Amenorrhea

What is Amenorrhea?

A woman’s menstrual cycle can change throughout different stages of her life, such as puberty or menopause. These changes could be due to various factors and may be perfectly normal or a sign of serious health issues. Some women may experience long gaps between their periods during such phases, and doctors may sometimes be uncertain about the right tests to order or whether an evaluation is needed.

Amenorrhea is a condition where a woman of reproductive age doesn’t have her menstrual period. It could be primary amenorrhea, where a girl hasn’t had her first period by the age of 15 or within three years after her breasts start to develop. It could also be secondary amenorrhea, where a woman who used to get her period regularly stops getting it for more than three months, or any woman who had at least one spontaneous period stops getting it for more than six months. Women with either type of amenorrhea should have an evaluation. In case a teenager hasn’t developed breasts and still doesn’t have her period by 13, she should be evaluated for the possibility of late puberty.

Amenorrhea can be caused by a variety of issues, which could include problems with outflow of the menstrual blood, failure or deficiency of the ovaries, disorders of the hypothalamus or pituitary gland in the brain, other endocrine gland disorders, or due to physiological reasons or certain medications. When evaluating a patient with amenorrhea, doctors usually follow a systematic process to identify the potential underlying causes. They may take a detailed history and conduct a full physical examination, a urine pregnancy test, blood tests to assess hormone levels, and imaging such as ultrasound of the pelvis. Additional tests may also be carried out depending on the symptoms. Treatment essentially depends upon the underlying cause and may include changes in lifestyle, hormone therapy, medications, surgery, or mental health services.

What Causes Amenorrhea?

For a woman to have her period, four different body parts need to work properly: the hypothalamus (part of the brain), the anterior pituitary gland (another part of the brain), the ovaries, and the genital outflow tract, which includes the uterus, cervix, and vagina. If any of these parts aren’t working correctly, a woman cannot have a period. It’s essential to figure out why a woman isn’t having her periods because this will determine the best treatment.

Physical blockages or problems can prevent the development of the lining of the uterus (the endometrium) or block the flow of menstrual fluid out of the body. This could be due to a variety of conditions, some of which may be present from birth, others might develop later in life. For example, it could be due to the absence of certain female reproductive structures (like the uterus or vagina), an unresponsive reaction to androgens, or other conditions that cause the development of scar tissue or blockages.

Sometimes, the problem with having periods doesn’t come from the reproductive organs but results from conditions affecting the hypothalamus or pituitary gland. These parts of the brain are responsible for controlling the menstrual cycle. If they aren’t functioning correctly, this can result in too low levels of certain hormones (FSH and LH), leading to a disruption in ovulation and periods. Such disruptions can occur due to conditions like functional hypothalamic amenorrhea (FHA), too much prolactin in the blood (hyperprolactinemia), disorders affecting puberty, or damage to these parts of the brain.

Functional hypothalamic amenorrhea is a condition where because of an imbalance in energy, the hypothalamus suppresses the body’s reproductive cycle. This could be due to an underlying eating disorder, excessive exercise, or extreme stress. Other inflammation, injuries, chronic diseases, or serious illnesses can also lead to this type of amenorrhea.

One of the most common causes of periods not occurring is a group of conditions known as “gonadal disorders”. Gonadal disorders happen when the ovaries aren’t working properly and producing enough estrogen and progesterone. The lack of these hormones can result in the absence of periods.

Other hormonal disorders that can lead to periods not occurring often include polycystic ovary syndrome (PCOS), a condition that can result in high levels of male hormones in the body and cysts on the ovaries. Less common causes include conditions that lead to overproduction of androgens, tumors, and Cushing syndrome.

Physiologic amenorrhea is a natural absence of menstruation that occurs during pregnancy, breastfeeding, or menopause. During these times, hormonal transformations make it normal not to have periods.

Certain medications can also cause amenorrhea, including hormonal contraceptives, antipsychotic drugs, and some cancer treatments. It’s also worthwhile to note that women can experience menopause (the natural end of the reproductive years) in their 40s or 50s, which is considered normal. The decline of ovarian function during menopause leads to significantly decreased production of estrogen and progesterone, ultimately causing periods to stop.

Risk Factors and Frequency for Amenorrhea

In the US, only around 2% of teenage girls have not started their period by the age of 15. The main reasons for girls not starting their periods, also known as primary amenorrhea, include issues with the ovaries (43% of cases), absence of the uterus (10% to 15% of cases), and delayed puberty (14% of cases). Half of the people with primary amenorrhea have abnormal chromosome arrangements, in the absence of other diseases.

Secondary amenorrhea, which is when periods stop for non-physical reasons, affects around 3 to 4% of women of childbearing age. The most frequently seen causes of secondary amenorrhea involve problems such as Polycystic Ovary Syndrome (PCOS), Functional Hypothalamic Amenorrhea (FHA), increased levels of prolactin, and Primary Ovarian Insufficiency (POI). Approximately 13% of women under the age of 30 with secondary amenorrhea not due to physical causes have an abnormal chromosome arrangement.

Signs and Symptoms of Amenorrhea

Amenorrhea is a condition where a woman in her reproductive years doesn’t experience a menstrual period, and it can be due to an underlying health issue. It is grouped into two types: primary or secondary amenorrhea. Primary amenorrhea affects girls who have never had their periods by the age of 15 or within three years of beginning breast development. Secondary amenorrhea, meanwhile, occurs in women who have had at least one menstrual cycle but then stop menstruating for three months or more if they previously had regular cycles, and for six months or more if they had irregular cycles.

For teenagers who are 13 years old with primary amenorrhea and haven’t undergone breast development, evaluation for delayed puberty is necessary.

Knowing the detailed medical history of patients with amenorrhea is very important in diagnosing the main cause. Information such as the date of the last menstrual period, the beginning of breast and sexual hair development, previous menstrual patterns, and general health state help in identifying the condition. Knowing the patient’s lifestyle, current medications, and any history of extreme weight loss or persistent illnesses is also crucial.

• Sexual history and pregnancy symptoms
• Lifestyle factors indicating FHA(like restrictive diets or vigorous exercises)
• Galactorrhoea or medications associated with hyperprolactinemia
• Symptoms of hypothalamus or pituitary gland diseases like vision changes or headaches
• Symptoms indicating hypoestrogenism like hot flashes or night sweats
• Symptoms of hyperandrogenemia(including male-pattern hair growth or excessive acne)
• History of metabolic or endocrine diseases
• Symptoms of autoimmune or other chronic diseases
• Uncontrolled diabetes symptoms

As part of the diagnostic process, physicians will also look for physical signs that might suggest the cause of amenorrhea. Some of the signs related to different causes include low body mass index, subtle changes in vision, abnormal breasts discharge, high blood pressure, a mass in the lower abdomen, changes in skin or hair related to androgens or thyroid disorders, and any abnormalities in the genital area. However, these signs present on their own might not be enough for a diagnosis, and they should be considered along with the patient’s medical history.

Testing for Amenorrhea

If you have been experiencing missed periods (known as amenorrhea), doctors usually perform several tests for initial diagnosis. These can include a urine pregnancy test; a test for levels of FSH, LH, and estradiol (hormones involved in the menstrual cycle); a test for prolactin (another hormone); a test for thyroid-stimulating hormone (TSH), which can impact your menstrual cycle if your thyroid isn’t working correctly; and a pelvic ultrasound to look at your reproductive organs.

Depending on results and your unique circumstances, the doctor may order additional tests. For instance, if the doctor suspects high levels of androgens (male hormones), they might test testosterone levels and other related hormones. For younger patients with overall delayed puberty, they may look at bone age and growth hormone levels. If you have certain longstanding, chronic diseases, additional blood tests might be needed.

If conditions like premature ovarian failure or Turner syndrome are suspected, a karyotype exam (a test that looks at the number and shape of all your chromosomes) or a pelvic MRI (a detailed image of your pelvic area) might be used. If a brain condition is possibly causing your symptoms, a CT scan or MRI of the brain could be needed. If genetic issues are suspected, you may be referred to a genetic counselor for specialized testing.

Test results will be then interpreted by your doctor. For instance, a positive pregnancy test would confirm you’re pregnant. Abnormal TSH could indicate a thyroid issue, while high prolactin levels could suggest a condition called hyperprolactinemia. Low levels of FSH and estradiol might hint at an issue with brain signaling to your ovaries. High FSH and low estradiol levels may suggest an issue with ovarian function. Abnormal readings for other types of tests could point to specific conditions or issues that your doctor would discuss with you.

A pelvic ultrasound could reveal structural abnormalities, such as an imperforate hymen (a membrane that obstructs your vagina). It can also give signs about hormone exposure — a thin endometrial stripe (the lining of the uterus) might suggest low estrogen.

Treatment Options for Amenorrhea

The treatment for amenorrhea depends on the root cause of the condition and how a patient’s body responds to it.

Blockages in the Outflow Tract

For certain blockages, such as an imperforate hymen or cervical stenosis, surgery can remove the obstruction. However, these patients can still have ongoing discomfort, including endometriosis and pelvic adhesions. Individuals born with problems affecting the length of the vagina who want to have intercourse, can choose from several options, including surgery or non-surgical approaches (for example, vaginal dilators). It’s important to note that non-surgical management works well in 90-96% of patients. However, patients with these conditions need to consult with specialists who can provide the right treatment plan. Support and counseling can also be very helpful, as they address potential emotional and psychological issues.

Issues with the Hypothalamus, Pituitary Gland, and Gonads

Patients of typical reproductive age who lack sex hormones (like in POI or Kallman syndrome) need hormone therapy to protect their bones and heart health. Daily intake of vitamins and minerals, along with regular weight-bearing exercises, can also help maintain their bone density. A small percentage of patients with POI can still have children and may want to prevent pregnancy. In these cases, contraceptives can be used. But patients need to know about the increased risk of blood clots, which can occur in any contraceptive method. Regular checks for other health conditions, like hypothyroidism, are also necessary as they can often occur alongside these disorders.

The main treatment for amenorrhea caused by FHA is to deal with the factors causing the condition. This could include gaining weight, reducing stress, and changing the way a person lives and eats. If a patient has FHA because of an eating disorder, they may need education and counseling to handle the physical and psychological aspects of their condition. Keeping a healthy weight and eating properly are the main ways to keep this type of amenorrhea in check. However, combined hormone contraceptives alone are not recommended for treating amenorrhea. Cognitive Behavioral Therapy (CBT) is also seen as an effective way to deal with FHA due to severe stress.

Cabergoline, a type of dopamine agonist medication, is generally the first choice of treatment for patients with a tumor that secretes prolactin. Larger tumors of this type can also be treated with surgery. If amenorrhea is caused by certain medications, the best treatment is typically to stop using those medications. If that’s not possible, a dopamine agonist might be used with caution.

Other Hormonal Issues Affecting the HPO Axis

For patients with other endocrine abnormalities (like PCOS or diabetes), the main focus should be on improving the condition causing amenorrhea. In some cases, lifestyle changes, such as maintaining a healthy diet and regular exercise, can be the most beneficial treatment. In contrast, other disorders may require medication. Certain drugs can also help treat complications that can arise from these conditions, like combined hormonal contraceptives, which can prevent the growth of endometrial hyperplasia and cancer. Regular checks for high blood pressure and excessive weight are also important, as well as screenings for dyslipidemia and impaired glucose tolerance every three to five years.

Physiological and Medication-Induced Amenorrhea

In cases where amenorrhea is caused by physiological events or medications, it usually goes away once the event is over or the medication is stopped. Before changing any medications, it’s important to weigh the pros and cons. Medication-induced hyperprolactinemia is often treated by discontinuing the medication causing it. However, if that’s not possible, a dopamine agonist might be used with caution.

What else can Amenorrhea be?

Amenorrhea isn’t a disease itself, but a symptom of several underlying medical conditions. When a patient experiences amenorrhea, doctors would look into various possible reasons including:

Physiological and Drug-Induced Reasons

• Pregnancy
• Women that are breastfeeding
• Menopause
• Impact of certain medicines, chemotherapy, or radiation

Regarding the Hypothalamus and Pituitary Gland

• Delayed puberty
• Lacking or irregular periods tied to rigorous exercise, stress, or low body weight
• Abnormal growths or tumors in the pituitary gland that affect hormone levels
• Kallman syndrome, a condition that can result in a lack of sense of smell and late or absent puberty
• Destruction of pituitary gland tissue
• Autoimmune conditions
• Empty Sella Syndrome – a condition where the pituitary gland shrinks or becomes flattened

Ovarian Conditions

• Premature ovarian insufficiency (early menopause)
• Streak ovaries, when normal ovarian tissue is replaced with underdeveloped tissue
• Autoimmune diseases
• Conditions that affect the body’s ability to produce estrogen

Other Hormonal Disorders

• Polycystic ovary syndrome (PCOS) which results in high levels of androgens (male hormones)
• Certain types of tumors in the ovaries or adrenal glands that could affect hormone production
• Thyroid problems
• Uncontrolled diabetes

Conditions Affecting the Reproductive Tract

• Incomplete development of the uterus and vagina
• Androgen Insensitivity Syndrome, a condition where a genetic male is resistant to male hormones and has some or all of the physical traits of a woman
• Scarring or adhesion within the uterus
• Narrowed or blocked cervix
• Abnormal development of the vagina
• Presence of a horizontal wall within the vagina
• Imperforate hymen – a hymen that completely closes the vagina

What to expect with Amenorrhea

The outlook for a condition often depends on the root cause. In depth discussions about this can be found within articles focused on each individual cause. It’s important to consider aspects associated with both general health and fertility. Generally, causes that can be fixed through surgery (for example, an imperforate hymen, which is a condition where the tissue usually covering the vaginal area is not properly opened) or fully reversed (for example, FHA or Functional Hypothalamic Amenorrhea, which is a condition where the menstrual cycle stops due to the brain’s signal to the female reproductive system) typically have a great outlook.

Possible Complications When Diagnosed with Amenorrhea

There can be various complications due to certain underlying conditions such as a chronic state of low estrogen or uncontrolled estrogen. These complications can include:

• Hot flashes and night sweats (vasomotor symptoms)
• Bone fractures due to reduced bone density (osteoporotic fractures)
• Thickening of the lining of the uterus (endometrial hyperplasia)
• Metabolic and cardiovascular diseases
• Difficulty in conceiving (infertility)
• Milk production from the breast not related to childbirth (galactorrhea)
• Excessive male hormones leading to masculine physical traits (hyperandrogenism, such as virilization, excess body hair, and acne)
• Mental health issues, like anxiety and depression (psychological effects)

Preventing Amenorrhea

It’s important for women who are of reproductive age and are not using hormonal medicines to understand that having a regular menstrual cycle is a normal and healthy part of life. If a woman stops having her period, it might be a sign of a serious health condition, and she should check with a healthcare professional.

Living a healthy lifestyle is also key to menstrual health. This includes eating a balanced diet, doing the right amount of exercise, and taking care of one’s mental well-being. Doctors should always talk about these aspects including the changes a woman can expect during her reproductive years, during every health check-up. This could include explaining when puberty and menopause typically happen, what physical changes are normal, and discussing a woman’s family planning ideas.

Learning how to track a menstrual cycle can also be very helpful for women. This involves noting down the first day of one period and then the first day of the next period, keeping track of the average time between cycles, and knowing what is considered not normal for a menstrual cycle. This knowledge can help identify health issues earlier, can alleviate worry over normal changes like puberty and menopause, and it also assists women in better understanding their body. There are many useful tools available that can help women easily keep track of their menstrual cycles.