Anti- androgen therapy . Updated 2. 3 February 2. There are a range of weight loss injections, so how do you know which are the best weight loss shots for you? Find out here with detailed reviews on each. February 2014 Issue. PCOS in Aging Women — Beyond Hormones and Hot Flashes By Angela Grassi, MS, RDN, LDN Today’s Dietitian Vol. How to Ovulate With PCOS. If you suffer from Polycystic Ovary Syndrome (PCOS), you're not alone. Between 5-10% of American women of childbearing age are estimated to. Prescription Medications & Weight Gain – What You Need to Know by Ted Kyle, RPh, MBA, and Bonnie Kuehl, PhD. To view a PDF version of this article, click here. Male Infertility Overview Assessment, Diagnosis, and Treatment. Shaban, M.D. Clinical Assistant Professor Department of Surgery, Division of Urology. What is anti- androgen therapy? Anti- androgen therapy refers to medication taken by women to counteract the effect of male sex hormones such as testosterone on the skin. Anti- androgens are not suitable for skin problems in men. What are anti- androgens used for? Anti- androgen medications are used to treat signs of hyperandrogenism, including the following skin and hair disorders: How does anti- androgen therapy work? Anti- androgen therapy may: Block androgen receptor. Reduce adrenal androgen production. Reduce ovarian androgen production. Reduce pituitary production of prolactin. Inhibit 5- alpha reductase (this enzyme acts in the skin to increase dihyroxytestosterone)Reduce insulin resistance. Which drugs have anti- androgenic action? Androgen receptor blockers act on the sebaceous gland and base of the hair follicle. They include: Oral contraceptive (birth control pill) containing ethinylestrodiol (oestrogen) and an antiandrogenic progesterone. These include cyproterone acetate (co- cyprindiol or Diane. These contain ethinylestrodiol and desorgestrel, gestodene or norgestimate. Spironolactone 2. Aldactone. Cyproterone acetate 5. Androcur. This powerful anti- androgen is usually taken on days 1 to 1. Flutamide 2. 50- 5. This is normally used as a hormonal antineoplastic agent in males with prostate cancer. It can cause hepatitis and should not be used for skin disorders. Spironolactone and cyproterone may be effectively combined with cyproterone acetate/ethinyloestradiol or other oral contraceptive agent, partly because they cause menstrual irregularities and partly to prevent pregnancy. The combined treatment is not necessary in post- menopausal women. Low- dose oral corticosteroid (eg prednisone 2. In congenital adrenal hyperplasia, DHEAS levels should reduce to normal. Limecycline, roxithromycin and ketoconazole (no longer available in New Zealand) are antimicrobial drugs that have also been noted to reduce androgen synthesis. Drugs acting on ovarian androgen production include: Gonadotrophin receptor hormone (Gn. RH) agonist (buserelin, leuprolide), which stop ovulation and suppress androgen production. Because they also stop oestrogen production, they may lead to menopausal symptoms, headache and osteoporosis. Combined oral contraceptives. Progestins. Excessive prolactin is reduced by bromocriptine, cabergoline and quinagolide. Spironolactone inhibits 5- alpha reductase weakly. Unfortunately, finasteride does not reduce sebum production and is not effective in the treatment of acne. However, we now know that isotretinoin reduces sebum partly by reducing dihyrotestosterone production in the sebaceous gland. Insulin resistance can be reduced using metformin, mainly prescribed for type 2 diabetes mellitus and obesity / metabolic syndrome. It may also reduce signs of hyperandrogenism. Metformin 2. 50 mg to 2 g daily is safe but can cause diarrhoea and should be taken after food in gradually increasing doses. Rosiglitazone and pioglitazone can cause heart and liver toxicity. What are the clinical effects of anti- androgen therapy? In acne, the effects of anti- androgens include: They can be combined with other topical and oral treatments for acne. In hirsutism, the results are: Slower growth of hair. Lighter coloured hair. Finer textured hair. Physical methods of hair removal such as waxing, shaving, electrolysis or laser epilation, can be used at the same time as anti- androgens are taken. They often work better than prior to the medication. In female pattern hair loss, the results are: Reduced hair shedding. Reduced hair thinning. Sometimes, restoration of thicker hair. These effects are not always clinically significant. Oral contraceptives. Progesterone- only oral contraceptives are not effective in the management of androgen- mediated skin conditions. Combined oral contraceptives contain two hormones, ethinyloestrodiol 2. They prevent pregnancy by suppressing ovulation and changing cervical mucus. There are various kinds of progesterone, which may be androgenic in nature and thus unsuitable for those androgen- mediated skin conditions (particularly levonorgesterol and norgestrel). Anti- androgenic or minimally androgenic progesterones (see above) are indicated in these women. Their effect in hyperandrogenism is to reduce production of androgens by the ovaries, by the adrenals and at the receptor level in the skin. They also decrease circulating testosterone by increasing sex hormone binding globulin (SHBG). Combined oral contraceptives are available as 2. Day 1 (conventionally, day 1 is the first day of menstruation) and take one a day for 2. Then have a 7- day break (2. During this time, you can expect a withdrawal bleed (a period). Combined oral contraceptives can increase the risk of thromboembolism (blood clots blocking blood vessels), especially in those with an inherited tendency (. Please refer to the New Zealand Ministry of Health (Medsafe) advice on the use of combined oral contraceptives. The combined oral contraceptive may be unsuitable if the patient: Has had a previous blood clot (thrombosis, embolism or . They may occasionally increase the risk of certain uncommon forms of breast cancer. They must not be taken in pregnancy. On the other hand, the combined oral contraceptive reduces the risk of ovarian and endometrial cancer, benign breast disease, ectopic pregnancy, painful periods, iron deficiency anaemia and pelvic inflammatory disease. Cyproterone acetate/ethinyloestradiol (co- pyrindiol) should be discontinued in the following circumstances: Severe migraine (headache, visual disturbance, numb feelings)Any form of thrombosis (such as heart attack, stroke) or increased blood pressure. In case of immobility (including due to surgery) or trauma (eg bad sprains)If an increase in number or severity of epileptic seizures occurs, or liver disease arises during treatment. Pregnancy. As with other oral contraceptives, minor side effects may arise, especially in the first few weeks. These include: Breast tenderness (2. Rarely, periods may stop altogether (amenorrhoea). If you have spotting (bleeding in between periods), see your doctor. He or she may advise you to take the active medication continuously for 3 months or more. This is quite safe and often prevents unwanted bleeding. Nausea, loss of appetite and bloating. Headaches. Increased appetite and weight increase (uncommon)Mood changes including depression and reduced libido Melasma (facial pigmentation)Hair loss (it is more common for hair fall to occur when the medication has been discontinued however)Acne. Other medications can interfere with the contraceptive effectiveness. Combined oral contraceptives with anti- androgenic components have advantages: They regulate the menstrual cycle in the majority of women. Lighter, less painful periods occur in the majority of women. Iron deficiency anaemia is less common because of less bleeding. Increased . Combined oral contraceptives can usually be taken safely for many years. Unfortunately, the skin condition tends to deteriorate again within a few months after the medication has been stopped. New forms of oral contraceptive are introduced from time to time, to increase efficacy and reduce side effects. Please refer to the New Zealand Ministry of Health (Medsafe) advice on the use of combined oral contraceptives. Spironolactone. Spironolactone is a potassium- sparing medication used as a diuretic medication for heart failure, liver disease and high blood pressure. However, it has also been found useful for hirsutism, acne and seborrhoea because it has anti- androgenic properties. Spironolactone mainly works by blocking androgen receptors. The dose of spironolactone is usually slowly increased from 2. It is sometimes prescribed cyclically to reduce menstrual irregularities, eg, for 3 weeks out of every 4 weeks or days 5–2. It may take six or more months to see improvement in the skin condition. Side effects of spironolactone include: Nausea, diarrhoea, gastrointestinal bleeding. Drowsiness (possibly due to high blood potassium levels)Headache and dizziness. Menstrual cycle irregularities including increased frequency of menstruation, bleeding in the middle of the month or stopping periods altogether (amenorrhoea)Breast pain. Potassium, other electrolytes and creatinine levels in the blood are often monitored. This is especially necessary in older women, if high doses are prescribed, in patients taking other medicines (due to drug interactions) and in those with heart or kidney problems. Spironolactone should not be taken in pregnancy or during lactation. Serum potassium should be . Cyproterone acetate. Higher doses of cyproterone acetate are indicated for more severe cases of androgenetic skin conditions. It is effective for 7. Several different regimes are prescribed with doses ranging from 2. Prior to the menopause, the medication is usually combined with cyproterone acetate/ethinyloestradiol or other oral contraceptive agent: To regulate menstrual cycle irregularities caused by the high dose cyproterone. To prevent pregnancy; there are concerns that cyproterone could harm a male fetus by . It may be advisable to have a 7- day break every month. They may also take spironolactone. Occasional significant side effects include: Liver disturbance. Tiredness and depression. Weight increase. Related information. Male Infertility Overview. Male Infertility Overview. Assessment, Diagnosis, and Treatment. Stephen F. Shaban, M. D. Clinical Assistant Professor. Department of Surgery, Division of Urology. University of North Carolina School of Medicine. Chapel Hill, NC. Most authorities define these patients as primarily infertile if they have been unable to achieve a pregnancy after one year of unprotected intercourse. Conception normally is achieved within twelve months in 8. Data available over the past twenty years reveal that in approximately 3. Therefore, the male factor is at least partly responsible in about 5. It is extremely important in the evaluation of infertility to consider the couple as a unit in evaluation and treatment and to proceed in a parallel investigative manner until a problem is uncovered. It has been shown that the longer a couple remains subfertile, the worse their chance for an effective cure. Many couples experience significant apprehension and anxiety after only a few months of failure to conceive. Unduly prolonged unprotected intercourse should not be advocated before a workup of the man is instituted. Initial screening of the man should be considered whenever the patient presents with the chief complaint of infertility. This initial evaluation should be rapid, non- invasive and cost effective. Of interest is the fact that pregnancy rates of up to 5. MALE REPRODUCTIVE PHYSIOLOGYThe Hypothalamic- Pituitary- Gonadal Axis. The hypothalamus is the integrative center of the reproductive axis and receives messages from both the central nervous system and the testes to regulate the production and secretion of gonadotropin releasing hormone (Gn. RH). Neurotransmitters and neuropeptides have both inhibitory and stipulatory influence on the hypothalamus. The hypothalamus releases Gn. RH in a pulsatile nature which appears to be essential for stimulating the production and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH). Interestingly and paradoxically, after the initial stimulation of these gonadotropins, the exposure to constant Gn. RH results in inhibition of their release. LH and FSH are produced in the anterior pituitary and are secreted episodically in response to the pulsatile release of Gn. RH. LH and FSH both bind to specific receptors on the Leydig cells and Sertoli cells within the testis. Testosterone, the major secretory product of the testes, is a primary inhibitor of LH secretion in males. Testosterone may be metabolized in peripheral tissue to the potent androgen dihydrotestosterone or the potent estrogen estradiol. These androgens and estrogens act independently to modulate LH secretion. The mechanism of feedback control of FSH is regulated by a Sertoli cell product called inhibin. Decreases in spermatogenesis are accompanied by decreased production of inhibin and this reduction in negative feedback is associated with reciprocal elevation of FSH levels. Isolated increased levels of FSH constitute an important, sensitive marker of the state of the germinal epithelium. In males with hyperprolactinemia, the prolactin tends to inhibit the production of Gn. RH. Besides inhibiting LH secretion and testosterone production, elevated prolactin levels may have a direct effect on the central nervous system. In individuals with elevated prolactin levels who are given testosterone, libido and sexual function do not return to normal as long as the prolactin levels are elevated. The Testes. Leydig; Cells. Testosterone is secreted episodically from the Leydig cells in response to LH pulses and has a diurnal pattern, with the peak level in the early morning and the trough level in the late afternoon or early evening. In the intact testis, LH receptors decrease or down- regulate after exogenous LH administration. Large doses of Gn. RH or its analogs can reduce the numbers of LH receptors and therefore inhibit LH secretion. This has been applied clinically to cause medical castration in men with prostate cancer. Estrogen inhibits some enzymes in the testosterone synthetic pathway and therefore directly effects testosterone production. There also appears to be an intratesticular ultra short loop feedback such that exogenous testosterone will override the effect of LH and inhibit testosterone production. In normal males, only 2% of testosterone is free or unbound. Te. BG, also called sex hormone- binding globulin. These steroid- binding proteins modulate androgen action. Te. BG has a higher affinity for testosterone than for estradiol, and changes in Te. BG alter or amplify the hormonal milieu. Te. BG levels are increased by estrogens, thyroid administration and cirrhosis of the liver and may be decreased by androgens, growth hormone and obesity. The biological actions of androgens are exerted on target organs that contain specific androgen receptor proteins. Testosterone leaves the circulation and enters the target cells where it is converted to the more potent androgen dihydrotestosterone by an enzyme 5- alpha- reductase. The major functions of androgens in target tissues include 1) regulation of gonadotropin secretion by the hypothalamic- pituitary axis; 2) initiation and maintenance of spermatogenesis; 3) differentiation of the internal and external male genital system during fetal development; and 4) promotion of sexual maturation at puberty. Seminiferous Tubules. The seminiferous tubules contain all the germ cells at various stages of maturation and their supporting Sertoli cells. These account for 8. Sertoli cells are a fixed- population of non- dividing support cells. They rest on the basement membrane of the seminiferous tubules. They are linked by tight junctions. These tight junctions coupled with the close approximation of the myoid cells of the peritubular contractile cell layers serve to form the blood- testis barrier. This barrier provides a unique microenvironment that facilitates spermatogenesis and maintains these germ cells in an immunologically privileged location. This isolation is important because spermatozoa are produced during puberty, long after the period of self- recognition by the immune system. If these developing spermatozoa were not immunologically protected, they would be recognized as foreign and attacked by the body's immune system. Sertoli cells appear to be involved with the nourishment of developing germ cells as well as the phagocytosis of damaged cells. Spermatogonia and young spermatocytes are lower down in the basal compartment of the seminiferous tubule, whereas mature spermatocytes and spermatids are sequestered higher up in the adluminal compartment. Spermatogonia lie directly on the basement membrane, and next in order, progressing up to the lumen, are found the primary spermatocytes, secondary spermatocytes and spermatids. There are felt to be 1. The spermatocytes eventually divide and give rise to mature cell lines that eventually give rise to spermatids. The spermatids then undergo a transformation into a spermatozoa. This transformation includes nuclear condensation, acrosome formation, loss of most of the cytoplasm, development of a tail and arrangement of the mitochondria into the middle piece of the sperm which basically becomes the engine room to power the tail. Groups of germ cells tend to develop and pass through spermatogenesis together. This sequence of developing germ cells is called a generation. These generations of germ cells are basically in the same stage of development. There are six stages of seminiferous epithelium development. The progression from stage one through stage six constitutes one cycle. In humans the duration of each cycle is approximately 1. Therefore, the duration of the entire spermatogenic cycle in humans is 4. LH effects spermatogenesis indirectly in that it stimulates androgenous testosterone production. FSH targets Sertoli cells. Therefore, testosterone and PSH are the hormones that are directed at the seminiferous tubule epithelium. Androgen- binding protein which is a Sertoli cell product carries testosterone intracellularly and may serve as a testosterone reservoir within the seminiferous tubules in addition to transporting testosterone from the testis into the epididymal tubule. The physical proximity of the Leydig cells to the seminiferous tubules and the elaboration by the Sertoli cells of androgen- binding protein, cause a high level of testosterone to be maintained in the microenvironment of the developing spermatozoa. The hormonal requirements for initiation of spermatogenesis appear to be independent of the maintenance of spermatogenesis. For spermatogenesis to be maintained like for instance after a pituitary obliteration, only testosterone is required. However, if spermatogenesis is to be re- initiated after the germinal epithelium has been allowed to regress completely, then both FSH and testosterone are required. Testicular spermatozoa are non- motile and were felt to be incapable of fertilizing ova. Spermatozoa gain progressive motility and fertilizing ability after passing through the epididymis. The coiled seminiferous tubules terminate within the rete testis, which in turn coalesces to form the ductuli efferentes. These ductuli efferentes conduct testicular fluid and spermatozoa into the head of the epididymis. The epididymis consists of a fragile single convoluted tubule that is 5- 6 meters in length. The epididymis is divided into the head, body, and tail. Although epididymal transport time varies with age and sexual activity, the estimated transit time of spermatozoa through the epididymis in healthy males is approximately four days. It is during the period of maturation in the head and body of the epididymis that the sperm develop the increased capacity for progressive motility and also acquire the ability to penetrate oocytes during fertilization. The epididymis also serves as a reservoir or storage area for sperm. It is estimated that the extragonadal sperm reservoir is 4.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. Archives
November 2017
Categories |