EARLY MENOPAUSE

To diagnose menopause, you must not have had a period for the past year, meaning you should not have had any bleeding, including spotting, for 12 consecutive months. The average age for menopause is in the 50s. Early menopause, on the other hand, refers to experiencing this entire process in your 20s or 30s, before the age of 40.

There are various terms used instead of early menopause (surgical menopause, premature ovarian insufficiency, menopause caused by radiation and chemotherapy, menopause due to genetic disorders, etc.). In this article, I will discuss the risk factors, causes, diagnostic tests, and treatments for early menopause.

Risk Factors for Early Menopause

It’s not always clear which women will experience early menopause, but certain conditions can negatively affect ovarian reserves and bring on menopause earlier. Those with predisposing conditions are at a higher risk of early menopause. Here’s a summary of factors that contribute to early menopause:

• Family history of early menopause
• Genetic conditions (such as Fragile X syndrome)
• Conditions that damage the ovaries (such as ovarian cysts, pelvic infections)
• Frequent ovarian surgeries
• Undergoing chemotherapy or radiotherapy that may harm the ovaries
• Taking medication that could damage the ovaries
• Smoking

Causes of Early Menopause

There are many known or unknown causes of early menopause. For example, you may have undergone surgery to remove your ovaries, there may be a family history of early menopause, or your ovaries may have been damaged due to chemotherapy or radiotherapy. In such cases, the cause is evident.

However, sometimes there is no identifiable cause, and you find yourself facing the process of early menopause. You may enter a period where you wonder, “Why me?”

In this section, I will discuss possible risk factors for early menopause.

The most common known causes of early ovarian insufficiency are as follows:

• Medical conditions such as post-surgery, post-radiotherapy, or post-chemotherapy
• Chromosomal and genetic abnormalities
• Autoimmune diseases (autoimmune conditions)
• Environmental factors (viruses, chemicals, etc.)
• Metabolic conditions (type 1 diabetes, galactosemia, etc.)
• Endometrioma (chocolate cyst)

Autoimmune Diseases

Autoimmune diseases occur when the body’s immune system attacks its own cells. In some autoimmune diseases, the body sees the ovaries as a threat and sends immune system cells to attack them, resulting in ovarian damage. The ovaries cannot produce hormones or eggs as they used to, leading to ovarian insufficiency.

Depending on the source, 5-30% of cases of primary ovarian insufficiency are believed to have an autoimmune cause.

[alert-warning]Certain autoimmune diseases associated with excessive immune activity can cause early menopause by attacking the ovaries. Examples include Addison’s disease, Graves’ disease, among others.[/alert-warning]

Chromosomal Disorders

Some genes in the body play a role in egg formation and hormone secretion. Diseases associated with defects in these genes can lead to an earlier onset of menopause. Studies indicate that 10-12% of women diagnosed with early menopause have chromosomal abnormalities. This condition is more common in diseases associated with X chromosome abnormalities (94%).

Turner Syndrome (46,X0): It is characterized by the absence or abnormality of one of the two X chromosomes that women should have.

Fragile X Syndrome:

If you are a carrier of fragile X syndrome, you may carry fewer eggs in your ovaries, which can lead to early menopause.

It is one of the most common causes of familial mental retardation. The incidence is about 1/4000-1/6000 in women.

Infections

Some infections such as tuberculosis, malaria, measles, can damage ovarian tissue, disrupt ovarian hormone secretion, and damage ovarian tissue and eggs, leading to early menopause.

Surgical Interventions

Oophorectomy is the surgical removal of the ovaries.

Surgical menopause (also known as bilateral oophorectomy) occurs when both ovaries are surgically removed, leading the body into menopause. In other words, the ovaries do not stop functioning gradually, as in the natural process; instead, they are removed suddenly, and the body enters menopause.

In most cases, the procedure is minimally invasive, meaning a surgeon makes small incisions to access and remove the ovaries in the lower abdominal area.

Sometimes, your doctor may perform an oophorectomy during a hysterectomy (uterus removal surgery), meaning your ovaries may also be removed.

There are several reasons why your doctor may perform an oophorectomy that leads to menopause. These include:

Endometriosis (having chocolate cysts in your ovaries)

Non-cancerous ovarian tumors or cysts

Ovarian cancer

Ovarian torsion (twisting of the ovary around itself, disrupting blood flow)

Some women choose to undergo preventive surgery in cases of genetic disease to reduce the risk of ovarian or breast cancer.

Women with a family history of ovarian or breast cancer are at a higher risk of developing these cancers. Some genetic conditions predispose individuals to ovarian and breast cancer. Among these genes, BRCA is prominent. Some women undergo genetic testing to determine if they have mutations in the BRCA1 and BRCA2 genes.

[alert-warning]Approximately 60% of ovarian cancer patients with a genetic predisposition are associated with BRCA1 mutations and 30% with BRCA2 gene mutations.[/alert-warning]

Surgical menopause has a significant difference in that the patient enters menopause immediately after surgery, without experiencing the perimenopausal period.

According to the American National Cancer Institute, mutations in the BRCA1 and BRCA2 genes account for 15% of all ovarian cancers. These gene mutations also account for 20 to 25% of hereditary breast cancers. Women with these genes are at a higher risk of developing cancer at an earlier age. In such cases, removing the ovaries can reduce a woman’s risk of developing the disease. If your BRCA test result is positive, meaning you have this gene, talk to your doctor and seek genetic counseling.

Radiation Therapy and/or Chemotherapy

Chemotherapy drugs or radiation given for treatment can damage not only cancer cells but also rapidly dividing cells such as hair follicles, bone marrow, and eggs, leading to conditions such as hair loss, suppression of the immune system, and early menopause. In some cases, temporary menopause may occur due to low-dose short-term treatment. After treatment, the ovaries may stop functioning for several months but may eventually recover. If the egg reserve is damaged during this process, infertility may occur even if periods return.

Other Conditions Causing Menopause-Like Symptoms

Thyroid Disorders: The thyroid gland is an organ located in the neck. It regulates many functions in the body through the hormones it secretes. Deficiency or excess can lead to serious conditions and complaints. It can mimic early menopausal symptoms by causing amenorrhea (lack of menstruation).

Hyperprolactinemia: Prolactin hormone is known as the milk hormone. Its main function is to stimulate milk production from breast tissue after childbirth. The normal value in the blood is 10-25 ng/ml. When prolactin hormone is secreted inappropriately due to various reasons, it can cause irregular menstruation and even amenorrhea (lack of menstruation), mimicking this symptom of early menopause.

Polycystic Ovary Syndrome (PCOS): In a normal menstrual cycle, the ovary produces one egg each month, but in polycystic ovary syndrome (PCOS), there are numerous small sacs (follicles) containing unruptured eggs in the ovaries. Hormones secreted from these unruptured follicles can affect your overall hormone balance, causing amenorrhea (lack of menstruation) and mimicking early menopause. Other symptoms seen in PCOS include irregular menstruation, infertility, increased hair growth, hair loss, acne, increased risk of uterine and possibly breast cancer, increased risk of cardiovascular disease, increased risk of diabetes due to increased insulin hormone, depression, and anxiety.

While no causal relationship has been proven between smoking and early menopause, there is an association between smoking and early menopause. Therefore, women predisposed to POI should be advised to quit smoking.

• Pituitary gland disorders,
• Imbalance in body fat mass,
• Excessive stress,
• Excessive exercise,

Oral contraceptives, certain other medications, and systemic diseases can also cause irregular menstruation, mimicking early menopause.

Early Menopause Symptoms

During early menopause, there are changes in the body due to decreased estrogen hormone levels. These are often the symptoms that prompt you to see a doctor.

Let’s take a closer look at these symptoms you’re experiencing.

When a patient presents with complaints of amenorrhea, the doctor will first request blood tests to investigate thyroid hormones, prolactin, and some female hormones to rule out diseases that mimic early menopause.

Hot Flashes

Do you ever feel a sudden sensation of heat on your face while sitting quietly watching TV? Hot flashes are the most common symptoms of menopause. They can occur in 3 out of 4 women. Some patients may experience hot flashes even while continuing to menstruate during the perimenopausal period.

A hot flash is a sudden sensation of heat felt in the upper part of the body. Your face and neck may become flushed. Tiny red dots may appear on your chest, back, and arms. You may even experience sudden chills or sweating after hot flashes.

This condition is very common a year before and after the cessation of menstruation. Recent scientific studies have shown that hot flashes can last up to 14 years after menopause.

Vaginal Dryness and Infection

Problems such as vaginal dryness and infection may begin or worsen during the menopausal period. As mentioned earlier, low levels of estrogen hormone during menopause cause the vaginal tissue to become drier and weaker. This can lead to itching, burning, or pain during intercourse.

You may develop small tears in the vagina during sexual intercourse. Vaginal tears put you at higher risk for sexually transmitted infections (STIs or STDs). Therefore, although you have no risk of pregnancy after menopause, you should still practice safe sex to prevent sexually transmitted diseases.

Irregular Periods

You might be thinking, “I’m already in menopause, why do I need periods?” However, due to hormonal fluctuations in your blood during the perimenopausal period, it is very likely that you will experience irregular menstrual bleeding and spotting. Your periods may become more frequent or less frequent. They may last longer or shorter. Missing a few periods without any symptoms does not mean you are in perimenopause or transitioning to menopause.

Sleep Problems

Many women experience difficulty sleeping throughout menopause. You may have difficulty falling asleep and your sleep quality may be affected due to the decrease in progesterone hormone in your body. In addition, decreased estrogen hormone levels in your blood can cause hot flashes during sleep. This is sometimes called night sweats. Many menopausal women experience symptoms related to urination. If frequent urination is added during sleep, you may feel tired throughout the day.

Depression and Anxiety

During menopause, your risk of depression and anxiety is higher. A new process can raise questions and concerns in your mind. You may experience sadness or depression due to the loss of fertility or changes in your body. If you have symptoms of depression or anxiety, you should definitely talk to your doctor. Your doctor may recommend therapy or medication or both for depression or anxiety treatment.

Mood Swings

You may feel irritated or have sudden crying spells out of nowhere. Just as you experienced mood swings before or during your menstrual periods, it is more likely that you will experience emotional changes during menopause as well. Also, even if you have never experienced these complaints before menstruation or after childbirth, you may experience them during menopause. These emotional fluctuations may also be due to stress, changes in family dynamics, and feeling tired. These emotional fluctuations do not necessarily mean depression.

Skin

Due to the lack of estrogen after menopause, changes such as dryness, loss of elasticity, and decreased blood flow occur in the skin, resulting in thinning and wrinkling. These changes can also result in poor wound healing, hair loss, and pigmented spots (pigment changes) on the skin. The good news is that all of these can be delayed with estrogen therapy. Wrinkles, smoking, and sun exposure exacerbate these symptoms. You should avoid smoking and sun exposure.

Hair

Unwanted changes in hair and hair include hirsutism (unwanted facial hair) or alopecia (hair loss). Hair loss is the most common. Hair loss has also been reported on the lower legs, genital area, and armpits. Oral Hormone Replacement Therapy (HRT) may help control increased facial hair growth in some women.

Hair removal creams, epilation, and waxing can be effective treatments for increased hair growth. Hair loss can be treated with locally applied minoxidil, but you should always consult your doctor before using any medication.

Teeth

Menopause can be blamed for a variety of dental and oral problems, including dry mouth and gum inflammation.

HRT can be beneficial as a result of its role in preserving bone and preventing tooth loss and eliminating the need for prosthetics. The effects of HRT include reduced gum bleeding, decreased bone loss, and improved saliva flow.

Investigative Tests for Early Menopause

So, you’ve noticed some symptoms and are wondering, “Could I be experiencing early menopause?” What happens now? How can you determine whether it’s early menopause or another condition causing these symptoms? The only way to be sure is to consult your doctor.

Shall we take a brief look at the tests that need to be done?

Hormone Tests

Follicle Stimulating Hormone (FSH)

This hormone is the most helpful in diagnosing menopause in patients under 45 years old. Let’s take a somewhat technical approach to FSH. What does FSH do? Why does it increase in early menopause? Let’s take a closer look.

FSH is a hormone secreted by the pituitary gland in the brain. The pituitary gland produces FSH and releases it into the bloodstream. This hormone (yes, it’s quite a journey) travels through the blood to the ovaries, where it stimulates the follicles, or egg cells, present in the ovarian tissue, allowing you to ovulate and become pregnant each menstrual cycle. If the ovaries respond less to FSH (during early menopause when the ovaries are not functioning properly), the body releases more FSH to obtain the same number of eggs. More FSH stimulates the ovaries to ovulate as before. Therefore, an increase in FSH levels is an indirect indicator that the ovaries no longer function as they used to.

Interpreting Your FSH Result

On the 3rd day of the menstrual cycle, the normal FSH value is expected to be 3-10 mIU/ml. Results between 10-12 mIU/ml indicate that your ovaries are starting to slow down. In other words, you may be in the perimenopausal period (the period when you start to feel physical symptoms but have not yet experienced a year of amenorrhea).

Higher FSH values – 30 and above – are considered indicative of menopause. Even if your FSH levels are high, you may still be menstruating.

It should be noted that normal laboratory values may vary depending on the laboratory where the test is conducted.

Hormone levels can fluctuate, and blood values can fluctuate, so remember that a single independent FSH test may not mean much on its own!

Some women may have a high FSH value once and return to normal levels the next month. Here, what’s important is the increased FSH levels in blood samples taken 4-6 weeks apart.

Estrogen (Estradiol) Hormone

Estradiol is the most active form of estrogen hormone and is found in high levels in the blood during the reproductive years. It is secreted by the ovaries. As the ovaries begin to function more slowly with the onset of menopause, the estradiol level in the blood begins to decrease. The main cause of symptoms such as vasomotor symptoms, hot flashes, vaginal dryness, urinary tract complaints, depression, and diseases such as cardiovascular disease and osteoporosis during menopause is the decrease in estradiol hormone.

Interpreting Your Estradiol Result

The normal 3rd-day estradiol value is 25-75 pg/ml (these levels may vary from laboratory to laboratory). Generally, estradiol levels of about 30 or below are considered indicative of menopause, correlated with high FSH levels. If your estradiol level is less than 50 picograms per milliliter, you may still be menstruating, but you may also experience hot flashes, vaginal dryness, and difficulty sleeping.

In general, it is recommended to increase estradiol levels to at least 40 to 50 pg/mL to prevent bone loss, with the ideal being a value of 60 pg/mL or higher.

Antimüllerian Hormone (AMH)

Since AMH is secreted by cells called granulosa that surround egg cells, it is an indicator of how many eggs you have in your ovaries.

AMH levels are significantly lower in women with POF than in healthy women. AMH measurement also gives your doctor an idea of how you will respond to the drugs used in your treatment for childbearing desires. Studies have shown that patients with very low AMH values are more likely to experience amenorrhea (no longer menstruating), while patients with high AMH values are more likely to continue menstruating.

AMH can also be used to assess ovarian reserve before treatment in patients who will undergo chemotherapy or radiotherapy or who will undergo early menopause for medical reasons, also known as iatrogenic, after medication or surgery.

Other Tests

We have discussed the causes of early menopause and conditions that can mimic early menopause. While your doctor may request some tests to diagnose early menopause, they may also request other tests, in addition to those mentioned above, to investigate other possible causes and the effects of this process on your body.

Additional Tests That May Be Requested:

• Prolactin, TSH, Cortisol, ACTH, DHEA-S in blood samples
• Chromosome Analysis
• Pelvic Ultrasound and Breast Ultrasound
• Bone Density Measurement

Health Issues Caused by Early Menopause

Infertility

One of the most devastating consequences of early menopause is loss of fertility. Currently, there is no effective way to stop egg loss or reactivate the ovaries. If there are no eggs left, there is little that can be done. Some women may appear to have eggs on ultrasound, but there is a possibility of not responding to normal hormonal signals and being unable to conceive with medical treatments. About 5-10% of women with early menopause will begin ovulating and become pregnant naturally. However, a large portion will not regain lost ovarian function and menstrual cycles. Unfortunately, hormone replacement therapy does not increase the number of eggs or the chance of pregnancy.

Don’t despair immediately. First, the remaining egg count should be evaluated. If your egg count is low, there are two options. If you don’t have a partner planning for a child, freezing your eggs is the best option. If you have a partner considering having children, you can plan for pregnancy naturally or through IVF treatment according to your doctor’s recommendation.

Bone Loss (Osteoporosis)

Early menopause can affect a woman’s calcium levels in the bones. In women, estrogen helps the body effectively absorb calcium. As a woman’s estrogen levels begin to decrease during menopause, there is a faster loss of calcium from the body. Osteoporosis, or as we commonly know it, bone loss, resulting from decreased bone density, is a major cause of disability, especially with advancing age, leading to fractures of the hip, wrist, and spine. Women with premature menopause are at even higher risk of osteoporosis. A healthy diet, regular exercise, and, if necessary, medication supplementation will be important for prevention. Regular monitoring of bone density in this situation is strongly recommended. The use of estrogen therapy will replace lost estrogen and slow bone loss, even leading to significant reduction in fracture risk in women.

Heart Diseases

Estrogen is a hormone that has a protective effect on vascular health and other heart diseases. After menopause, the protective effect of estrogen on heart and vascular health disappears, and women are more likely to develop heart and vascular diseases. Many studies have shown that women who experience early menopause are at increased risk of coronary heart disease compared to their peers.

Standard coronary risk factors such as serum cholesterol, blood pressure, and obesity increase during menopause, which is associated with an increase in coronary heart disease observed after early menopause.

Women in this situation are recommended lifestyle changes (such as quitting smoking, regular exercise).

Treatment Options for Early Menopause

After receiving a diagnosis of early menopause, the main condition to be determined is whether you want to have children. Your doctor will determine the treatment flow accordingly.

If you desire to have children, you should research egg freezing and IVF treatments. Additionally, hormone replacement therapy is necessary to prevent health problems due to decreased protective estrogen effects in the body.

Infertility Treatment

For many young women, fertility is only a possibility in the future, so making decisions to preserve fertility, especially after a diagnosis of early menopause, can be very difficult. Some women decide to remain childless. Others may try IVF or medications to increase decreased ovarian function.

Another situation is the need for surgical treatment or preservation of fertility before chemotherapy/radiotherapy. In such cases, it is urgent to start the egg/embryo freezing process focusing on the patient’s health. The most effective and established way to preserve fertility in young women is to freeze oocytes or embryos before starting treatment.

Factors to consider in such situations include whether the patient has passed adolescence, whether there is a period of 2-3 weeks before starting chemotherapy/radiation therapy, and whether the cancer is hormone-sensitive.

In patients undergoing radiation therapy (radiotherapy), it may be considered to move the ovaries (oophoropexy) to an area outside the radiation field.

The decision to become pregnant when a woman is diagnosed with cancer or a serious medical condition is one that she should consider after consulting with her treating physician.

Hormone Replacement Therapy

Young women with early menopause may choose estrogen therapy to alleviate symptoms of estrogen deficiency, and often higher doses may be required compared to older women. The decision to use HT/HRT should be made after discussion with their doctor, as the presence of some diseases or cancers may preclude the use of estrogen therapy.

After breast or endometrial cancer, most women are advised to avoid estrogen-containing medications. In such cases, non-hormonal treatments for hot flashes or vaginal dryness may be beneficial.

When using HT/HRT, the current approach is to continue treatment until age 50-51, which is the average age of natural menopause. After this age, the decision to continue is similar to the decision for normal age menopause.

Options include estrogen tablets, estrogen patches, or gels. If a woman has undergone a hysterectomy (uterus removal surgery), estrogen alone can be used.

Additionally, regular vaginal estrogen can be used in patients experiencing problems during sexual activity.

Combined oral contraceptive pills (some birth control pills) can be used until age 50 if there are no significant risk factors for the woman (such as a tendency to clot, a history of clotting disease, or smoking). The decision to use combined oral contraceptive pills should be made after discussion with their doctor, as the presence of some diseases or cancers may preclude the use of estrogen therapy.

If contraception (birth control) is necessary and a woman does not desire pregnancy at the same time as treatment, hormonal options include combined oral contraceptive pills or an estrogen-containing intrauterine device (usually in the form of a patch or gel). Non-hormonal contraceptive options include the copper intrauterine device or barrier methods such as condoms.

Prevention of Osteoporosis

Osteoporosis, or bone loss due to estrogen deficiency, is common in women with early menopause. Smoking, inadequate calcium intake, and lack of exercise, as well as situations such as chemotherapy, also contribute to bone loss.

Especially if you are not using Hormone Replacement Therapy, estrogen hormone can no longer protect your bones.

Measuring bone density is very important. Depending on the basic bone density in your body, bone mineral density should be checked every one to two years.

A healthy lifestyle is important for maintaining bone health. Women with early menopause should not smoke, engage in regular weight-bearing exercise, and ensure adequate calcium and vitamin D intake.

If a woman has experienced a fracture due to osteoporosis at least once, there are many treatment options available to reduce the risk of possible recurring fractures.

Prevention of Heart and Vascular Diseases

Early menopause is closely associated with increased risk and cardiovascular disease, heart failure, and high cholesterol. If there are no obstacles to the use of Hormone Replacement Therapy, it is recommended to use it until the age of natural menopause. If you have risk factors for heart health, these risk factors (such as hypertension, weight, smoking, diabetes, cholesterol) should be screened appropriately. Lifestyle changes such as healthy eating, exercise, weight loss, and smoking cessation are as important as medication therapy during this process.

Cognitive Function

Chemotherapy-related memory impairment, one of the causes of early menopause, is well recognized. However, the long-term impact of estrogen deficiency on cognitive function is currently uncertain. Women who undergo early menopause due to surgical reasons have an increased risk of Parkinson’s disease and Alzheimer’s disease. Estrogen therapy until natural menopause age in women is believed to have a beneficial effect on cognitive/neurological conditions.

Lifestyle changes (exercise, quitting smoking, maintaining a healthy weight, safe alcohol intake) also play a significant role in improving these symptoms.