The Role of Hormones in Women’s Life

The role of hormones in women’s life is big. FHS, AHM, Prolactin, Hpophysis, Thyroid hormones should be controlled and treated when necessary.

How much does the FSH Hormone change with menopause and age?

In women, FSH hormone (Follicle stimulating hormone) is secreted from the pituitary gland in the brain and, as the name suggests, stimulates the follicles in the ovaries, making them grow. The follicles in the ovaries are small vesicles that carry the egg. Follicles grow under the influence of FSH hormone and ovulation occurs as a result of cracking under the influence of LH (Luteinizing hormone) in the middle period of menstruation. FSH hormone measurement is especially important in patients with menstrual irregularity and infertility problems.

The value of FSH in the blood is made on the 3rd day of menstruation (around 2-5 days). As the age progresses, ovarian reserve decreases and FSH rises. Especially after the age of 35, a gradual rise in the FSH is observed and this rise accelerates after the age of 40. Apart from age progression, conditions such as surgical removal of one or part of the ovaries or damage to the ovary in cyst surgery also cause an increase in FSH. Medications used or methods of contraception (birth control pills and other..) They do not cause the FSH to increase.

What should be the normal value of FSH in women?

It is considered normal for the FSH hormone value to be below 10 on the 3rd day of menstruation. It may be higher at other times of menstruation and the result may be misleading, so it should be measured especially at the beginning of the follicular phase, that is, in the first days of menstruation.

How many times does the FSH become difficult if it increases?

When the FSH hormone value rises above 10, the chance of getting pregnant may decrease. When FSH rises above 15, the problem of getting pregnant is become a problem. The greater the increase in FSH, the more difficult it is to achieve pregnancy. This applies both to spontaneous pregnancies and to pregnancies obtained by medications or in vitro fertilization. If the FSH is higher than 25, it is almost rare to achieve pregnancy with in vitro fertilization, either spontaneously or with treatment.

A point to note here is that the FSH may fluctuate in different months. For example, in the measurement made on the 3rd day of menstruation for a month, the FSH value may be low, ie high, and the FSH value may be low in the measurement made on the 3rd day of menstruation after 1-2 months. In this case, research has shown that the higher (poor) value is valid. In other words, the chance of pregnancy is low in these patients and the repetition measurements made after 1-2 months do not show that the chance of pregnancy increases even if the FSH is low. In such cases, FSH value and ovarian reserve can be evaluated more clearly with tests such as clomiphene citrate test.

Is it possible to reduce the value of FSH?

Some patients may search for what can be done to reduce the FSH value to increase the chance of pregnancy. An increase in FSH refers to a decrease in ovarian reserve with age, and like aging, this too cannot be reversed. As the age progresses, the number and quality of eggs decreases in the woman, and no medication or treatment (or herbal foods, drinks, teas) can restore the number and quality of eggs. In this case, what should be done is not to try to lower the FSH, but to try to achieve pregnancy with treatment before it rises further. Efforts other than this will cause the patient to lose time and the FSH to increase more in the meantime.

FSH is not the only value that shows the capacity of women to have children, that is, ovarian reserve. Apart from this, there are different analyzes and tests, methods.

In cases where FSH is very high, such as 25, pregnancy cannot be achieved spontaneously or with treatment or even with IVF. One option for these couples is adoption.

What is AMH hormone? When is it measured?

It is secreted at a high level by the Sertoli cells of the fetal testicle until puberty at the 8th week of gestation. For girls, it starts from 36 weeks of gestation. It is very low at birth, with minimal increase in the first 2-4 years. It is produced by granulosa cells of the pre-antral and antral follicles.

Advantages:

• It is the first marker that changes with age,
• The change between cycles is minimal,
• Can give information in every period of the cycle

A slight but statistically significant decrease in AMH levels was observed after ovulation. However, fluctuations in the early luteal phase are no more than measurement fluctuations between the two early follicular phases. Therefore, early luteal phase measurements can also be used clinically.

Where is the AMH hormone used?

Fields of usage:

• Determination of ovarian reserve (general population, before ovulation induction in infertile patient, before and after cancer treatment)
• Predicting OHSS risk
• Diagnosis of PCOS
• As a marker in granulosa cell tumor
• What are the normal values of the hormone AMH?
• Threshold value indicating that ovarian reserve is low:0.99
• Threshold value indicating OHSS risk:3,36

Average AMH levels were significantly higher in PCOS, low in POF and close to controls in hypothalamic amenorrhea.

There was a significant difference between normal, ovulatory and nonovulatory polycystic ovaries in terms of AMH production. (Ovulatory PCO is 4 times normal in granulosa cell cultures, 75 times normal in anovulatory PCO)

Prolactin Elevation (Hyperprolactinemia)

Prolactin is the hormone that provides milk production in the body. When the woman becomes pregnant, the rising hormones stimulate prolactin and produce milk from the breasts. In some women, early milk called colostrum can be secreted from the breasts without giving birth during the gestation period and this is considered normal.

The hormone prolactin is necessary for the development and function of the female reproductive organs at certain levels even without pregnancy. This hormone is produced by some cells in the organ called the pituitary in the lower part of our brain and released into the blood.

Again, it is kept under control by the release of another substance called Dopamine, which is secreted from the part of our brain called the hypothalamus.

What are the causes of Prolactin Elevation? (Hyperprolactinemia)

Prolactin hormone;

• In Pregnancy
• In tumors of the pituitary tissue, called adenomas,
• In Thyroid hormone disorders,
• In the elevation of estrogen hormone,
• In the case of reduced secretion of the hormone called dopamine (such as tumors, certain medications and destruction of the pituitary gland)
• In the use of some psychiatric or hypertension medications,
• In excessive chest (nipple) stimulation,
• It may increase, but sometimes no reason can be revealed.

The elevation of the hormone prolactin is called Hyperprolactinemia.

What happens in the body when the hormone prolactin rises (in the case of hyperprolactinemia)?

• Menstrual irregularities (low menstruation, infrequent menstruation, inability to menstruate)
• Nipple discharge (milk coming in outside pregnancy = galactorrhea)
• Inability to conceive (infertility) may occur due to disruption of ovulation
• The diagnosis of high prolactin is made by measuring the level of prolactin in the blood.

However, when making this measurement, some points should be considered:

• It should be checked between 10:00 and 11:00 in the morning,
• You should not have sexual intercourse on the morning of the test,
• Breast stimulation should be avoided for a few days before the test (tight bras should not be worn, breasts should not be rubbed even for washing),
• If possible, you should be hungry.
• The medications used, especially psychiatric drugs, should be discontinued.
• It is important to be away from stress before taking a blood sample, if possible, it is useful to rest in a quiet place for 10-15 minutes and take a blood sample.
• Women who apply with any one or more of the complaints of menstrual irregularity, inability to conceive, milk coming from the breasts outside the breastfeeding period are asked to measure the level of prolactin hormone in the blood.

When the hormone level in a woman diagnosed with hyperprolactinemia is above a certain level (usually normal is 5-25 ngr/ml), these areas are usually examined by a method that visualizes the hypothalamus and pituitary.

The aim of this examination is to determine whether the woman has a benign pituitary tumor called pituitary adenoma, which is the most common cause of hyperprolactinemia, and to investigate other rare conditions that may cause hyperprolactinemia in the region.

As an imaging method, a simple sella tursika (“cella turcica”) (anatomical region in the head where the pituitary is located) X-ray may be requested, or in cases where adenoma is suspected, CT (computed tomography) or MR (magnetic resonance) examinations, which are more sensitive but more costly, may be required.

Does high prolactin cause infertility?

One of the causes of infertility is the excessive rise of the hormone prolactin. However, infertility may not be seen in every person with high prolactin. As the prolactin hormone rises, deterioration in the ovulation function of the woman is observed. This deterioration is directly proportional to the level of the hormone prolactin. In other words, the higher the prolactin hormone, the more ovulation functions will be impaired and eventually no menstruation or even cessation of menstruation may occur.

While menstrual irregularity is often detected in women with high blood prolactin, there may or may not be complaints of milk coming from the breasts. It is not always possible for the breast tissue of a woman who is not in the gestation period to respond to the elevation of blood prolactin with the production of milk.

On the other hand, in women who complain of milk coming from their breasts, sometimes prolactin hormone measurements can be found normal. The likely reason for this is the presence of some sub-varieties of the hormone prolactin, which are not measured by today’s classical laboratory methods, but have strong milk-forming properties.

How is high prolactin level treated?

Hyperprolactinemia may respond well to medication treatment. The use of medication is the most valid and healthy method of treatment, hormone-directed medication that control the production and release of prolactin hormone into the blood are used, and the problem is eliminated with medication in most of the patients.

But medication is not an easy treatment because of the side effects. In some patients, it may cause problems such as dizziness, nausea and weakness, low blood pressure, which decrease over time and disappear when the treatment is over.

First of all, the reason that increases the level of Prolactin should be tried to be found and this cause should be treated. When the complaint is the inability to conceive and the person has a high level of prolactin, medications that reduce the level of prolactin and sometimes medications that provide ovulation are used.

When the problem is milk coming from the breasts, medications that reduce the level of prolactin are used. When the complaint is menstrual irregularity, medications that reduce prolactin levels can be used, but in a woman who does not want to have children, medications such as birth control pills that only eliminate the symptom, that is, regulate menstrual bleeding, can be used.

How is the Treatment of Pituitary Adenoma?

When benign tumors called pituitary adenoma are detected in the person with imaging methods, it is first investigated whether this creates pressure symptoms.

Adenomas are benign tumors and are quite common, do not tend to become cancerous, and usually grow slowly. In the autopsies performed, pituitary adenoma can be found in 5% of women who are 70 years old and known to have no complaints.

Although those with pituitary adenomas smaller than one centimeter in diameter are called microadenomas and large ones are called macroadenomas, what is important is not the size of the adenoma but whether it presses on the surrounding tissues, growth and hormone secretion rate.

Although the degree of pressure exerted by pituitary adenoma on the environment is usually clearly observed in the imaging method, visual field examination is also used to investigate the presence of pressure on the visual nerve.

Most adenomas can be treated with prolactin-lowering medications. Thus, operations are very rarely preferred. Surgery may be required especially for adenomas that cause severe symptoms (severe headache, very narrowed visual field) or tend to grow rapidly.

Today’s view; If the woman has no complaints and is incidentally detected with hyperprolactinemia, it is not very important. It is now known that prolactin has different types of molecules and that the elevations of prolactin, which do not cause clinical complaints, are largely dependent on inactive molecules and do not need to be treated.

What are Tests to Assess Thyroid Gland Function?

• Free T4 (fT4)
• Total T4 (T4)
• Total T3 (T3)
• TSH

Today, laboratory methods have been developed that can show even very low levels of TSH in the blood.

Among these tests, fT4 is the best reflection of blood hormone levels and is usually preferred in combination with TSH measurement. Blood TSH measurement is a sensitive method that can reflect thyroid gland functions even by itself, and high levels in the blood indicate that thyroid gland hormones (T3, T4) are low, and low thyroid gland hormones are high. In such cases, the fT4 level is evaluated and the degree of low or high is determined.

Although in some cases TSH levels are outside normal ranges, thyroid gland hormone levels can be found within normal limits. This situation indicates that the pituitary gland is trying to compensate for the event by being overly active (by producing more TSH) or vice versa (by producing less TSH) and making it possible to detect the disease before it starts to show symptoms.

Do thyroid hormone disorders affect pregnancy?

In addition to TSH hormone secretion, TRH also manages the secretion of Prolactin hormone from the pituitary. For this reason, conditions that cause an increase in TRH hormone (hypothyroidism, ie thyroid hormone secretion insufficiencies) can also cause an increase in prolactin hormone. In any case where prolactin hormone secretion disorder is suspected, the TSH level is also examined in addition to the blood prolactin hormone level (TSH will increase as TRH increases, so the TSH level, which is easier to measure, is checked at instead of TRH).

Although there are no exact data on this subject in Turkey, the average age of menopause of women in the U.S. has been determined as 50.7 years. 1-2% of women enter menopause after the age of 60 and 1-2% before the age of 40. Entering menopause before the age of forty is called early menopause or premature ovarian insufficiency. The most important factor determining the age of menopause is genetic factors. In addition, environmental factors such as smoking can affect the age of menopause.

What is premature ovarian failure?

It is determined according to the number of germ cells in the life span of the ovaries. In the 20th week of pregnancy, there are 3.5 million eggs in each ovary, while this number decreases to 1 million in each ovary at birth, 300,000 during adolescence and 10,000 at age 40. During reproductive age, only about 500 eggs become mature and potentially capable of resulting in pregnancy. After the age of forty, an acceleration in the loss of eggs is observed.

The diagnosis of menopause is made by the levels of FSH, LH and E2 hormones in the blood. In occult ovarian insufficiency, which is defined as “Occult ovarian insufficiency”, although the patient has normal menstruation, the blood FSH level is 2 standard deviations above the average determined for that age group and ultrasound shows a decrease in the number of structures called follicles in the ovary, which indicate the egg production reserve. This is one of the important reasons for not being able to have children in patients who cannot become pregnant even though there is no reason.

What are the Causes of Premature Ovarian Failure?

Genetic Causes: Genetic causes are seen in 40% of patients with premature ovarian failure. Studies have shown that 5-30% of premature ovarian failure is familial. The genetic mode of transmission can be X-linked, automosomal dominant or recessive. However, no exact data has been revealed about how genetic transmission occurs. In these families, no disorder is seen in male individuals.

Turner Syndrome: This syndrome occurs as a result of the fact that the chromosome structure is XO, that is, the sex chromosome, which should be two, is single. Although a very small number of these patients can enter the puberty period, in general, these patients do not have any menstruation and sexual development.

Minor disorders in the X-chromosome: While the absence of an X chromosome at all causes Turner syndrome, partial losses in the long arm of the chromosome may only cause ovarian disorders in the patient and the patient may not menstruate at all or may enter early menopause. Again, the presence of disorders called translocation in the X chromosome can cause early menopause. Early menopause can also be seen in a chromosome disorder called X mosaicism. Finally, early menopause can be seen in girls in the chromosome disorder called Fragile-X syndrome, which is usually accompanied by severe retardation in the boys of the family.

Enzyme Deficiencies:

• I. 17-Hydroxylase
• II. Steroidogenic acute regulatory protein
• III. Aromatase
• IV. Galactose-1-phosphate uridyl transferase

Genetic Mutations in the Follicle Stimulating Hormone Receptor: In case of complete loss of receptors affected by FSH hormone, the patient does not menstruate at all, while early menopause is seen in partial losses.

Perrault Syndrome: It is an autosomal recessive genetic disease; It is characterized by congenital deafness, short stature and lack of development of the ovaries.
Ataxia-telangiectasia: In this disease, which is characterized by impaired cerebellum function, susceptibility to cancer, immune system deficiency and sensitivity to radiation, developmental disorders can also be seen in the ovaries. The disease is inherited as an autosomal recessive.

Inhibin gene disorders

Infections of the Ovaries Due to Viruses:

In 2-8% of women who have had mumps infection, infection is also seen in the ovaries. It is suggested that this infection can cause ovarian destruction, leading to early menopause. In addition, although it has been suggested that there is a relationship between cytomegalovirus, malaria, chickenpox and dysentery and early menopause, definitive evidence has not been established in this opinion.

Chemotherapy and Radiotherapy

Disorders of the Immune System:

In a small proportion of patients with premature ovarian insufficiency, antibodies to the ovaries are synthesized, leading to the destruction of ovarian tissue. In this group of patients, the likelihood of diseases characterized by the production of antibodies against the patient’s own tissues increases. This group of diseases called autoimmune diseases can occur as thyroid, parathyroid and adrenal gland disorders, some rheumatic diseases, some blood diseases and diabetes.

How is Premature Ovarian Failure diagnosed?

The diagnosis of premature ovarian failure is made by looking at the levels of FSH, LH and E2 hormones in the blood. For a definitive diagnosis, blood samples should be examined 1 week apart and 4 times. Taking into account the increased risk of autoimmune disease in some of these patients after diagnosis, the following tests should be performed:

Calcium, phosphorus, fasting blood glucose, fasting cortisol level, free thyroid hormones, TSH, thyroid antibodies, blood count, sedimentation rate, total protein/globulin, rheumatoid factor, ANA

In addition, if the patient is under 30 years of age, chromosome analysis should be performed.

How is the treatment of Premature Ovarian Insufficiency?

There is nothing that can be done except hormone supplementation in patients who are due to chromosome disorders and who have never menstruated. The only way to have children in these patients is egg donation. Again, due to chromosome disorders, but in cases where the patient enters menopause after puberty, there is nothing that can be done except hormone replacement and egg donation if a child is desired.

First of all, it is necessary to consider that 10-20% of these patients may have a spontaneous return and therefore it is necessary to look at the hormone values at regular intervals. If the patient wants to have a child, FSH and LH levels in the blood should be examined, and if the FSH / LH ratio is less than 1, ovarian stimulating medications should be given. Although there is nothing definite about the treatment to be applied in this period (IVF, insemination….), IVF seems to be more logical. In other patients, hormone therapy should be started to prevent osteoporosis and other menopausal symptoms. It should be remembered that during hormone therapy, 10-20% of patients can spontaneously come out of menopause and therefore patients can become pregnant. Hormone therapy does not prevent pregnancy and there is no serious anomaly potential on the pregnancy that occurs.

Apart from these, the most important way to have children is egg donation.

In “occult-hidden ovarian failure”, that is, in cases where the FSH hormone is high even though the patient has normal menstruation, IVF should be tried first. In these patients, medication may not be used for IVF, that is, IVF can be performed in natural cycle. Although few eggs are obtained in the young patient group, significant success can be achieved. The patient should also be told that this group of patients will enter menopause early

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