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Secondary Amenorrhea

What Is It, Causes, Treatment, and More

Author: Nikol Natalia Armata

Editors: Ahaana Singh, Lisa Miklush, PhD, RN, CNS

Illustrator: Jillian Dunbar


What is secondary amenorrhea?

Secondary amenorrhea is the absence of regular menstrual periods for at least 3 months or the absence of irregular menstrual periods for 6 months or more.

What is the difference between primary and secondary amenorrhea?

The main difference between primary and secondary amenorrhea is that with primary amenorrhea, the individual has not yet had their first menstrual period and is older than the typical age at which menstruation begins. Primary amenorrhea is typically defined as the complete absence of menstruation by the age of 15. In contrast, with secondary amenorrhea, the individual has menstruated in the past, but their menstrual periods have stopped occurring.

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What causes secondary amenorrhea?

Secondary amenorrhea can be caused by various conditions that affect the menstrual cycle, including pregnancy, anovulation, estrogen deficiencies, and reproductive tract obstructions. In addition, certain lifestyles may increase the risk of secondary amenorrhea.  

Pregnancy

Pregnancy is the most common cause of secondary amenorrhea because pregnant individuals do not experience menses. The possibility of pregnancy should be routinely investigated in every individual of childbearing age that presents with secondary amenorrhea. 

Anovulation

Anovulation refers to the lack of ovulation, or the inability to release an egg during the menstrual cycle. This results in a hormonal imbalance of estrogens and progesterones, preventing the inner layer of the uterus (i.e., endometrium) from thickening and shedding as it otherwise would during menstruation. There are various causes of anovulation, including polycystic ovary syndrome (PCOS), in which the ovaries are enlarged and have small cysts; hypothyroidism, characterized by low levels of thyroid hormones; and hyperprolactinemia, characterized by high levels of prolactin that can be caused by a pituitary tumor. In addition, certain medications, such as antidepressants, may lead to anovulation. Notably, hormonal birth control pills prevent ovulation by decreasing the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH). These hormonal changes suppress the thickening of the endometrium and can lead to secondary amenorrhea. 

Estrogen Deficiency

Deficiencies in estrogen, a sex hormone released by the ovaries, can also lead to secondary amenorrhea. Without adequate estrogen levels, the endometrium will be atrophic -- very thin -- and may not be able to shed. Estrogen deficiency can result from perimenopause, the lifestage prior to menopause, during which levels of sex hormones are lower than usual. An individual may also experience estrogen deficiency due to premature ovarian failure, which is when the ovaries stop functioning before the age of 40. Hypothalamic-pituitary insufficiency, presenting as low levels of LH and FSH, also decreases estrogen production.
 

Reproductive Tract Obstruction

Menses generally cannot occur if there is any type of obstruction in the reproductive tract. Stenosis, or narrowing of the lower reproductive system, is one of the main causes of flow obstruction. Similarly, the presence of fibrous tissue in the uterus or cervix, also known as adhesions, can cause Asherman syndrome and block the menstrual flow. This syndrome usually presents after surgical procedures, such as dilation and curettage, during which the cervix is dilated and the endometrium is scraped by a spoon-shaped tool to remove any excess tissue remaining inside the uterus. 

Lifestyle

Any dramatic lifestyle changes can affect hormone levels and may subsequently cause secondary amenorrhea. Too much stress or extreme athletic training, as well as severe eating disorders, may lead to delayed menstruations. 


How common is secondary amenorrhea?

Secondary amenorrhea occurs in approximately 2% to 5% of women.

What are the signs and symptoms of secondary amenorrhea?

Signs and symptoms of secondary amenorrhea usually depend on the underlying cause of the condition. If pregnancy is causing secondary amenorrhea, early symptoms typically include nausea, tiredness, and breast tenderness. Common signs of PCOS include excessive hair growth (i.e., hirsutism), acne, weight gain, and difficulty getting pregnant. In cases of hypothyroidism, individuals may present with fatigue, dry and flaky skin, hair loss, and changes in nail color, shape and growth. Palpitations, or heartbeats that suddenly become more noticable, can also be a symptom of hypothyroidism. With hyperprolactinemia, individuals may experience headaches, vision changes, and milky nipple discharge (i.e., galactorrhea). Usually, estrogen deficiency presents with hot flashes, mood changes, and bone weakness. Finally, reproductive tract obstruction often involves abdominal pain. 

Can secondary amenorrhea cause infertility?

Secondary amenorrhea itself cannot cause infertility; however, some of its underlying causes are frequently associated with infertility. All causes of anovulation affect the individual's ability to conceive. If the ovaries do not release eggs or release them infrequently, fertilization will likely not occur naturally. In addition, adhesions between the uterine walls could also complicate pregnancies since the remaining scar tissue may not allow the fetus to implant into the uterus. If the primary causes cannot be treated, assisted reproductive therapy may be suggested. 

How is secondary amenorrhea diagnosed?

Diagnosis begins with an assessment of the individual’s medical history and a physical examination. History should cover a full menstrual history, including the date of the individual’s most recent menstrual period and their overall pattern of menstruation. Additionally, methods of contraception, if used, should be noted. During physical examination, the provider will assess any related signs and symptoms. 

Further diagnostic testing, such as blood and urine tests, are usually initiated to assess the potential cause. To rule out pregnancy, a β-hCG test is always performed. If the β-hCG test is negative, hypothyroidism should be excluded by measuring the levels of thyroid stimulating hormones. Next, the levels of sex hormones, specifically FSH, LH, estrogen, and progesterone, are also often evaluated. 

If hyperprolactinemia is suspected, prolactin levels may also be measured. Further diagnostic testing, such as a computed tomography (CT) scan or magnetic resonance imaging (MRI), may be performed to determine the presence of a pituitary tumor.

How is secondary amenorrhea treated?

To treat secondary amenorrhea, it is important to diagnose and treat its underlying cause. Most cases of PCOS are treated with progesterone-containing or combined (estrogen and progesterone) oral contraceptive pills to regulate the menstrual cycle. With hypothyroidism, thyroid hormones are usually prescribed, causing a rapid restoration of menstruation. Meanwhile, hyperprolactinemia is treated with dopamine agonists or removal of the pituitary tumor. Ovarian failure could be treated with hormone replacement therapy, depending on the patient’s age, symptoms, and other risk factors. Lastly, cervical stenosis and Asherman syndrome can be treated hysteroscopically, which involves passing a thin, flexible tube into the uterus.

What are the most important facts to know about secondary amenorrhea?

Secondary amenorrhea refers to the absence of regular menstrual periods for 3 months or more or irregular periods for 6 months or more. Secondary amenorrhea can be caused by various conditions, including pregnancy, anovulation, estrogen deficiencies, reproductive tract obstructions, as well as dramatic lifestyle changes. Symptoms of individuals with secondary amenorrhea vary depending on the underlying cause of the condition. Some of those underlying causes are frequently associated with infertility, and if not resolved, assisted reproductive therapy may be suggested. Diagnosis of secondary amenorrhea involves a thorough medical history review, physical examination, blood tests, and, occasionally, imaging. Treatment largely depends on the underlying cause. 

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Related links

Amenorrhea
Estrogen and progesterone
Hyperprolactinemia
Hypothyroidism

Resources for research and reference

Cooper D., & Mahdy, H. (2020). Oral contraceptive pills. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK430882/ 

Fauci, A., & Harrison, T. (2009). Harrison's manual of medicine (17th ed.). New York: McGraw-Hill Medical.

Heiman, D. (2009). Amenorrhea. Primary Care: Clinics in Office Practice, 36(1): 1-17. DOI: 10.1016/j.pop.2008.10.005

Lord, M., & Sahni, M. (2020). Secondary amenorrhea. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK431055/

Sakala, E. (2017). USMLE step 2 CK lecture notes 2018: Obstetrics and gynecology. New York: Kaplan Publishing.