Month: December 2021

Clomiphene: Characteristics of the substance

Characteristic of the substance Clomiphene is a white or white crystalline powder with a cream tint. Slightly soluble in water, moderately soluble in alcohol.

Pharmacological action is antiestrogenic. Binds estrogen receptors in the hypothalamus and ovaries. When ingested, it is well absorbed from the gastrointestinal tract. It is metabolized in the liver. It is excreted with bile, undergoes enterohepatic recirculation. It is excreted from the body with feces. T1/2 is 5-7 days. In small doses, it enhances the secretion of gonadotropins, stimulates ovulation. With a low content of endogenous estrogens in the body, it has a moderate estrogenic effect, with a high level — antiestrogenic. By reducing the level of circulating estrogens, it promotes the secretion of gonadotropins. In large doses, it inhibits the secretion of gonadotropins. It does not have gestagenic and androgenic activity.

Application of the substance Clomiphene

Anovulatory infertility (ovulation induction), dysfunctional uterine bleeding, amenorrhea (dysgonadotropic form, secondary, postcontractive), galactorrhea (against the background of pituitary tumor), polycystic ovaries (Stein—Leventhal syndrome), Chiari-Frommel syndrome, androgen deficiency, oligospermia, for the diagnosis of disorders of the gonadotropic function of the pituitary gland.

Anovulatory infertility (ovulation induction); amenorrhea (dysgonadotropic form), secondary amenorrhea, post-contraceptive amenorrhea; Stein-Leventhal syndrome (polycystic ovary syndrome); oligomenorrhea; galactorrhea (on the background of a pituitary tumor); Chiari-Frommel syndrome (syndrome of prolonged postpartum amenorrhea-galactorrhea); androgen deficiency; in men – oligospermia.

clomiphene

Contraindications

Hypersensitivity, severe hepatic and/or renal insufficiency, uterine bleeding of unknown etiology, ovarian cyst, tumor or insufficiency of pituitary function, pregnancy (including suspicion of it).

Hypersensitivity to clomiphene; pregnancy, lactation (breastfeeding); ovarian cyst (with the exception of polycystic ovarian syndrome); tumor or hypofunction of the pituitary gland; thyroid or adrenal dysfunction; metrorrhagia of unclear etiology; long-term or recently developed visual disturbances; neoplasms of the genitals; endometriosis; ovarian insufficiency against hyperprolactinemia.

Special instructions

It is recommended to check liver function before using clomiphene.

Before using Clomid, it is necessary to conduct a thorough gynecological examination. The use of clomiphene is indicated in cases when the total level of gonadotropin in the urine is below the lower limit of the norm or at the normal level, ovarian palpation does not reveal deviations from the norm, and the functions of the thyroid gland and adrenal glands correspond to the norm.

In the absence of egg maturation, all other possible causes of infertility should be excluded or treated before the use of clomiphene. If an increase in the ovaries or their cystic transformation is detected, the use of clomiphene is not allowed until the ovaries return to normal size. In the future, the dose or duration of treatment should be reduced.

In the course of treatment, constant supervision of a gynecologist is necessary, ovarian function should be monitored, vaginal examinations should be performed, and the phenomenon of the “pupil” should be observed. Often during the course of treatment it is difficult to determine the moment of ovulation, and there is also often a deficiency of the corpus luteum. Therefore, after conception, it is recommended to start preventive administration of progesterone.

Effectiveness of clomid

Effectiveness of clomid: Arrighi’s data on the low efficacy of clomiphene in patients with an inferior luteal phase confirm the good results we have obtained in the treatment of this pathology with synthetic progestins. So, according to Townsend, clomiphene will give effect only with a daily excretion of estrogens of at least 10 mcg /day. According to other authors, ovulation stimulation with clomiphene is possible only in patients with estrogen excretion of at least 20 mcg per day.

There are indications of low efficacy of clomiphene in patients with initial high gonadotropin secretion. Obviously, this applies to patients whose ovarian tissue is unable to respond to stimulation with gonadotropins and clomiphene.

A summary analysis of the data on the use of clomiphene in 6714 patients with anovulation, conducted by Macgregor, showed that ovulation appears in 70%, and pregnancy occurs only in 32.7% of women. Such a discrepancy between the frequency of ovulation and the onset of pregnancy is usually explained by the appearance of cyclic secretion of LH at an inappropriate time, resulting in premature luteinization of follicles without full ovulation.

Purpose and effectiveness of clomid

The administration of clomiphene in patients with impaired gonadotropin secretion revealed its low effectiveness compared to gonadotropins. In addition, it should be noted that every 5th woman with the onset of pregnancy after the use of clomiphene has an interruption in the second trimester (18.5%).

Our own experience of using clomiphene in 51 patients (in the presence of anovulation in 22 and an incomplete luteal phase in 29) showed that ovulation occurred in almost all women, and pregnancy occurred only in 18 of 51, i.e. in every third patient.

effectiveness of clomid

Effect

At the same time, the best effect was achieved in patients with anovulation. Ovulation was confirmed by an increase in the excretion of total estrogens by 2-3 times, and pregnanediol by 3 times. In most patients, 10-12 days after the end of taking clomiphene, the excretion of estrogens increases to 50-70 mcg / day and ovulation occurs, followed by an increase in basal temperature and the excretion of pregnanediol. If pregnancy has not occurred, then a menstrual-like reaction occurs 10-12 days after the basal temperature rises.

The effectiveness of clomid (treatment with clomiphene) in patients with estrogen excretion below 10 mcg / day was insignificant. Only 1 out of 8 patients with prolonged amenorrhea became pregnant. The relatively low effectiveness of treatment with clomiphene in patients with an inferior luteal phase was also noted.

Blood and testosterone

So, blood and testosterone. The red bone marrow is the most important organ of the hematopoietic system in humans, which carries out hematopoiesis, or hematopoiesis — the process of creating new blood cells to replace dying and dying ones.

Hematopoiesis is the blood production that occurs in the bone marrow, due to stimulation by erythropoietin.

Erythropoietin is a hormone synthesized in the kidneys. It stimulates the formation of red blood cells in the bone marrow.

Erythrocytes are blood cells containing hemoglobin. Their main function is to deliver oxygen to tissues and organs.

Hemoglobin is a protein contained in red blood cells and carries out the exchange of oxygen between the lungs and tissues of the body.

Hematocrit is defined as the ratio of the total volume of all shaped elements to the total volume of blood.

Platelets are blood cells in the form of blood plates, whose main function is to participate in blood clotting. They are formed in the bone marrow and protect the body from bleeding, as well as react to vascular damage by forming blood clots.

Steroids and blood

Blood and testosteroneЖ When it comes to the side effects associated with the use of testosterone, the term “Thick blood” often arises, this term is not particularly scientific and does not mean what it really is.

Blood and testosterone

In fact, the so-called thick blood is an increase in the amount of hemoglobin and red blood cells, which in turn leads to an increase in hematocrit. It is the increase in hematocrit that is the increase in blood density, which is due to the intake of testosterone. Since testosterone increases the secretion of erythropoietin, which significantly stimulates hematopoiesis.This is a normal situation when taking testosterone, so you should not always worry if hematocrit grows. The main thing is that the hematocrit remains within the reference values, norms.

Blood and testosterone: Norms

Hematocrit – 39-51%

Hemoglobin – 130-170 g/l

Erythrocytes – 4.2-5.7 million/ml

Platelets — 180-350 thousand/ml

In turn, increased hematocrit will lead to certain side effects. In fact, there are two of them. The first is an increase in the load on the cardiovascular system, because of the thicker blood, the movement of blood through the vessels is hampered, which leads to an increased load on the heart and blood vessels. This usually manifests itself in the form of increased blood pressure and heart rate. The second is the risk of blood clot formation, the risk of thrombosis. This is due to an increase in the number of red blood cells.

Prerequisites for an increase in hematocrit

  1. Smoking
  2. Insufficient water consumption

An increase in hematocrit, erythrocytes and hemoglobin is called Erythrocytosis. Erythrocytosis is of two types, primary and secondary. Primary erythrocytosis – occurs as a result of true polycythemia, a myeloproliferative neoplasm in which pathological cells in the bone marrow produce too many red blood cells. Secondary erythrocytosis develops as a result of a disease in which the secretion of erythropoietin increases. Erythropoietin is a hormone that is synthesized in the kidneys and stimulates the production of red blood cells by the bone marrow.

Blood and testosterone: Elevated platelets

Risk of thrombosis. An increase in platelets is called thrombocytosis. There are two types of thrombocytosis: Primary and secondary. Primary thrombocytosis, in this case, an increased number of megakaryocytes is formed in the bone marrow, which increases the number of platelets having a normal lifespan, but an incorrect structure and impaired functions. Secondary (reactive) thrombocytosis. With it, platelets function normally, and the cause of the disease itself is some other deviation.

Take even clomid very carefully. When taking pharmacology, secondary thrombocytosis develops. It passes after the withdrawal of drugs.

Methods of reducing hematocrit

Phlebotomy

Phlebotomy is bloodletting. The procedure is resorted to in the case of polycythemia, a hematological disease in which too many red blood cells, leukocytes, platelets are produced in bone marrow cells, which can lead to thrombosis.

Erythrocytapheresis

Erythrocytapheresis is a method of extracorporeal hemocorrection based on the removal of certain cellular components of the patient’s blood – erythrocytes. The indications for it correspond to the indications for ordinary bloodletting.

Blood and testosterone: Conclusions

Using chemotherapy drugs to reduce hematocrit, while increasing the risk of developing leukemia, instead of doing erythrocytopheresis or phlebotomy, which are very safe, does not seem to be a very good idea.

In general, discussing the number of side effects and the effectiveness of interferon alpha, hydroxyurea or pipobrovan, which, by the way, is more preferable than hydroxyurea, would make sense if not for one thing — erythrocytapheresis or phlebotomy have no side effects at all and they are more effective.

From the author: My guess is that in general someone thought of using these drugs instead of draining blood just because he was too lazy to go and drain the blood, since it’s obviously easier to take a pill. I’m still in shock that someone is seriously considering taking such drugs. Yes, hematocrit 54% will be safer than taking hydroxyurea. It will be safer to do nothing here than to do something.

Clomiphene therapy is over, and testosterone is holding up.

Clomiphene therapy is used primarily as a supportive therapy for secondary hypogonadotropic hypogonadism or testosterone deficiency. With hypogonadotropic testosterone deficiency, LH, the pituitary hormone that stimulates the testicles to release testosterone, decreases. The reason for the decrease in LH, most often, it is impossible to determine. The main, and most frequent, reason is age. With age, LH decreases significantly, which leads to a deficiency of testosterone.

Clomiphene therapy

The main goal of clomiphene therapy is to maintain LH at higher values. It should be understood that clomiphene therapy is not curative, it will not “cure” the testicles or pituitary gland, so that later more hormones are released for a long time than before the start of therapy. Clomiphene increases LH only for as long as it works. As soon as clomiphene is canceled, the LH level begins to decrease to the same values that were before the start of therapy.

clomiphene therapy

On the graph, you can see how testosterone behaves on maintenance therapy for a year, from 1 to 13 tests, which were once a month. 14 the delivery of tests was 4 months after the cancellation of clomiphene. In this analysis, the level of testsoteron returned to the same values that were before the start of therapy.

From this graph, it can be seen that the testosterone level was good only while taking clomiphene, and there is no effect of testosterone retention after discontinuation of medications in maintenance therapy.

Interesting notes on therapy

  1. Testosterone in good values, more than 20+ nmol/L, does not come out very quickly. Initially, the man had a very low testosterone of 9 nmol/ l, after a month it rose only to 14.6 mmol / L. After 2-3 months it was at the level of 20 nmol/ l and only after 5-6 months it reached 30 nmol/l.
  2. There may be fluctuations in testosterone levels on the therapy itself. Here is an example of the fact that throughout the year testosterone fluctuated between 20-30 nmol/L. This happens if testosterone has dropped from 30 nmol/l to 20 nmol/l, this does not mean that therapy does not work, it’s time to finish and only HRT remains. Such fluctuations can be – this is normal. The main thing is to compare testosterone not only with the previous analysis or analysis at the highest point, but also with the initial analysis. Even if testosterone drops from 30 nmol/l to 20 nmol/l, it is still 2 times more than the original 9 nmol/l.
  3. After maintenance therapy, testosterone does not hold at all. Clomiphene therapy is initially a stimulating, supportive therapy. It increases the level of LH, which is low for one reason or another, which increases and keeps the testosterone level in good values. After the withdrawal of clomiphene, essentially what stimulates the level of LH, testosterone levels are reduced to the initial tests. In this case, the analysis with 30 nmol/l was in early March. Then the coronavirus and self-isolation, the cancellation of medications and tests in early July, the testosterone level is the same as the original one, which was almost 2 years ago.

Contraindications to ovulation stimulation

Ovulation stimulation

Ovulation stimulation is a technique of influencing the work of the ovaries, which is carried out within the framework of in vitro fertilization programs or situations when there is no ovulation of one’s own. The procedure allows you to eliminate one of the common causes of female infertility – the inability of the ovaries to form a mature egg and, thus, maximize the chance of pregnancy. Are there any contraindications to ovulation stimulation?

What is ovulation stimulation?

The essence of stimulation is the appointment of hormonal drugs that increase the level of hormones necessary for ovulation and, thereby, ensure the growth of follicles in the ovaries to the state of mature, preovulatory.

The drugs are administered strictly according to the scheme drawn up by a reproductive doctor, taking into account the age, health status and reproductive system of a woman.

The procedure allows you to get more eggs ready for fertilization and is successfully used both in assisted reproductive technology programs.

Ovulation stimulation and pregnancy

The complete or partial absence of natural ovulation is one of the most common causes of female infertility. In this case, an additional push with the help of hormonal drugs allows you to achieve pregnancy naturally without the use of IVF and other reproductive technologies.

Ovulation stimulation for conception is carried out under the condition of complete patency of the fallopian tubes and good sperm counts in the partner. The first attempts are carried out using tablet preparations. As the egg matures and exits, the doctor informs the patient of the most favorable days for conception. The protocol ensures the maturation and release of one, rarely two eggs, as it happens with a natural cycle.

If pregnancy does not occur within 6 months of attempts, reproductologists prescribe injectable drugs. Their use significantly increases the likelihood of pregnancy in general and multiple pregnancies, in particular, since it often promotes the growth of several germ cells.

Contraindications to ovulation stimulation

If there are no other obstacles to pregnancy, doctors recommend using ovulation stimulation, since the price of the procedure is significantly lower than the cost of other reproductive technologies.

Contraindications to ovulation stimulation

Hormones used to stimulate ovulation significantly change the work of the body, which is why doctors pay special attention to the state of a woman’s health. Contraindications to ovulation stimulation in the presence of the following problems:

  • the patency of the fallopian tubes is disrupted or not investigated (if it is planned to stimulate the ovaries for pregnancy naturally);
  • when the follicular reserve is depleted (determined by the level of follicle-stimulating hormone);
  • the duration of infertility treatment is 2 years or more;
  • there are diseases of internal organs or mental abnormalities that are a contraindication for pregnancy;
  • tumors of the uterus or ovaries were detected;
  • the ovaries are enlarged or contain cysts in their structure;
  • there are signs of inflammation (regardless of its location);
  • the woman suffers from uterine bleeding of unknown origin;
  • the functioning of the liver or kidneys is significantly impaired;
  • there are disorders of the endocrine glands that cannot be corrected;
  • the woman does not tolerate any component of the drug;
  • a woman is 40 years old or older.