperprolactinemia may result from pituitary adenomas, hypothyroidism, or medications (antipsychotics, antiepileptics), requiring prolactin level measurement 4, 5

The Centers for Disease Control and Prevention recommends that progestin-only contraceptives (pills, DMPA, implants) frequently induce irregular bleeding patterns, especially during the first 3-6 months, though this may persist longer with implants 6
Antiepileptic drugs (carbamazepine, phenobarbital, phenytoin) induce hepatic cytochrome P450-dependent steroid hormone breakdown, reducing biologically active sex hormone concentrations and potentially causing menstrual disturbances 4, 5

Women with PCOS have elevated prevalence of menstrual irregularities due to hyperandrogenism, insulin resistance, and anovulation, manifested as hypersecretion of luteinising hormone and ovarian dysfunction 4, 5
Thyroid disorders require evaluation with TSH measurement, as both hypothyroidism and hyperthyroidism can cause abnormal bleeding patterns 4, 2

Unexplained vaginal bleeding suspicious for serious conditions requires evaluation before initiating treatment, as progestin-only contraceptives might mask symptoms of underlying pathology including pelvic malignancy 6
Pregnancy must be ruled out in all reproductive-age women before proceeding with evaluation 2