The absence of menstruation for three or more consecutive cycles in someone who previously had regular periods is medically termed secondary amenorrhea. Since pregnancy tests are negative, the physiological cause of pregnancy is ruled out, necessitating a deeper investigation into hormonal regulation. The menstrual cycle relies on precise communication between the brain’s hypothalamus, pituitary gland, and the ovaries, known as the hypothalamic-pituitary-ovarian (HPO) axis. When a signal along this axis is disrupted, menstruation ceases, and identifying the source of this disruption is the focus of a medical evaluation.
Common Lifestyle Triggers
A common, non-pathological reason for a missed period is functional hypothalamic amenorrhea (FHA), a disruption originating in the brain. This condition arises when lifestyle factors suppress the pulsatile release of Gonadotropin-Releasing Hormone (GnRH) from the hypothalamus. The brain perceives a state of stress or low energy and conserves resources by shutting down the reproductive system.
A frequent trigger is low energy availability, occurring when calorie intake does not sufficiently cover energy expended through exercise and daily metabolism. This imbalance, rather than low body weight alone, disrupts the hormonal signals that regulate the cycle. Hormones reflecting nutritional status, such as ghrelin and leptin, become altered, inhibiting the GnRH pulse generator. When GnRH release slows, the pituitary gland reduces its output of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), which are necessary to stimulate the ovaries.
Excessive physical training, particularly endurance sports, contributes to this low energy state. Chronic psychological or emotional stress, such as anxiety or major life changes, can also activate the body’s stress response system. This stress elevates cortisol, which inhibits GnRH secretion. The resultant low estrogen level (hypoestrogenism) prevents the uterine lining buildup and shedding that defines a period.
Endocrine Disorders and Hormonal Causes
Several systemic endocrine conditions can interrupt the HPO axis and cause secondary amenorrhea. Polycystic Ovary Syndrome (PCOS) is a frequently identified hormonal cause in reproductive-aged women, characterized by a complex imbalance of reproductive hormones. In PCOS, the ovaries often produce excess androgens, sometimes referred to as male hormones, which interfere with normal follicular development and ovulation.
This hormonal environment causes follicles to fail to mature and release an egg, leading to anovulation and the lack of a menstrual period. The sustained, non-fluctuating hormone levels in PCOS do not trigger the orderly phases of a normal cycle. Many individuals with PCOS also exhibit insulin resistance, where cells do not respond effectively to insulin, which can further stimulate the ovaries to produce androgens.
Dysfunction of the thyroid gland profoundly influences the menstrual cycle, as thyroid hormones regulate metabolism and interact with reproductive hormones. Hypothyroidism (an underactive thyroid) means the gland does not produce enough hormone, which can increase Thyroid-Releasing Hormone (TRH) from the hypothalamus. Elevated TRH can stimulate the pituitary gland to release prolactin, a hormone that suppresses ovulation.
Hyperprolactinemia, an abnormally high level of prolactin, independently causes amenorrhea by inhibiting the release of LH and FSH from the pituitary. While prolactin is associated with milk production, when elevated outside of pregnancy or breastfeeding, it strongly suppresses the reproductive axis. This elevation is often caused by a small, non-cancerous growth on the pituitary gland (a prolactinoma) or can be a side effect of certain medications.
Physical and Medication-Related Factors
In some cases, the problem is a physical barrier or an issue with the ovaries, rather than a hormonal signal disruption. Premature Ovarian Insufficiency (POI), sometimes called premature menopause, occurs when the ovaries stop functioning normally before age 40. POI is marked by the depletion or dysfunction of ovarian follicles, resulting in low estrogen and high Follicle-Stimulating Hormone (FSH) levels, as the pituitary attempts to stimulate the non-responsive ovaries.
Structural issues within the uterus can prevent menstrual flow even if the hormonal cycle is correct. Asherman’s Syndrome is a condition where scar tissue (intrauterine adhesions) builds up inside the uterine cavity. This often follows a Dilation and Curettage (D&C) procedure, C-section, or pelvic infection. This scarring prevents the normal buildup and shedding of the endometrium, meaning there is no tissue to generate a period.
Certain medications can interfere with the menstrual cycle and lead to secondary amenorrhea. Specific drugs, including some antipsychotics and antidepressants, can cause elevated prolactin levels, mimicking a prolactinoma. It is also common for the menstrual cycle to temporarily cease or become irregular after stopping certain forms of hormonal contraception, particularly long-acting progestin methods.
Diagnostic Steps and Medical Consultation
The next step in addressing secondary amenorrhea is a consultation with a healthcare provider to systematically identify the underlying cause. The initial workup involves a thorough medical history, including questions about recent lifestyle changes, medication use, and surgical procedures. This is followed by blood tests to assess the function of the hormonal control centers.
Standard initial laboratory tests include measuring serum levels of Thyroid-Stimulating Hormone (TSH) and Prolactin. The provider will also check gonadotropins (Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) and Estradiol to evaluate ovarian function and the HPO axis status. If symptoms suggest an excess of androgens (such as acne or excessive hair growth), levels of free testosterone may be checked to screen for conditions like PCOS.
Imaging is another important diagnostic tool, often involving a pelvic ultrasound to visualize the ovaries and uterus. This imaging can reveal polycystic ovaries or assess the thickness of the uterine lining, which may suggest conditions like Asherman’s syndrome. If blood tests show high prolactin or if there are symptoms like headaches or vision changes, a Magnetic Resonance Imaging (MRI) scan of the pituitary gland may be ordered to check for a tumor.
Identifying the cause is important for restoring fertility and for long-term health. If the cause involves chronically low estrogen levels (such as in FHA or POI), there is a risk of decreased bone mineral density and osteoporosis. Treatment focuses on correcting the underlying disorder through lifestyle modification, medication to regulate hormone levels, or addressing structural issues to ensure a return to a healthy cycle.