Amenorrhea - Types, Causes, Symptoms, Prevention and Treatment

Amenorrhea definition

Amenorrhea is characterised by the absence or the abnormal stoppage of menstrual cycles in a woman of reproductive age. Menstruation is an essential natural phenomenon for every female and occurs throughout the reproductive years, starting from adolescence to menopausal age. 

The menstrual cycle typically has four main stages, during these stages, the uterine lining (endometrium) thickens in preparation for pregnancy. If there is no pregnancy, the uterus starts to shed this lining accompanied by bleeding, resulting in monthly menstruation throughout a woman's reproductive years. A regular menstrual cycle repeats once in every 21-35 days with duration of 2-8 days.

Prolonged stoppage of the menstrual cycle in women may lead to specific problems such as osteoporosis, fractures, infertility, and psychosocial developmental delays, among other things. Therefore, it is essential to detect this menstrual distress in women at an early age to reduce the risks of experiencing reproductive issues during premenstrual and postmenstrual conditions.

Amenorrhea meaning

The term "amenorrhea" was coined in 1804. It originates from Modern Latin, a combination of the Greek privative prefix a- meaning "not," the word "men," which means "month," and rhein, which means "to flow." This term specifically refers to the absence of menstruation.

Types of amenorrhea

Amenorrhea is categorized into two types based on the onset, which include: 

• Primary amenorrhoea
• Secondary amenorrhoea

Primary amenorrhoea: This condition refers to the absence of the first menstrual cycle during normal development.



Secondary amenorrhoea: The condition of secondary amenorrhea is defined as the lack of menstruation for a minimum of 3 consecutive months in women with previously regular menstrual cycles or for a minimum of 6 months in any woman who has experienced at least one previous spontaneous menstruation.

Prevalence of amenorrhea

Amenorrhea affects 1.5–3% of women in their reproductive years. While primary amenorrhea is uncommon, secondary amenorrhea is relatively common among women of reproductive age, compared to the 2-5% prevalence of secondary amenorrhea in the general population, up to 44% of women who engage in intense exercise would experience this condition. This substantial difference underscores the potential consequences of vigorous physical activity on women's reproductive health.

The incidence of primary amenorrhea is extremely rare, affecting less than 0.1% of the general population, whereas secondary amenorrhea is more common, with an incidence ranging from 0.7% to 4% in the general population. This condition is prevalent among women under 25 years old with a history of menstrual irregularities.

Amenorrhea symptoms

Amenorrhea symptoms, such as missed periods, are the primary indicators of amenorrhea. Depending on the underlying causes, a woman may also experience additional amenorrhoea signs and symptoms, including: 

• Excessive facial hair: There is a connection between hirsutism (growth of excessive male-pattern hair in women on certain parts of body) and the androgen hormone class. An increase in these hormones can lead to this condition, which is noticeable in cases of amenorrhea .
• Hair loss: The signs of female pattern hair loss (FPHL), including changes in hair growth, sudden hair loss, and thinning of scalp hair, are closely related to amenorrhea caused by hormonal imbalances. 
• Underdeveloped breasts: It is crucial to determine the stage of breast development. Generally, because of the absence of hormonal activity in the ovaries, there is no appearance of breast development and menarche. This disorder is usually identified in adolescence, during the diagnosis of primary amenorrhoea and delay in pubertal signs. No breast growth (such as Tanner stage 1) suggests no oestrogen exposure, while normal maturation indicates oestrogen exposure, likely from functional ovaries. 
• Milky discharge from the breasts: When menstrual periods become irregular or stop, milky discharge from the breast may be seen in some patients. Milk production can be influenced by several hormones, such as thyrotropin-releasing hormone (TRH), prolactin, and oestrogens. 
• Changes in vision: Pituitary tumours, such as prolactinomas, which emit hormones that directly alter the menstrual cycle, tiny pituitary tumours often don't affect vision, but larger tumours (typically more than 1 cm) might impair one or both eyes' ability to see.
  

Risk factors of amenorrhea

The following are some of the common risk factors that may increase the risk of amenorrhoea:

• Vigorous exercise: The impact of vigorous exercise on the menstrual cycle can be diverse. It can lead to subtle changes such as delayed spontaneous menses or anovulatory (no ovulation) cycles or even result in the loss of spontaneous menses altogether, increasing the risk of amenorrhoea. 
• Obesity: Obesity has a significant impact on reproductive function, particularly ovulatory disorders, due to intricate endocrine mechanisms that disrupt the delicate balance of neuroendocrine and ovarian functions, leading to reduced ovulation rates and resulting in difficulty for individuals with obesity in maintaining optimal reproductive health. 
• Anorexia nervosa: Adolescents with eating disorders, such as anorexia (a loss of interest in food or general loss of appetite) or bulimia (eating large amounts of food in a short period), have a risk of developing amenorrhoea due to severe malnourishment. .
• Genetics: Mutations in the FMR1 gene, associated with fragile X syndrome, can lead to an increased risk of amenorrhea due to their impact on ovarian function. FXPOI (Fragile X-associated Primary Ovarian Insufficiency) can cause reduced fertility and symptoms like vaginal dryness, mood swings, and hot flashes. This condition can start as early as 11 years of age, leading to irregular or absent menstrual cycles and delayed development of secondary sexual characteristics. 
  

Amenorrhea causes concern as it may signal an underlying health issue rather than being a disease itself. It may be a natural part of life, such as during pregnancy or breastfeeding, or it could signal a health problem like polycystic ovary syndrome (PCOS). Given its association with health conditions linked to infertility, addressing the underlying causes of amenorrhea is crucial. The following are the causes of amenorrhea:

Primary amenorrhea causes

Primary amenorrhea may occur due to two leading causes, which includes:

• Genetic or chromosomal irregularities: These disrupt the normal functioning of the ovaries. Turner syndrome, a condition resulting from the partial or complete absence of an X chromosome, and androgen insensitivity syndrome, often characterized by elevated testosterone levels, are two examples of genetic abnormalities that can cause delays or disturbances in the menstrual cycle. 
• Hypothalamus and Pituitary Gland-Related Issues: These issues may cause hormonal imbalances that can result in the absence of menstruation. Factors like eating disorders, rigorous physical activity, severe physical or mental strain, or a blend of these elements can also interfere with the regular operation of the hypothalamus or pituitary gland, causing a delay in the start of menstruation. 

In some instances, medical issues such as the absence of reproductive organs or blockage of reproductive pathways can result in primary amenorrhea. When parts of the reproductive system are missing, it can lead to hormonal imbalances, and when combined with hypothalamic or pituitary issues, it can hinder menstruation. Blockages can also obstruct menstrual flow, causing primary amenorrhea even if a girl's menstrual cycles are normal.

Secondary amenorrhea causes

Secondary amenorrhea may result from different causes, such as:

• Natural causes: Pregnancy serves as the most frequent natural cause of secondary amenorrhea. Additional physiological causes include breastfeeding and menopause.
• Medications and therapies: Using contraceptives can lead to the absence of menstruation. After stopping these contraceptives, it may take a few months for the menstrual cycle to return to normal. Additionally, certain medications, such as specific antidepressants and blood pressure medications, can raise hormone levels, which may inhibit ovulation and the menstrual cycle. 
• Certain treatments: Chemotherapy and radiation treatments can significantly impact the ovaries, leading to a cessation of menstruation in women with hematologic breast cancer. Effect on fertility may be temporary, particularly in younger women. After the procedure, dilation and curettage (D&C), which can be performed for heavy bleeding, miscarriage, caesarean section, or uterine fibroid treatment, may lead to the development of scar tissue in the uterus lining, blocking normal shedding in the menstrual cycle . 
• Hypothalamic amenorrhea: Hypothalamic amenorrhea is a condition that arises when the hypothalamus, a gland in the brain responsible for regulating body processes, slows the release of gonadotropin-releasing hormone (GnRH), the hormone that initiates the menstrual cycle. 
• Gynaecological conditions: Especially those that lead to or result from a hormonal imbalance may also cause secondary amenorrhea, including:
• Polycystic ovary syndrome: PCOS is a condition that arises when a woman's body produces an excessive amount of androgens, a type of hormone. Higher levels of androgens can lead to fluid-filled sacs or cysts forming in the ovaries, which can disrupt the ovulation process. Women with PCOS typically experience either amenorrhea or irregular periods, also known as oligomenorrhea.
• FXPOI: FXPOI, also known as Fragile X-Associated Primary Ovarian Insufficiency, occurs when a woman's ovaries cease to function before the usual age of menopause, typically around 40 years old. This particular condition is the result of specific genetic changes on the X chromosome and is frequently observed in women seeking treatment for amenorrhea .
• Thyroid problems: The thyroid is a gland resembling a butterfly situated at the lower part of the neck, beneath the Adam's apple. It generates hormones that regulate metabolism and impact puberty and the menstrual cycle. When the thyroid functions too much (hyperthyroidism) or too little (hypothyroidism), it can cause irregularities in the menstrual cycle, including amenorrhea.
• Pituitary tumours: The pituitary gland, nestled at the base of the brain, is a key player in regulating the production of hormones that influence metabolism and the reproductive cycle. However, the presence of tumours on the pituitary gland, typically noncancerous, can disrupt this delicate hormonal balance, potentially leading to irregularities in the menstrual cycle.
  

Complications of amenorrhea

Amenorrhea is not typically life-threatening, but the absence of menstrual periods may signal underlying severe health issues, such as: 

• Osteoporosis: The ovaries produce oestrogen, an essential hormone for preserving bone density and strength. A decrease in levels of oestrogen leads to a loss of the menstrual cycle. Such individuals could be at higher risk of developing osteoporosis and experiencing fractures.   
• Infertility: Low levels of luteinizing hormone (LH), resulting from prolactin-induced suppression of hypothalamic, gonadotropin-releasing hormone (GnRH) secretion, can lead to anovulation, in this condition the ovaries do not release eggs, and there is oligomenorrhea (infrequent menstrual periods) or amenorrhea (absence of menstrual periods). 
• Cardiovascular diseases: It is widely recognized that women experience a significant increase in the risk of cardiovascular disease and one potential reason for this is the substantial decrease in oestrogen levels. 
• Exercise-induced secondary amenorrhea, which leads to a deficiency in oestrogen, may disrupt the cardioprotective mechanisms associated with oestrogen .
• Lipoprotein profiles are also negatively impacted, which is linked to a higher chance of experiencing cardiovascular issues. 
• Endometrial hyperplasia: Anovulatory amenorrhea, a condition marked by the absence of ovulation and menstrual periods, is often caused by "unopposed" oestrogen, where the levels of oestrogen outweigh those of progesterone. The imbalance of hormones in the body can result in a higher chance of developing endometrial hyperplasia, a condition that involves the abnormal thickening of the lining of the uterus.
  

Amenorrhea diagnosis

The diagnosis of amenorrhea may vary according to underlying conditions. A gynaecologist asks questions about the history of the present illness and menstrual function. Based on that information, a gynaecologist chooses the diagnostic tests and performs a single or a combination of the following tests: 

• Medical history: A gynaecologist asks questions about past medical history, medication history, family history and menstrual function such as menstrual cycle frequency, date of first day of last menstrual period, cycle regularity, duration of bleeding, volume of bleeding and other symptoms. 
• Physical examination: It is one of the significant initial tests to perform in individuals with no menstruation observed even at the age of puberty (16 years or above) 
• Thyroid function test: Monitoring TSH levels in the blood offers valuable insights into thyroid health. Irregular menstrual patterns like amenorrhea can be linked to thyroid gland overactivity (hyperthyroidism) or underactive (hypothyroidism). 
• Ovary function test: This test definitively measures the levels of key hormones like follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH) in the blood to accurately assess ovarian function. Elevated AMH levels are strong indicators of polycystic ovary syndrome, while low or undetectable AMH levels are clear indicators of menopause or primary ovarian insufficiency .
• Androgen test: It is crucial for assessing the levels of male hormones in the body. It is essential for both men and women to maintain appropriate levels of androgens for overall health. Elevated androgen levels in women can serve as an important indicator of polycystic ovary syndrome (PCOS). 
• Hormone challenge test: This test involves taking hormonal medication for seven to ten days to stimulate a menstrual cycle. Through this test, healthcare professionals can gain valuable insight whether periods have ceased due to a lack of oestrogen. 
• Premutation of the FMR1 gene through screening: Variations in this gene can lead to irregular ovarian function, potentially causing amenorrhea. 
• Ultrasound: Ultrasonography of the pelvis and reproductive organs is a painless and non-invasive imaging test, an important diagnostic imaging technique for an amenorrhea patient to observe the development of the endometrium as it develops during the menstrual cycle. It is also crucial for assessing the regular presence and shape of reproductive organs. 
• Chromosome evaluation: This test is also known as a karyotype, counts and evaluates body cell chromosomes to identify abnormalities causing amenorrhea. 
• Computed tomography: CT scans can assess the regular appearance of the uterus, ovaries, and kidneys, which is helpful in detecting abnormalities. 
• Magnetic resonance imaging (MRI): It utilizes radio waves and a strong magnetic field to generate high-resolution images of soft tissues in the body. It can be used to check for a pituitary tumour or to examine reproductive organs.
• Hysteroscopy: It involves the insertion of a thin, illuminated camera through the vagina and cervix to enable a healthcare professional to observe the interior of the uterus.
  

Amenorrhea treatment

Management of amenorrhea treatment varies depending on the underlying causes; a gynaecologist chooses the therapy based on the underlying cause, patient's overall health and the desires of the patient. The following are the treatment approaches that can be used in treating amenorrhea:

Primary amenorrhea treatment

Treatment for primary amenorrhea generally focuses on addressing the underlying disorder that is causing it through lifestyle modification, medications, surgeries, or a combination of both, including: 

• Lifestyle changes: If lifestyle factors contribute to primary amenorrhea, a gynaecologist may recommend changes in the patient's weight, stress levels, and physical activity. 
• Watchful waiting(observation): Primary amenorrhea treatment may begin with watchful waiting, depending on the person’s age and the result of the ovary function test. 
• Medications: The treatment options for menstrual cycle disturbances in cases of high prolactin levels include medications that lower prolactin, cyclical progestogen, and hormone replacement therapy (HRT). 
• Patients seeking pregnancy can use prolactin-lowering drugs to improve fertility while also using a contraceptive pill for controlling birth. 
• Hypogonadotropic amenorrhea, a combination of oestrogen and progestogen, may be recommended to prevent oestrogen deficiency or for psychological benefits. If contraception is required, oral contraception may be suggested for both cycle regulation and fertility control. 
• Surgery: Primary amenorrhoea caused by genetic or chromosomal problems can be treated by surgical intervention.
• For example, women with a genetic condition known as 46, XY gonadal dysgenesis, may have an increased risk of ovarian cancer due to abnormal ovarian development. Laparoscopic surgery is recommended to remove the ovaries.

Secondary amenorrhea treatment

Treatment for secondary amenorrhea depends on the underlying cause, which includes medical and surgical treatments, such as: 

• Medications: The following are the common medical treatments that can be used to treat secondary amenorrhea: 
• Oral contraceptives or other hormonal medications: Certain medications can be used to trigger ovulation and restart the menstrual cycle 
• Estrogen replacement therapy (ERT): This therapy can be used to balance the levels of hormones and restart menstruation in women with Fragile X- associated primary ovarian insufficiency (FXPOI) or primary ovarian insufficiency.
• Additionally, ERT may aid in reducing the risk of osteoporosis in women with FXPOI. However, it's important to note that ERT may increase the risk of uterine cancer. To mitigate this risk healthcare professionals may prescribe progestin or progesterone alongside ERT   
• Surgery: Surgical intervention for amenorrhea is not usual but might be suggested in specific cases, includes :
• Hysteroscopic resection for uterine scarring: This can occur after the removal of uterine fibroids, a caesarean section, or a dilation and curettage (D&C) procedure. The removal of scar tissue through a hysteroscopic resection can aid in reestablishing the menstrual cycle. 
• Pituitary tumour: It may be treated with medications to reduce its size. If this is ineffective, surgery may be necessary to remove the tumour. Although pituitary tumours are not cancerous, they can cause complications as they grow. These tumours can pressure surrounding blood vessels and nerves, such as the optic nerve, leading to vision loss. In some cases, radiation therapy may be used either in combination with surgery or as the sole treatment for those who are not suitable candidates for surgery.
  

Prevention of amenorrhea

Prevention of amenorrhea is not possible as it can be caused by different factors such as genetics, certain medical conditions, hormonal imbalances or anatomical issues. However, adopting the healthy lifestyle by following the below mentioned can help to reduce the risk of certain types of amenorrhea:

• Weight: Body weight significantly affects the menstrual cycle. Being overweight or underweight can disrupt its regularity. Maintaining a healthy weight is essential to balance hormone levels and reestablish a normal cycle. Body weight plays a crucial role in regulating menstrual cycle
• Stress: Identify the different aspects of life that are causing stress and take steps to reduce their impact. If you find it challenging to manage stress alone, consider seeking help from family, friends, healthcare provider, or a skilled listener such as a counsellor.
• Physical activity: Adjusting the physical activity level can play a crucial role in restoring the menstrual cycle.

It is essential to keep a detailed record of period dates, duration, and any issues encountered. Remember, the first day of bleeding signifies the start of the menstrual cycle.

Difference between amenorrhea and dysmenorrhea

Amenorrhea vs dysmenorrhea

Amenorrhea and dysmenorrhea are the common gynaecological conditions that affect the female reproductive health. The following are the differences between amenorrhea and dysmenorrhea:

Frequently Asked Questions (FAQs) on Amenorrhea

How does amenorrhea trigger?

Specific contraceptive methods, antidepressants, and blood pressure medications function by increasing hormone levels, effectively preventing ovulation and menstruation. Some chemotherapy and radiation treatments may also result in amenorrhea.

Is having no period harmful to the body?

Continuous absence of a menstrual cycle in a woman may cause problems such as osteoporosis, fractures, and psychosocial developmental delays, among other things. Low levels of oestrogen in the body may decrease fertility and increase the risk of not being able to conceive.

What is the average age for amenorrhea?

The average age for amenorrhea is 15 years old in the presence of normal growth and secondary sexual development or 13 years old in the absence of normal growth or and secondary sexual development.

What is a differential diagnosis of amenorrhea?

Differential diagnosis of amenorrhea includes vaginal agenesis (absence of a vagina), androgen insensitivity syndrome, Turner syndrome (45, X), and mosaicism (presence of two or more genetically different cell lines in an individual). Additional diagnoses should be considered for patients exhibiting both primary and secondary amenorrhea. 

Does amenorrhea need surgery?

Usually, surgical treatment for amenorrhea is not required. Most of the cases can be managed by lifestyle changes and medications. However, it may be recommended in certain situations, such as anatomical abnormalities, uterine scarring, and tumours.

What is the rare cause of amenorrhea?

In rare cases, the presence of physical issues, such as missing reproductive organs or blockage of reproductive passageways, can result in primary amenorrhea.

What is the examination for primary amenorrhoea?

In cases of primary amenorrhea with normal pubertal development, a pelvic examination can be crucial in identifying conditions such as imperforate hymen, transverse vaginal septum, or the absence of cervical or uterus.

What blood tests are done to investigate amenorrhea?

A complete blood cell count, urinalysis, and serum chemistries are essential. After ruling out pregnancy, it's also recommended to regularly measure serum prolactin, FSH, and thyrotropin levels during the initial assessment of amenorrhea.

Department of Gynecology