Hyperprolactinemia and Infertility

1. Hyperprolactinemia and Infertility Presented by: Khuzama alkayid Rawan Almohammady

2. Objectives 1- To discuss the physiology of prolactin. 2- To define infertility. 3- To list the causes of infertility. 4- To discuss the pathophysiology of hyperprolactinemia and its relation to infertility . 5- To discuss the management of hyperprolactinemia.

3. The physiology of prolactin Prolactin is a single-chain protein hormone closely related to growth hormone. It is secreted by the lactotrophs in the anterior pituitary. The normal values for prolactin are as follows: Males: 2 - 18 ng/mL Non-pregnant females: 2 - 29 ng/mL Pregnant women: 10 - 209 ng/mL

4. Physiology of Prolactin Dopamine serves as the major prolactin-inhibiting factor on prolactin secretion. Dopamine is secreted into portal blood by hypothalamic neurons, binds to receptors on lactotrophs, and inhibits both the synthesis and secretion of prolactin. Agents and drugs that interfere with dopamine secretion or receptor binding lead to enhanced secretion of prolactin. In addition to tonic inhibition by dopamine, prolactin secretion is positively regulated by several hormones, including thyroid-releasing hormone, gonadotropin-releasing hormone and vasoactive intestinal polypeptide. Stimulation of the nipples and mammary gland, as occurs during nursing, leads to prolactin release. This effect appears to be due to a spinal reflex arc that causes release of prolactin-stimulating hormones from the hypothalamus. Estrogens provide a positive control over prolactin synthesis and secretion.

5. Physiology of Prolactin -Prolactin induces lobuloalveolar growth of the mammary gland. Alveoli are the clusters of cells in the mammary gland that actually secrete milk. -Prolactin stimulates lactogenesis or milk production after giving birth. Prolactin, along with cortisol and insulin, act together to stimulate transcription of the genes that encode milk proteins.

6. Physiology of Prolactin

7. 2- To define infertility Infertility is the biological inability of a person to contribute to conception.

8. 3- To list the causes of infertility.

9. Causes of male infertility 1-Impaired production or function of sperm: Impaired shape and movement of sperm. Low sperm concentration. Varicocele. Undescended testicle. Testosterone deficiency (male hypogonadism). Infections. Impaired shape and movement of sperm. Sperm must be properly shaped and able to move rapidly and accurately toward the egg for fertilization to occur. If the shape and structure (morphology) of the sperm are abnormal or the movement (motility) is impaired, sperm may not be able to reach or penetrate the egg. Low sperm concentration. A normal sperm concentration is greater than or equal to 20 million sperm per milliliter of semen. A count of 10 million or fewer sperm per milliliter of semen indicates low sperm concentration (subfertility). A count of 40 million sperm or higher per milliliter of semen indicates increased fertility. Complete failure of the testicles to produce sperm is rare. Varicocele. A varicocele is a varicose vein in the scrotum that may prevent normal cooling of the testicle, leading to reduced sperm count and motility. Undescended testicle. Undescended testicle occurs when one or both testicles fail to descend from the abdomen into the scrotum during fetal development. Because the testicles are exposed to the higher internal body temperature, compared with the temperature in the scrotum, sperm production may be affected. Testosterone deficiency (male hypogonadism). Infertility can result from disorders of the testicles themselves or from an abnormality affecting the hypothalamus or pituitary gland in the brain that produces the hormones that control the testicles. Genetic defects. In the genetic defect Klinefelter's syndrome, a man has two X chromosomes and one Y chromosome instead of one X and one Y. This causes abnormal development of the testicles, resulting in low or absent sperm production and possibly low testosterone. Infections. Infection may temporarily affect sperm motility. Repeated bouts of sexually transmitted diseases (STDs), such as chlamydia and gonorrhea, are most often associated with male infertility. These infections can cause scarring and block sperm passage. If mumps, a viral infection usually affecting young children, occurs after puberty, inflammation of the testicles can impair sperm production. Inflammation of the prostate (prostatitis), urethra or epididymis also may alter sperm motility. In many instances, no cause for reduced sperm production is found. When sperm concentration is less than 5 million per milliliter of semen, genetic causes could be involved. Genetic testing can reveal whether there are subtle changes in the Y chromosome. Impaired shape and movement of sperm. Sperm must be properly shaped and able to move rapidly and accurately toward the egg for fertilization to occur. If the shape and structure (morphology) of the sperm are abnormal or the movement (motility) is impaired, sperm may not be able to reach or penetrate the egg. Low sperm concentration. A normal sperm concentration is greater than or equal to 20 million sperm per milliliter of semen. A count of 10 million or fewer sperm per milliliter of semen indicates low sperm concentration (subfertility). A count of 40 million sperm or higher per milliliter of semen indicates increased fertility. Complete failure of the testicles to produce sperm is rare. Varicocele. A varicocele is a varicose vein in the scrotum that may prevent normal cooling of the testicle, leading to reduced sperm count and motility. Undescended testicle. Undescended testicle occurs when one or both testicles fail to descend from the abdomen into the scrotum during fetal development. Because the testicles are exposed to the higher internal body temperature, compared with the temperature in the scrotum, sperm production may be affected. Testosterone deficiency (male hypogonadism). Infertility can result from disorders of the testicles themselves or from an abnormality affecting the hypothalamus or pituitary gland in the brain that produces the hormones that control the testicles. Genetic defects. In the genetic defect Klinefelter's syndrome, a man has two X chromosomes and one Y chromosome instead of one X and one Y. This causes abnormal development of the testicles, resulting in low or absent sperm production and possibly low testosterone. Infections. Infection may temporarily affect sperm motility. Repeated bouts of sexually transmitted diseases (STDs), such as chlamydia and gonorrhea, are most often associated with male infertility. These infections can cause scarring and block sperm passage. If mumps, a viral infection usually affecting young children, occurs after puberty, inflammation of the testicles can impair sperm production. Inflammation of the prostate (prostatitis), urethra or epididymis also may alter sperm motility. In many instances, no cause for reduced sperm production is found. When sperm concentration is less than 5 million per milliliter of semen, genetic causes could be involved. Genetic testing can reveal whether there are subtle changes in the Y chromosome.

10. 2-Impaired delivery of sperm: Retrograde ejaculation. Blockage of epididymis or ejaculatory ducts. No semen (ejaculate). Misplaced urinary opening (hypospadias). Impaired delivery of sperm. Problems with the delivery of sperm from the penis into the vagina can result in infertility. These may include: Retrograde ejaculation. This occurs when semen enters the bladder during orgasm rather than emerging out through the penis. Various conditions can cause retrograde ejaculation, including diabetes, bladder, prostate or urethral surgery, and the use of certain medications. Blockage of epididymis or ejaculatory ducts. Some men are born with blockage of the part of the testicle that contains sperm (epididymis) or ejaculatory ducts. Some men lack the tube that carries sperm (vas deferens) from the testicle out to the opening in the penis. No semen (ejaculate). The absence of ejaculate may occur in men with spinal cord injuries or diseases. This fluid carries the sperm from the penis into the vagina. Misplaced urinary opening (hypospadias). A birth defect can cause the urinary (urethral) opening to be abnormally located on the underside of the penis. If not surgically corrected, this condition can prevent sperm from reaching the woman's cervix. Anti-sperm antibodies. Antibodies that target sperm and weaken or disable them usually occur after surgical blockage of part of the vas deferens for male sterilization (vasectomy). Presence of these antibodies may complicate the reversal of a vasectomy. Impaired delivery of sperm. Problems with the delivery of sperm from the penis into the vagina can result in infertility. These may include: Retrograde ejaculation. This occurs when semen enters the bladder during orgasm rather than emerging out through the penis. Various conditions can cause retrograde ejaculation, including diabetes, bladder, prostate or urethral surgery, and the use of certain medications. Blockage of epididymis or ejaculatory ducts. Some men are born with blockage of the part of the testicle that contains sperm (epididymis) or ejaculatory ducts. Some men lack the tube that carries sperm (vas deferens) from the testicle out to the opening in the penis. No semen (ejaculate). The absence of ejaculate may occur in men with spinal cord injuries or diseases. This fluid carries the sperm from the penis into the vagina. Misplaced urinary opening (hypospadias). A birth defect can cause the urinary (urethral) opening to be abnormally located on the underside of the penis. If not surgically corrected, this condition can prevent sperm from reaching the woman's cervix. Anti-sperm antibodies. Antibodies that target sperm and weaken or disable them usually occur after surgical blockage of part of the vas deferens for male sterilization (vasectomy). Presence of these antibodies may complicate the reversal of a vasectomy.

11. 3-General health and lifestyle: Emotional stress. Malnutrition. Obesity. Cancer and its treatment. Age. General health and lifestyle. A man's general health and lifestyle may affect fertility. Some common causes of infertility related to health and lifestyle include: Emotional stress. Stress may interfere with certain hormones needed to produce sperm. Your sperm count may be affected if you experience excessive or prolonged emotional stress. A problem with fertility itself can sometimes become long term and discouraging, producing more stress. Malnutrition. Deficiencies in nutrients such as vitamin C, selenium, zinc and folate may contribute to infertility. Obesity. Increased body mass may be associated with fertility problems in men. Cancer and its treatment. Both radiation and chemotherapy treatment for cancer can impair sperm production, sometimes severely. The closer radiation treatment is to the testicles, the higher the risk of infertility. Removal of one or both testicles due to cancer also may affect male fertility. Age. Men older than age 40 may be less fertile than younger men. General health and lifestyle. A man's general health and lifestyle may affect fertility. Some common causes of infertility related to health and lifestyle include: Emotional stress. Stress may interfere with certain hormones needed to produce sperm. Your sperm count may be affected if you experience excessive or prolonged emotional stress. A problem with fertility itself can sometimes become long term and discouraging, producing more stress. Malnutrition. Deficiencies in nutrients such as vitamin C, selenium, zinc and folate may contribute to infertility. Obesity. Increased body mass may be associated with fertility problems in men. Cancer and its treatment. Both radiation and chemotherapy treatment for cancer can impair sperm production, sometimes severely. The closer radiation treatment is to the testicles, the higher the risk of infertility. Removal of one or both testicles due to cancer also may affect male fertility. Age. Men older than age 40 may be less fertile than younger men.

12. Causes of female infertility Fallopian tube damage or blockage. Endometriosis. Ovulation disorders. hyperprolactinemia. Polycystic ovary syndrome (PCOS). Uterine fibroids. Thyroid problems. Causes of female infertilityThe most common causes of female infertility include fallopian tube damage or blockage, endometriosis, ovulation disorders, elevated prolactin, polycystic ovary syndrome (PCOS), early menopause, benign uterine fibroids and pelvic adhesions. Fallopian tube damage or blockage. Fallopian tube damage usually results from inflammation of the fallopian tube (salpingitis). Chlamydia, a sexually transmitted disease, is the most frequent cause. Tubal inflammation may go unnoticed or may cause pain and fever. Tubal damage may result in a pregnancy in which the fertilized egg is unable to make its way through the fallopian tube to implant in the uterus (ectopic pregnancy). One episode of tubal infection may cause fertility difficulties. The risk of ectopic pregnancy increases with each occurrence of tubal infection. Endometriosis. Endometriosis occurs when the uterine tissue implants and grows outside of the uterus — often affecting the function of the ovaries, uterus and fallopian tubes. These implants respond to the hormonal cycle and grow, shed and bleed in sync with the lining of the uterus each month, which can lead to scarring and inflammation. Pelvic pain and infertility are common in women with endometriosis. Ovulation disorders. Some cases of female infertility are caused by ovulation disorders. Disruption in the part of the brain that regulates ovulation can cause low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Even slight irregularities in the hormone system can prevent the ovaries from releasing eggs (anovulation). Specific causes of hypothalamic-pituitary disorders that can result in anovulation include injury, tumors, excessive exercise and starvation. In addition, some medications can be associated with ovulation disorders. Elevated prolactin (hyperprolactinemia). The hormone prolactin stimulates breast milk production. High levels in women who aren't pregnant or nursing may affect ovulation. An elevation in prolactin levels may also indicate the presence of a pituitary tumor. In addition, some drugs can elevate levels of prolactin. Milk flow not related to pregnancy or nursing can be a sign of high prolactin. Polycystic ovary syndrome (PCOS). In PCOS, your body produces too much androgen hormone, which affects ovulation. PCOS is also associated with insulin resistance and obesity. Uterine fibroids. Fibroids are benign tumors in the wall of the uterus and are common in women in their 30s and 40s. Rarely, they may cause infertility by blocking the fallopian tubes. More often, fibroids interfere with proper implantation of the fertilized egg. Causes of female infertilityThe most common causes of female infertility include fallopian tube damage or blockage, endometriosis, ovulation disorders, elevated prolactin, polycystic ovary syndrome (PCOS), early menopause, benign uterine fibroids and pelvic adhesions. Fallopian tube damage or blockage. Fallopian tube damage usually results from inflammation of the fallopian tube (salpingitis). Chlamydia, a sexually transmitted disease, is the most frequent cause. Tubal inflammation may go unnoticed or may cause pain and fever. Tubal damage may result in a pregnancy in which the fertilized egg is unable to make its way through the fallopian tube to implant in the uterus (ectopic pregnancy). One episode of tubal infection may cause fertility difficulties. The risk of ectopic pregnancy increases with each occurrence of tubal infection. Endometriosis. Endometriosis occurs when the uterine tissue implants and grows outside of the uterus — often affecting the function of the ovaries, uterus and fallopian tubes. These implants respond to the hormonal cycle and grow, shed and bleed in sync with the lining of the uterus each month, which can lead to scarring and inflammation. Pelvic pain and infertility are common in women with endometriosis. Ovulation disorders. Some cases of female infertility are caused by ovulation disorders. Disruption in the part of the brain that regulates ovulation can cause low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Even slight irregularities in the hormone system can prevent the ovaries from releasing eggs (anovulation). Specific causes of hypothalamic-pituitary disorders that can result in anovulation include injury, tumors, excessive exercise and starvation. In addition, some medications can be associated with ovulation disorders. Elevated prolactin (hyperprolactinemia). The hormone prolactin stimulates breast milk production. High levels in women who aren't pregnant or nursing may affect ovulation. An elevation in prolactin levels may also indicate the presence of a pituitary tumor. In addition, some drugs can elevate levels of prolactin. Milk flow not related to pregnancy or nursing can be a sign of high prolactin. Polycystic ovary syndrome (PCOS). In PCOS, your body produces too much androgen hormone, which affects ovulation. PCOS is also associated with insulin resistance and obesity. Uterine fibroids. Fibroids are benign tumors in the wall of the uterus and are common in women in their 30s and 40s. Rarely, they may cause infertility by blocking the fallopian tubes. More often, fibroids interfere with proper implantation of the fertilized egg.

13. Prolactin (PRL) is under dual control from the hypothalamus, where dopamine serves as an inhibitory signal, preventing PRL secretion, and thyrotropin-releasing hormone (TRH), under some conditions, stimulates increased PRL production and release.

14. Causes of Hyperprolactinemia Physiological causes : Pregnancy . Other: Increased anterior pituitary hormone production. Impaired dopamine delivery or enhanced TRH signaling, or both. Some medications result in increased PRL production through their anti-dopaminergic properties. In some conditions, such as renal or hepatic insufficiency, PRL is cleared less rapidly from the systemic circulation, which results in increased blood levels of PRL. Hypothyroidism If a woman has an underactive thyroid gland, the hypothalamus will secrete hormones to try to stimulate the thyroid gland. This same hormone may also cause excess prolactin to be produced from the pituitary. Treatment with thyroid hormone supplements will result in correction of both the thyroid and the high prolactin levelsThe most common medications that do this are known as anti-psychotic medications.  Other medications which may increase prolactin levels:Some types of anti-depressants Some types of sedatives Estrogen Oral contraceptives (birth control pills) Some types of blood pressure medications (methyldopa, verapamil) A medication for nausea (Reglan, metoclopramide) Antacids (cimetidien)  1-During pregnancy, a woman's body ramps up the production of prolactin, sometimes as much as ten times the amount prior to pregnancy.

16. Hyperprolactinemia and Infertility