Primary Amenorrhea

What is Primary Amenorrhea?

Amenorrhea refers to the unusual condition where a woman of childbearing age doesn’t get her period. It can be split into two types: primary and secondary amenorrhea. Primary amenorrhea occurs if a girl hasn’t started her period by the age of 15 or within three years of when her breasts start to grow, known as thelarche. Secondary amenorrhea describes when a woman, who usually has regular periods, doesn’t have one for three months or more, or when any woman doesn’t have a period for six months after having at least one spontaneous period.

The average age for a girl to start her period, also known as menarche, is about 12.4 years. However, this can change based on factors specific to the individual like ethnicity, weight, and nutritional health. The onset of breast development or thelarche usually happens between the ages of 8 and 10, with periods starting within the next 2 to 3 years. Girls who fit the criteria for either primary or secondary amenorrhea should have an evaluation. Moreover, girls who are aged 13 with primary amenorrhea and no signs of puberty – like breast development or the growth of pubic and underarm hair – must also be evaluated for delayed puberty.

The main causes of primary amenorrhea can be grouped into categories like abnormalities in sexual development and anatomy, ovarian insufficiency, disorders of the hypothalamus or pituitary glands or other endocrine glands. Sometimes, certain bodily processes or medications can cause primary amenorrhea, although these are more often linked with secondary amenorrhea. Testing for amenorrhea usually involves a detailed personal history check and physical examination, a urine pregnancy test, blood tests to check hormone levels and pelvic imaging. More tests may be required based on the patient’s specific symptoms.

Treatment depends on what’s causing the amenorrhea. This might involve changes in lifestyle, hormone or other medication therapies, surgery or mental health support. So, every healthcare professional should aim to improve their expertise in managing primary amenorrhea. They should keep updating their knowledge, skills, and strategies to promptly diagnose and effectively treat the condition. This will help in coordinating the care better and improve the patient outcomes.

What Causes Primary Amenorrhea?

There are four key parts in your body that need to function properly to have a normal menstrual cycle: the hypothalamus, anterior pituitary gland, ovary, and the outflow genital tract, which includes the uterus, cervix, and vagina. If any of these parts aren’t working properly, menstrual bleeding can’t happen.

Primary amenorrhea, which is when a girl doesn’t start her periods by the age of 16, can happen for many reasons. But most of the time, it’s because of problems with the ovaries (43% of cases), lack of normal reproductive organs (10%-15% of cases), and delay in growth and puberty (14% of cases). Other common causes, which only account for 2% to 7% of cases, include issues with the hypothalamus, obstructions in the vagina, and conditions like polycystic ovary syndrome and hypopituitarism, which affects the production of hormones. There can be other rare causes too, and also remember that a pregnancy can also cause menstruation to stop. Certain factors that cause secondary amenorrhea, which is when periods that were regular become irregular, can present as primary amenorrhea.

Disorders of sexual development (DSD) refer to conditions that you’re born with that cause abnormal development of your reproductive system and genitals. These conditions can be due to problems with your anatomy, gonads, and chromosomes.

One such condition is Müllerian Agenesis, where the body doesn’t properly form certain parts of the female reproductive system like the fallopian tubes, uterus, and upper part of the vagina during development in the womb. This condition accounts for about 10% to 15% of primary amenorrhea cases. Those affected usually have normal ovarian function, external female genitalia, and the development of female secondary sex characteristics, but might also have other abnormalities in the urinary system and skeletal system, such as only one kidney or scoliosis.

Some types of primary amenorrhea are caused by the body not producing certain enzymes or receptors properly. For example, aromatase deficiency leads to overproduction of testosterone because the ovary fails to convert testosterone to estrogen, which can result in ambiguous genitalia.

Issues with the hypothalamus or the pituitary gland can also cause primary amenorrhea. Problems with these areas lead to low levels of certain hormones necessary for menstruation and reproduction.

Ovarian dysfunction, or problems with the ovaries operating as they should, is another common cause of primary amenorrhea. In these cases, the ovaries do not respond in the necessary ways for menstruation and reproduction, resulting in low estrogen production.

Other hormonal abnormalities can affect the hypothalamus, pituitary, and ovaries (HPO) axis, which is the interaction between these parts that is necessary for the menstrual cycle and reproduction.

Conditions such as pregnancy and lactation as well as certain medications can also cause primary amenorrhea. During pregnancy and lactation, certain hormones are increased, which suppresses the normal menstrual cycle. Some medications can also affect the menstrual cycle, leading to amenorrhea.

Risk Factors and Frequency for Primary Amenorrhea

In the United States, it’s quite rare for girls not to start their periods by age 15, with only about 2% falling in this category. Müllerian agenesis, a condition in which a woman is born without certain reproductive organs, affects 1 in 4,500 to 5,000 females. Complete Androgen Insensitivity Syndrome (CAIS), a condition where a person is genetically male but has the physical traits of a female, affects 1 in 20,000 to 99,000 genetic males. Lastly, it is reported that up to 7% of females have unusual structures in their womb or vagina.

Signs and Symptoms of Primary Amenorrhea

Primary amenorrhea is a condition where a woman of reproductive age has never menstruated. Doctors need to investigate when:

• A 15 year old girl has secondary sexual features, like breast development and bodily hair, but has never had a period.
• There is an absence of menstruation and secondary sexual characteristics in a girl who is 13 years old.

To diagnose the cause of primary amenorrhea, doctors will ask about the patient’s menstrual history, the timing of body changes like breast development, hair growth, and growth patterns. They will also ask about any cyclic abdominal pain as this could suggest a blockage in the reproductive tract, like an imperforate hymen or cervical atresia.

It’s also crucial to ask about the patient’s medical history, lifestyle, and medication use, as things like chronic illnesses, chemotherapy or radiation exposure, eating disorders, or heavy athletic training could affect menstruation. Extreme weight loss, symptoms like inability to smell (anosmia), milk secretion from the breasts (galactorrhea), headaches, or vision changes could also hint at central nervous system or pituitary disorders. A detailed family history is also important as some causes of primary amenorrhea can be inherited.

A physical exam is also part of the diagnosis process. The doctor will check height, weight, and body mass index (BMI). Short height and the absence of secondary sexual characteristics could be a sign of gonadal dysgenesis. Low body weight could be a sign of functional hypothalamic amenorrhea (FHA) due to malnutrition or physical, psychological, or emotional stress.

The doctor will also check for physical signs like vision changes, thyroid enlargement, hair growth, and presence of acne to give clues about the underlying cause. They will assess the patient’s breasts for signs of estrogen exposure, check for signs of heart or lung disease, for changes in the abdomen, including palpable masses, and will perform a pelvic exam looking at the external genitalia maturity, length of the vagina, the prescence or absence of the cervix and other abnormalities.

Lastly, although not always necessary, a doctor might perform a rectal examination to check for hematocolpos (accumulation of menstrual blood in the vagina) in patients with an obstructive anomaly, and check for any abnormalities in the extremities, such as joint pain or shortening of the fourth metacarpal, and small metatarsal bones, commonly seen in Turner syndrome.

Testing for Primary Amenorrhea

If a patient has not yet started menstruating, a condition referred to as primary amenorrhea, doctors perform various diagnostic studies to identify the cause. The kind of tests run can depend on the patient’s age and what the doctor finds during the examination. However, all patients are generally required to undergo several initial tests:

• A pregnancy test
• A pelvic ultrasound which is usually done via the abdomen
• Blood tests to check levels of various hormones: FSH, LH, estradiol, prolactin, and thyroid-stimulating hormone (TSH)

Depending on the results of these initial tests, additional tests may be required. Such tests can help identify conditions such as hyperandrogenism, delayed puberty, and chronic diseases like liver disease or inflammatory bowel disease. The tests can include detailed hormone tests, bone age radiography, complete blood count (CBC), liver function tests and others. If certain conditions are suspected (like Turner syndrome), a karyotype test can be performed, and MRI might be considered. If there are grounds to believe there might be a genetic defect (like Kallman syndrome), a visit to a genetic counselor and targeted genetic testing can be done.

Once the tests have been conducted, they require interpretation:

Pelvic ultrasound is used to check the presence or absence of a uterus and internal sex organs. The absence of the uterus could indicate conditions like Müllerian agenesis or another condition known as Disorders of Sex Development (DSD). Various other useful information could be discovered with this test.

With serum tests, pregnancy can be ruled out first, since women can get pregnant before their first period. Checking the levels of FSH and estradiol can help distinguish between issues in the brain (hypothalamus and pituitary gland) or the ovaries themselves. The levels of other hormones like TSH, estradiol, and prolactin can provide information about thyroid disease, various tumors, and other conditions. Other tests can also detect chronic illness.

Bone age radiography can give insight into the impact of sex hormones on bone maturation, and provides information about future growth potential. It can also help doctors provide appropriate counseling around predicted adult height.

The results of all these assessments help doctors identify the most common causes of primary amenorrhea:

• Gonadal dysgenesis or Premature Ovarian Insufficiency (POI)
• Müllerian agenesis
• Transverse vaginal septum
• Imperforate hymen
• Constitutional delay of growth and puberty (CDGP)
• Functional hypothalamic amenorrhea (FHA)
• Polycystic ovary syndrome (PCOS)
• Complete androgen insensitivity syndrome (CAIS)

In conclusion, understanding the causes of primary amenorrhea, which can involve both clinical examination and various diagnostic studies, is crucial for proper patient management and treatment.

Treatment Options for Primary Amenorrhea

Primary amenorrhea, which refers to the absence of menstruation in a girl by age 15, needs treatment aimed at addressing the root cause and preventing potential complications. Some of these root causes might be abnormalities in the genital tract or disorders affecting a part of the brain called the hypothalamus, pituitary, or the gonads (ovaries).

Let’s talk about some specific types of root causes and how they’re managed:

Abnormalities in the genital tract, such as blockages in the vagina or cervix, can usually be treated with surgery. However, these patients might have ongoing issues like pelvic adhesions (scar tissue) or endometriosis (when tissue similar to the lining of the uterus grows in other areas). Some patients with congenital anomalies affecting the vaginal length may consider various treatment options, including surgical techniques or conservative ones like using vaginal dilators. In cases where the patient has a Y chromosome and undeveloped gonads, these should be removed due to the high risk of cancer. All these patients should also receive emotional support and counseling, and information on available support groups.

Patients with disorders that affect the hypothalamus, pituitary or the gonads might lack sex hormones required for menstruation. In this case, they might need to see an endocrinologist for hormone therapy. This therapy not only aims to stimulate menstruation but also to protect their bone and cardiovascular health. Dietary supplements such as calcium and vitamin D, along with routine exercise, are also recommended to maintain bone health. In some cases, patients might need contraceptive management as well. Additionally, these patients should be screened for other related conditions like hypothyroidism.

For patients with a type of amenorrhea known as Functional Hypothalamic Amenorrhea (FHA), due to factors like low body weight, stress, or eating disorders, the primary treatment involves reversing these factors. This might include gaining weight, reducing stress, making lifestyle changes, and meal planning. Therapies such as cognitive-behavioral therapy might be recommended for those with severe stress.

Other possible causes of primary amenorrhea include tumors that produce prolactin, a hormone responsible for milk production. The first-choice treatment for this condition is a type of medication called a dopamine agonist. However, larger tumors might need surgery.

Patients with other hormonal abnormalities causing amenorrhea should be treated by addressing the root cause. This might involve lifestyle changes, medication, or both. For example, patients with Polycystic Ovary Syndrome (PCOS) might be recommended to adopt a healthy diet and exercise program, and also take medication to prevent complications such as abnormal uterine growth and acne.

Finally, in cases where amenorrhea is caused by medication or certain physiological events like pregnancy or breastfeeding, it usually resolves when the event ends or the medication is stopped. However, the decision to change medication should be made after considering the benefits and risks.

What else can Primary Amenorrhea be?

Amenorrhea, or the absence of menstrual periods, is actually a symptom of an underlying condition. There are numerous potential causes that could be at the root of amenorrhea. These could include:

• Normal bodily processes or the result of certain treatments:
  • Pregnancy
  • Breastfeeding
  • Menopause
  • Medications, chemotherapy, or radiation treatments
• Issues with the hypothalamus and pituitary gland, such as:
  • Normal variations in puberty development
  • Stress-induced lack of periods
  • Prolactinoma or other hormone-secreting pituitary tumors
  • Kallman syndrome, a genetic condition
  • Damage to the pituitary gland
  • Autoimmune diseases
  • Empty sella syndrome, a condition where the pituitary gland shrinks or flattens
• Ovarian conditions, such as:
  • Primary ovarian insufficiency
  • Gonadal dysgenesis, a disorder affecting sex organ development
  • Autoimmune diseases
  • Enzyme deficiencies affecting hormones
• Other hormonal imbalances:
  • PCOS or other causes of high male hormone levels
  • Hormone-producing ovarian or adrenal tumors
  • Thyroid disease
  • Uncontrolled diabetes
• Abnormalities with the reproductive tract, such as:
  • Complete or partial lack of uterus and vagina development
  • A condition where the tissue typically seen in the inner womb lining grows outside the uterus
  • Scarring of the womb due to surgery or trauma
  • Narrowing of the cervix
  • Failure of the vagina to form properly
  • A blocking wall across the vagina
  • An imperforate hymen, blocking the vagina

Each of these potential causes would require different treatments, so it’s important to figure out the exact cause in order to treat amenorrhea effectively.

What to expect with Primary Amenorrhea

The outlook for primary amenorrhea (when a girl does not start her period by age 15), relies on the root cause, which is not extensively discussed in this document. However, generally speaking, causes of primary amenorrhea that can be reversed or are temporary, such as Chronic Disease Puberty (CDPG) and Functional Hypothalamic Amenorrhea (FHA—when a woman’s period stops due to intense physical or emotional stress), usually have a better outlook than those linked to the ability of the ovaries to function, like gonadal dysgenesis (when the ovaries can’t produce the usual amounts of sex hormones).

The chance of having children in the future varies importantly, depending on the cause. For female athletes or individuals with CDPG, who have functional hypogonadotropic hypogonadism (a condition where the body doesn’t produce enough sex hormones), the chances of having children are basically normal when the Hypothalamic-Pituitary-Ovarian (HPO) axis (a system in the body that regulates a woman’s menstrual cycle) begins to work properly. However, for patients with gonadal dysgenesis or premature ovarian insufficiency (POI; when a woman’s ovaries stop working before age 40), the chances are much lower. For patients with müllerian agenesis (a rare disorder that affects the development of a woman’s reproductive system), the best option for having a child is typically using a surrogate carrier to carry the pregnancy.

Possible Complications When Diagnosed with Primary Amenorrhea

Complications can occur in relation to specific health conditions such as long-term low levels of estrogen or uncontrolled estrogen. These complications might include:

• Hot flashes
• Bone fractures due to osteoporosis
• The thickening of the uterine lining, known as endometrial hyperplasia
• Diseases related to metabolism and the heart
• Infertility
• Leaking milk-like substance from the breasts, known as galactorrhea
• Effects of high levels of male hormones, such as developing male characteristics, excessive hair growth, and acne
• Mental health issues such as anxiety and depression

Preventing Primary Amenorrhea

It’s important for women to understand that having a regular menstrual cycle is a good sign of overall health, particularly for those who are of childbearing age and not on any hormonal medication. If a woman stops having periods, it could signal a serious underlying health condition that should be investigated.

Maintaining a healthy lifestyle is also key. This includes eating a balanced diet, getting regular exercise, and taking care of mental health. During regular check-ups with doctors, women should also be given guidance about what to expect at various stages of their reproductive lives, such as when to expect the onset of puberty, what the average age for menopause is, what physical changes to anticipate, and discussing contraception methods, if interested.

Additionally, women should also be educated about their menstrual cycle. This includes knowing how to track their cycle from the start of one period to the start of the next, understanding what the average length of a cycle should be, and being able to identify when a cycle seems abnormal. This knowledge will not only help doctors detect any health problems sooner but will also ease any anxiety a woman may feel about what changes to expect during significant life transitions like puberty and menopause.

Doctors can introduce helpful tools for tracking menstrual cycles, and patients should be encouraged to use these tools to stay informed about their reproductive health.