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INFERTILITY HORMON DISORDER

PROGRAM KBK FK-UKI

Prof. Dr. drh. Maria Bintang, MS


GURU BESAR BIOKIMIA

REFERENCES

American society for reproductive medicine. 2008. Canadian Family Physician VOL 38: February 1992 Endocrinology. Vol. 142, No. 10 4272-4281. 2001 Journal of Lipid Research, Vol. 44, 154-163, January 2003 JCPSP, Vol. 17 (4): 191-194. 2007 J Obstet Gynecol India Vol. 56, No. 1 : January/February 2006 Lehninger. 2000. Principles of biochemistry 3rd Ed. Michael W. King. 2006. Medical Biochemistry. Murray R K, Granner D k, Mayers P a & Rodwell V w. 2003. Harpers Illustrated Biochemistry. 26th Ed. Pratt,C.W.and Cornely K. 2004. Essential Biochemistry. Wiley International Edition. Stryer, Lubert 1995. Biochemistry.4th Ed.

Androgen

Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and development of male secondary sex characteristics. Androgens, which were first discovered in 1936, are also called androgenic hormones or testoids. Androgens are also the original anabolic steroids. They are also the precursor of all estrogens, the female sex hormones. The primary and most well-known androgen is testosterone. The principal androgens are testosterone and androstenedione. They are, of course, present in much higher levels in men and play an important role in male traits and reproductive activity.

Besides testosterone, other androgens include: Dehydroepiandrosterone (DHEA): a steroid hormone produced in the adrenal cortex from cholesterol. It is the primary precursor of natural estrogens DHEA is also called dehydroisoandrosterone or dehydroandrosterone. Androstenedione (Andro): an androgenic steroid produced by the testes, adrenal cortex , and ovaries. While androstenediones are converted metabolically to testosterone and other androgens, they are also the parent structure of estrone. Use of androstenedione as an athletic or body building supplement has been banned by the International Olympic Committee as well as other sporting organizations.

Androstenediol: the

steroid metabolite that is thought to act as the main regulator of gonadotropin secretion. Androsterone: a chemical by-product created during the breakdown of androgens, or derived from progesterone, that also exerts minor masculinising effects, but with one-seventh the intensity of testosterone. It is found in approximately equal amounts in the plasma and urine of both males and females. Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen receptors. It is produced in the adrenal cortex.

Androgen functions
a. Development of the male Testis formation Androgen production Androgen effects Early regulation b. Spermatogenesis c. Inhibition of fat deposition d. Muscle mass e. Brain

Pathway of androgens

Testosteron Biosynthesis

Like other steroid hormones, testosterone is derived from cholesterol. The largest amounts of testosterone are produced by the testes in men. It is also synthesized in smaller quantities in women by the thecal cells of the ovaries, by the placenta, as well as by the zona reticularis of the adrenal cortex in both sexes. In the testes, testosterone is produced by the Leydig cells. The male generative glands also contain Sertoli cells which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone binding globulin (SHBG).

Pathway of Testosterone Biosynthesis

Dihydrotestosterone in Peripheral Tissues

Testosterone is metabolized by two pathways. One involves oxidation at the 17 position, and the other involves reduction of the A ring double bond and the 3ketone. Metabolism by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that are generally inactive or less active than the parent compound. Metabolism by the second pathway, which is less efficient, occurs primarily in target tissues and produces the potent metabolite dihydrotestosterone (DHT). The most significant metabolic product of testosterone is DHT, since in many tissues, including prostate, external genitalia, and some areas of the skin,this is the active form of the hormone.

The plasma content of DHT in the adult male is about one-tenth that of testosterone, and approximately 400 g of DHT is produced daily as compared with about 5 mg of testosterone. About 50100 g of DHT are secreted by the testes. The rest is produced peripherally from testosterone in a reaction catalyzed by the NADPH-dependent 5reductase Testosterone can thus be considered a prohormone, since it is converted into a much more potent compound (dihydrotestosterone) and since most of this conversion occurs outside the testes. Some estradiol is formed from the peripheral aromatization of testosterone, particularly in males.

Estrogen

Estrogens (alternative spellings: oestrogens) are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone. Estrogens are used as part of some oral contraceptives, in estrogen replacement therapy of postmenopausal women, and in hormone therapy for transsexual women. Like all steroid hormones, estrogens readily diffuse across the cell membrane; inside the cell, they interact with estrogen receptors A range of synthetic and natural substances have been identified that also possess estrogenic activity. Synthetic substances of this kind are known as xenoestrogens, while natural plant products with estrogenic activity are called phytoestrogens.

Types of estrogen The three major naturally occurring estrogens in women are estradiol, estriol, and estrone. In the body these are all produced from androgens through actions of enzymes. From menarche to menopause the primary estrogen is 17-estradiol. In postmenopausal women more estrone is present than estradiol. Estradiol is produced from testosterone and estrone from androstenedione. Estrone is weaker than estradiol.

Estriol

Estradiol

Estrone

Estrogens Functions

While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sex characteristics, such as breasts, and are also involved in the thickening of the endometrium and other aspects of regulating the menstrual cycle. Role in cancer About 80% of breast cancers, once established, rely on supplies of the hormone estrogen to grow: they are known as hormonesensitive or hormone-receptor-positive cancers. Suppression of production in the body of estrogen is a treatment for these cancers. In males estrogen regulates certain functions of the reproductive system important to the maturation of sperm and may be necessary for a healthy libido

Furthermore, there are several other structural changes induced by estrogen, in addition to other functions. Structural - promote formation of female secondary sex characteristics - accelerate height growth - accelerate metabolism (burn fat) - reduce muscle mass - stimulate endometrial growth - increase uterine growth - maintenance of vessel and skin - reduce bone resorption, increase bone formation - morphic change (endomorphic -> mesomorphic -> ectomorphic) Protein synthesis increase hepatic production of binding proteins Coagulation increase circulating level of factors, antithrombin III, plasminogen increase platelet adhesiveness

Lipid increase HDL, triglyceride, height growth decrease LDL, fat depositition Fluid balance salt (sodium) and water retention increase growth hormone increase cortisol, SHBG Gastrointestinal tract reduce bowel motility increase cholesterol in bile Melanin increase pheomelanin, reduce eumelanin Cancer support hormone-sensitive breast cancers Lung function promotes lung function by supporting alveoli (in rodents but probably in humans)

Estrogen production

Estrogen is produced primarily by developing follicles in the ovaries, the corpus luteum, and the placenta. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the production of estrogen in the ovaries. Some estrogens are also produced in smaller amounts by other tissues such as the liver, adrenal glands, and the breasts. These secondary sources of estrogen are especially important in postmenopausal women.

Synthesis of estrogens starts in theca interna cells in the ovary, by the synthesis of androstenedione from cholesterol. Androstenedione is a substance of moderate androgenic activity. This compound crosses the basal membrane into the surrounding granulosa cells, where it is converted to estrone or estradiol, either immediately or through testosterone. The conversion of testosterone to estradiol, and of androstenedione to estrone, is catalyzed by the enzyme aromatase. Estradiol levels vary through the menstrual cycle, with levels highest just before ovulation

Pathway of Estrogen Biosynthesis

Synthesis Progesteron

Progesterone, like all other steroid hormones, is synthesized from pregnenolone, a derivative of cholesterol. This conversion takes place in two steps. The 3-hydroxyl group is converted to a keto group the double bond is moved to C-4, from C-5. Progesterone is the precursor of the mineralocorticoid aldosterone, and after conversion to 17-hydroxyprogesterone (another natural progestogen) of cortisol and androstenedione. Androstenedione can be converted to testosterone, estrone and estradiol.

Pathway of Progesterone Biosynthesis

Progesterone is important for aldosterone (mineralocorticoid) synthesis, as 17-hydroxyprogesterone is for cortisol (glucocorticoid), and androstenedione for sex steroids

Female Infertility

Define infertility as a couple not able to conceive at the end of two years of adequate opportunities Infertility describes a person's biological inability to contribute to conception. Infertility can also describe a woman's inability to carry a pregnancy to full term. Causes:

Anovulation: this means failure on the part of the ovary to produce ova (egg). Frequently the common reasons are cyst in ovary, hypothyroidism, hormonal disturbances, some sex chromosome disorders and advanced age. Tubal Factor: bilateral tubal obstruction accounts for nearly 10% of cases. Tuberculosis, other infections, appendix, or previous operations can distort and occlude the tubes. Uterine Factors: Tuberculosis, fibroids, or inadequately formed endometrium lining of the uterus. Cervical Factors: cervical mucous hostility can obstruct the accent of sperm, thus causing infertility. Coital errors, use of lubricants, improper timing, anxiety.

Luteal Phase deficiency (LPD)

Luteal phase deficiencies can be caused by abnormal follicle development or abnormal luteinization. In both of these situations, the corpus luteum in the ovary follicle does not generate enough progesterone. Normally, the corpus luteum in the ovary luteinizing hormone (LH). LH causes the body to produce progesterone produces; a hormone which causes the thickening of the blood vessels in the uteral lining. These blood vessels form a protective, nourishing network, where the fertilized egg can develop into a baby. A lack of progesterone causes the blood vessel network to weaken and drop out of the uterine, ending the pregnancy. This is similar to what happens in a normal monthly period, when there is no pregnancy.

LPD is found in 3-20% of patients who are infertile and in 5-60% of patients who experience recurrent pregnancy loss. However, data show that 6-10% of women who are fertile also have an inadequate luteal phase. Luteal Phase Defect - In a luteal phase defect, a woman's corpus luteum - the mound of yellow tissue produced from the egg follicle - may fail to produce enough progesterone to thicken the uterine lining. Then the fertilized egg may be unable to implant. Medications - Many medicines, such as hormones, antibiotics, antidepressants, and pain killers may bring on temporary infertility. Commonly used medications such as aspirin and ibuprofen can also impair fertility if taken midcycle. Acetaminophen (Tylenol) pills can reduce the amount of estrogen and luteinizing hormones in the body, impairing fertility.

Human chorionic gonadotropin (hCG) is similar to LH; it contains equal amounts of LH and FSH. These hormones play a central role in egg production. In women. Luteinizing hormone (LH) and folliclestimulating hormone (FSH) are necessary for egg production (ovulation). Early in the menstrual cycle, a woman with low hormone levels who is not ovulating can have daily human menopausal gonadotropin (hMG) or recombinant human FSH (rFSH) injections for an average of 12 days. If this helps develop mature follicles, the ovary is ready to ovulate. One dose of human chorionic gonadotropin (hCG) is then used to stimulate ovulation.

Gonadotropin

The gonadotropin secretory pattern of anorexia nervosa patients is similar to the prepubertal pattern. When gonadotropin-releasing hormone (GnRH) is administered to patients with 53%-64% of their ideal body weight (IBW), they have a weak luteinizing hormone (LH) response and a normal follicle-stimulating hormone (FSH) response. As their weight increases, the LH response becomes stronger, and at 90%-94% of their IBW, the LH response is frequently exaggerated. Other studies indicate that an exaggerated LH response also occurs when GnRH is administered to fashionably slim women

In women gonadotropins may be used : To stimulate ovulation related to low natural gonadotropin or estrogen levels. (This is most commonly seen in women with excessive exercise or eating disorders.) Clomiphene and metformin have been ineffective for correcting irregular or no ovulation caused by polycystic ovary syndrome (PCOS). For developing multiple egg follicles on the ovaries. Multiple eggs are harvested and used in assisted reproductive techniques such as in vitro fertilization or gamete intrafallopian transfer. In combination with intrauterine insemination for couples with unexplained infertility when clomiphene has not worked.

THYROID DYSFUNCTION IN INFERTILE WOMEN

Thyroid is an important endocrine gland and its dysfunctions interfere with numerous aspects of reproduction and pregnancy Thyroid hormones receptors and their mRNA have been detected in human granulosa cells and direct effects of iodine and thyroid hormone on ovarian function are proposed recently. There is a known association of hyperthyroidism and hypothyroidism with menstrual disturbance, anovulatory cycles and decreased fecundity.

A number of studies have high lighted the role of thyroid dysfunction in female infertility hypothalamic-pituitarythyroid axis in such infertile women is less sensitive and they had compensated thyroid hormone profile with tissue hypothyroidism.
Such thyroid under function can affect female reproductive physiology indirectly in a number of ways: altering the pituitaryovarian axis, decreasing the binding activity of sex hormone binding globulin (SHBG) resulting in increased serum-free testosterone and estradiol, decreasing the metabolic clearance of androstenedione and estrone and increasing TRH levels resulting in increased prolactin levels and a delayed LH response to LH-releasing hormone.

The higher conception rate after thyroxine supplementation in infertile women with increased TSH verifies the presence of tissue hypothyroidism in such women Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH level below 2.5 mIU/L. In a comparison of infertile women with different females, the reasons of infertility has revealed that ovulatory dysfunction is particularly associated with hypothyroidism and increased TSH levels

Hyperprolactinemia

Excessive secretion of prolactin - hyperprolactinemia - is a relatively common disorder in humans. This condition has numerous causes, including prolactin-secreting tumors and therapy with certain drugs. Common manifestations of hyperprolactinemia in women include amenorrhea (lack of menstrural cycles) and galactorrhea (excessive or spontaneous secretion of milk). Hyperprolactinemic states result in hypogonadism through inhibition of gonadotropin secretion and suppression of gonadal steroidogenesis. Anovulation usually results when immunoreactive prolactin concentrations exceed 60 pg/L, but ovulatory cycles can persist in about 5% of hyperprolactinemic women, because the prolactin's biologic action in the circulation differs from its immunologic action.

Regulating prolactin secretion

Normal levels of prolactin range between 5 and 27 g/L(580 mIU/L) for women and between 5 and 15 g/L (450 mIU/L) for men. During pregnancy, levels rise; at term, mean maternal and umbilical cord plasma concentrations reach approximately 200 to 250 g/L. The prevalence of a prolactinoma is about 60% in women with prolactin levels higher than 100 g/L, and very high with prolactin levels higher than 250 g/L. Most of these are microadenomas (lesions less than 10 mm in diameter). The increase is a result of estrogen-induced hyperplasia of the lactotropes (the prolactin-secreting cells) in the pituitary gland.

The hypothalamus has an inhibitory action on prolactin release from the pituitary, mediated by a prolactin-inhibiting factor (PIF). The hormone prolactin is downregulated by dopamine and is upregulated by estrogen. Dopamine agonists (bromocriptine, levodopa, apomorphine) inhibits prolactin release; Dopamine receptor antagonists (phenothiazines, metoclopramide, pimozide) stimulate prolactin release There is a high incidence of hyperprolactinemia in infertile women. A positive correlation of 1:4 was found between hypothyroidism and hyperprolactinemia.

Polycystic Ovary Syndrome (Stein-Leventhal Syndrome)

Polycystic ovary syndrome (PCOS) is a hormone disorder that causes many small benign cysts to form on the ovaries under a thick, white covering, which prevents the release of an egg. It causes your menstrual cycle to be irregular, or you may have no periods at all. PCOS can make it hard for you to become pregnant The two ovaries are part of the female reproductive system, they produce eggs and the female hormones estrogen and progesterone. Ovarian cysts are fluid-filled sacs that form on the ovaries when the follicles (sacs) on the ovary that contain an egg mature but do not release the egg into the fallopian tube. Some women with polycystic ovary syndrome may have mildlyelevated prolactin levels.

PCOS increases your risk of uterine cancer, diabetes, and heart disease It is the most common cause of infertility, occurring in about ten percent of all women. The main symptoms include irregular ovulation and/or menstruation, weight problems, and too many masculine hormones. Irregular ovulation means that often there will not be eggs to be impregnated. Menstruation problems cause an actual pregnancy not to last. While the causes of PCOS are not known, obesity, diabetes and insulin resistance often accompany PCOS. Many physicians miss this, so one should search for a physician who is experienced with this. For overweight women, weight loss can improve the condition

How does PCOS occur


Studies

are looking at whether it is caused by genetics. Also, because many women with PCOS also have diabetes, studies are examining the relationship between PCOS and the level of insulin in the body. High levels of insulin appear to cause the body to make more of the male hormone testosterone, which worsens the symptoms of PCOS. A problem called insulin resistance (inefficient use of insulin in the body) can cause the high levels of insulin. Too much insulin in the body increases the risk for other problems, such as obesity, diabetes, high blood pressure, and heart disease.

The PCOS symptoms include:


Irregular menstrual periods, particularly long cycles, or no periods at all Very light or very heavy bleeding during your period Trouble getting pregnant More hair on your face, chest, and lower abdomen Balding in some women Obesity Acne.

Hydatidiform mole
Molar pregnancy is an abnormal form of pregnancy, characterized by the presence of a hydatidiform mole (or hydatid mole, mola hytadidosa), an anomalous growth containing a nonviable embryo which implants and proliferates within the uterus. A hydatidiform mole is removed upon diagnosis because there is some risk that it develop into choriocarcinoma, a form of cancer. A hydatidiform mole is a pregnancy/conceptus in which the placenta contains grapelike vesicles that are visible with the naked eye The vesicles arise by distention of the chorionic villi by fluid. When inspected in the microscope, hyperplasia of the trophoblastic tissue is noted. If left untreated, a hydatidiform mole always ends as a spontaneous abortion.

Potential risk factors may include defects in the egg, abnormalities within the uterus, or nutritional deficiencies. Women under 20 or over 40 years of age have a higher risk. Other risk factors include diets low in protein, folic cid, and carotene The diploid set of sperm-only DNA means that all chromosomes have sperm-patterned methylation suppression of genes. This leads to overgrowth of the syncytiotrophoblast whereas dual egg-patterned methylation leads to a devotion of resources to the embryo, with an underdeveloped syncytiotrophoblast. This is considered to be the result of evolutionary competition with male genes driving for high investment into the fetus versus female genes driving for resource restriction to maximise the number of children

Treatment of Hydatidiform mole


Hydatidiform moles should be treated by evacuating the uterus by uterine suction or by surgical curettage as soon as possible after diagnosis, in order to avoid the risks of choriocarcinoma. Patients are followed up until their serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level. Invasive or metastatic moles (cancer) may require chemotherapy and often respond well to methotrexate. The response to treatment is nearly 100%. Patients are advised not to conceive for one year after a molar pregnancy. The chances of having another molar pregnancy are approximately 1%. Management is more complicated when the mole occurs together with one or more normal fetuses.

Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions, of which monosomy X is the most common. It occurs in about 1 out of every 2500 female births. Instead of the normal XX sex chromosomes for a female, only one X chromosome is present and fully functional; in rarer cases a second X chromosome is present but abnormal, while others with the condition have some cells with a second X and other cells without it (mosaicism). A normal female karyotype is labeled 46,XX; individuals with Turner syndrome are 45,X. In Turner syndrome, female sexual characteristics are present but generally underdeveloped. Nearly all girls with Turner syndrome will be infertile, or unable to become pregnant on their own.

Other effects Can Turner Syndrome Have: Kidney problems, High blood pressure, heart problems, overweight, hearing difficulties, Diabetes, cataracts, Tyroid promlems. Some girls with the condition may experience learning difficulties, particularly in math. Many have a difficult time with tasks that require skills such as map reading or visual organization.

How Is Turner Syndrome Treated


Growth hormone treatment can improve growth and influence a girl's final adult height. In fact, in many cases, the treatment can help many girls with Turner syndrome reach a final height in the average range, especially if treatment is started early enough Another treatment for Turner syndrome is estrogen replacement, which helps the girl develop the physical changes of puberty (12-13 years old), including breast growth and eventually menstrual periods. And a technique called in vitro fertilization can make it possible for some women with Turner syndrome to become pregnant. A donor egg can be used to create an embryo, which is then put into the uterus (womb) of the woman with Turner syndrome. With proper supportive care, the woman can carry the pregnancy to term and deliver a baby through the normal birth process. Girls with Turner syndrome are usually short in height. Girls with Turner syndrome who aren't treated reach an average height of about 4 feet 7 inches (1.4 meters). The good news is that when Turner syndrome is diagnosed while a girl is still growing, she can be treated with hormones to help her grow taller.

Common symptoms of Turner syndrome include:


Short stature Lymphoedema (swelling) of the hands and feet Broad chest (shield chest) and widely-spaced nipples Low hairline Low-set ears Reproductive sterility (infertility) Rudimentary ovaries gonadal streak (underdeveloped gonadal structures) Amenorrhea, or the absence of a menstrual period Increased weight, obesity Shield shaped thorax of heart Shortened metacarpal IV (of hand) Small fingernails Characteristic facial features Webbing of the neck (webbed neck) Coarctation of the aorta Poor breast development Horseshoe kidney Visual impairments sclera, cornea, Glaucoma, Drooping eyelids, Dry eyes Ear infections and hearing loss.

Risk factors
Risk factors for Turner syndrome are not well known. Nondisjunctions increase with maternal age, such as for Down syndrome, but that effect is not clear for Turner syndrome. It is also unknown if there is a genetic predisposition present that causes the abnormality, though most researchers and doctors treating Turners women agree that this is highly unlikely. There is currently no known cause for Turner syndrome, though there are several theories surrounding the subject.

Cause of Turner syndrome


Turner syndrome because the number of individuals studied within the less common karyotype groups is too small. Other studies also suggest the presence of hidden mosaicisms that are not diagnosed on usual karyotypic analyses in some patients with 45,X karyotype. Thyroid disease is interrelated with women's hormones, and can have an impact on menstrual cycles, fertility, estrogen/progesterone levels, successful pregnancy, and the ability to breastfeed and menopause. Hypothyroidism in pregnancy can have adverse effects for the child's development Thyroid problems after pregnancy occur in as many as 10 percent of all new mothers.

INFERTILITY IN MEN

A variety of disorders ranging from hormonal disturbances to physical problems, to psychological problems can cause male infertility. Although many treatment options are now available, in many cases treatment will not work. In many instances, male infertility is caused by testicular damage resulting in an inability of the testicle to produce sperm. Once damaged, the testicle will not usually regain its spermmaking capabilities; this aspect of male infertility is analogous to menopause (though not natural like menopause) for women and cannot usually be treated. Despite medicines limited ability to treat male infertility, many successful treatment options are available for its many causes.

Besides testicular damage, the main causes of male infertility are low sperm production and poor sperm quality. Endocrine evaluation includes measurement of follicle stimulating hormone (FSH) and testosterone.Luteinizing hormone (LH), estradiol,and prolactin are also commonly measured. The function of the testes is dependent upon hormones from the pituitarygland - follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones rises during the early stages of puberty and stimulates testicular development. LH controls production of the male sex hormone testosterone which in turn is responsible for development of the genitals, beard and body hair, prostate and seminal vesicles, and also bone and muscle development and other aspects of masculine physique.

If LH and FSH are deficient the testes do not develop properly. In contrast, if the testes are damaged directly, the levels of these hormones in the blood rise. Thus the measurement of LH, FSH and testosterone in blood helps in the diagnosis of testicular disorders. Deficiency of two hormones from the pituitary gland, LH and FSH, can be treated by injection or hormone preparations. In men with low testosterone and FSH, LH stimulates the production of testosterone, and FSH promotes the formation of sperm. If a semen analysis, LH, and FSH testing suggest that abnormal hormone levels are preventing sperm production, these gonadotropins may be prescribed to promote sperm formation together.

hCG (Human chorionic gonadotropin) is injected 3 times weekly until blood testosterone level is within the normal range (this may take 4 to 6 months). Treatment continues with injections of hCG twice a week and hMG or FSH 3 times a week until the sperm count rises to normal levels. Rarely, a hormonal difficulty that decreases or stops the man's production of sperm. Hormonal problems may be present from birth or can develop from brain or pituitary gland tumors or radiation treatment. Sometimes, hormonal difficulties are induced by excessive exercise, malnutrition or other illnesses

Hormone-sensitive lipase (HSL)


The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters (CEs). The enzyme is highly expressed in adipose tissues (ATs), where it is thought to play an important role in fat mobilization.

The Causes of Male Infertility

Male infertility has many causes-from: hormonal imbalances physical problems, psychological and/or behavioral problems. Moreover, fertility reflects a mans overall health. Men who live a healthy lifestyle are more likely to produce healthy sperm. Modifying these behaviors can improve a mans fertility and should be considered when a couple is trying to achieve pregnancy.

Some lifestyle choices that negatively impact male fertility it is not all-inclusive:
Smoking significantly decreases both sperm count and sperm cell motility. Prolonged use of marijuana and other recreational drugs. Chronic alcohol abuse. Anabolic steroid use--causes testicular shrinkage and infertility. Overly intense exercise produces high levels of adrenal steroid hormones which cause a testosterone deficiency resulting in infertility. Inadequate vitamin C and Zinc in the diet. Tight underwear increases scrotal temperature which results in decreased sperm production. Exposure to environmental hazards and toxins such as pesticides, lead, paint, radiation, radioactive substances, mercury, benzene, boron, and heavy metals Malnutrition and anemia. Excessive stress!

Hormonal Problems

A small percentage of male infertility is caused by hormonal problems. The hypothalamus-pituitary endocrine system regulates the chain of hormonal events that enables testes to produce and effectively disseminate sperm. Several things can go wrong with the hypothalamus-pituitary endocrine system:

The brain can fail to release gonadotrophic-releasing hormone (GnRH) properly. GnRH stimulates the hormonal pathway that causes testosterone synthesis and sperm production. A disruption in GnRH release leads to a lack of testosterone and a cessation in sperm production. The pituitary can fail to produce enough lutenizing hormone (LH) and follicle stimulating hormone (FSH) to stimulate the testes and testosterone/sperm production. LH and FSH are intermediates in the hormonal pathway responsible for testosterone and sperm production. The testes Leydig cells may not produce testosterone in response to LH stimulation. A male may produce other hormones and chemical compounds which interfere with the sex-hormone balance.

Hormonal disorders which can disrupt male infertility:


1. 2. 3. 4. 5.

Hyperprolactinemia Hypothyroidism Congenital Adrenal Hyperplasia Hypogonadotropic Hypopituitarism Panhypopituitarism

1. Hyperprolactinemia: Elevated prolactin-a hormone associated with nursing mothers, is found in 10 to 40 percent of infertile males Mild elevation of prolactin levels produces no symptoms, but greater elevations of the hormone reduces sperm production, reduces libido and may cause impotence. This condition responds well to the drug Parlodel (bromocriptine). Men with hyperprolactinemia typically show hypogonadism, with decreased sex drive, decreased sperm production and impotence. Such men also often show breast enlargement (gynecomastia), but very rarely produce milk.

2.

Hypothyroidism: Low thyroid hormone levels can cause poor semen quality, poor testicular function and may disturb libido. May be caused by a diet high in iodine. Reducing iodine intake or beginning thyroid hormone replacement therapy can elevate sperm count. This condition is found in only 1 percent of infertile men. Congenital Adrenal Hyperplasia: Low thyroid hormone levels can cause poor semen quality, poor testicular function and may disturb libido. May be caused by a diet high in iodine. Reducing iodine intake or beginning thyroid hormone replacement therapy can elevate sperm count. This condition is found in only 1 percent of infertile men.

3.

4.

Hypogonadotropic Hypopituitarism:
Low pituitary gland output of LH and FSH. This condition arrests sperm development and causes the progressive loss of germ cells from the testes and causes the seminiferous tubules and Leydig (testosterone producing) cells to deteriorate. May be treated with the drug Serophene. However, if all germ cells are destroyed before treatment commences, the male may be permanently infertile.

5.

Panhypopituitarism:
Complete pituitary gland failure--lowers growth hormone, thyroidstimulating hormone, and LH and FSH levels. Symptoms include: lethargy, impotence, decreased libido, loss of secondary sex characteristics, and normal or undersized testicles. Supplementing the missing pituitary hormones may restore vigor and a hormone called hCG may stimulate testosterone and sperm production.

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