Chapter 18 The reproductive system Physiologic Concepts Spermatogenesis

1. Chapter 18 The reproductive system Physiologic Concepts Spermatogenesis Spermatogenesis (the formation of sperm) begins during puberty and continues throughout the lifetime of a male. Undifferentiated germ cells lining the seminiferous tubules undergo a programmed number of mitotic cell divisions, resulting in the production of the primary spermatocytes (immature sperm), which ultimately develop into the spermatozoa (mature sperm).

2. Spermatogenesis requires approximately 2 months. From each primary spermatocyte, four viable sperm (each with 23 chromosomes) are produced. Spermatogenesis occurs in the seminiferous tubule under the control of two pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and the sex hormones, primarily testosterone.

3. Follicle-Stimulating Hormone FSH is a protein hormone released from the anterior pituitary in response to a stimulating hormone from the hypothalamus: gona-dotropin-releasing hormone (GnRH) . The final effect of FSH is to cause proliferation and differentiation of the immature sperm. Luteinizing Hormone LH is the second protein hormone released from the anterior pituitary in response to stimulation by GnRH. LH stimulates the synthesis of the steroid hormone testosterone

4. Stimuli Controlling GnRH Release • GnRH is released in small pulses throughout the day, resulting in relatively constant daily levels. Increases or decreases in GnRH release may occur seasonally and with different physical and psychological conditions such as anxiety or depression. • Changes in the secretion of GnRH may affect sperm formation by affecting LH and FSH and may alter libido.

5. Male secondary sexual characteristics Male secondary sexual characteristics are under the control of the male androgens, especially testosterone. The male secondary sexual characteristics include the following: • Increased protein anabolism and muscle mass. • Increased bone growth and strength. • Male pattern of hair on the face, axillary, and pubic regions. Hair growth is thick on most areas of the body. • Increased metabolic rate, probably as a result of increased protein anabolism (buildup) and muscle mass formation. Increased metabolic rate raises the caloric needs of males, beginning at puberty, compared to females.

6. Proliferation and activation of sebaceous glands in the skin, which produce an oily substance called sebum. Increased amounts of sebum can cause acne, especially during teenage years. • A deepening voice, as a result of hypertrophy of the larynx. • Male pattern baldness, typically beginning with a bald spot on the top of the head. A genetic tendency influences male pattern baldness.

7. The Menstrual Cycle The menstrual cycle is the cyclic maturation and release of an ovum. It involves the growth of a follicle, ovulation of the ovum, and characteristic changes in the endometrial lining of the uterus. Ovulation On approximately day 12 of the menstrual cycle, there is a dramatic rise (6- to 10-fold) in the release of LH from the anterior pituitary. This rise is called a preovulatory LH surge. FSH increases to a lesser degree. Rising LH levels initiate a profound, final growth of the follicle, and then rupture, releasing the ovum into the abdominal cavity.

8. Female Secondary Sexual Characteristics The female secondary and associated sexual characteristics are under the control of estrogen and to a lesser extent progesterone .The female secondary sexual characteristics include: • Fully developed breasts. • The female pattern distribution of pubic hair. The growth of pubic and axillary hair in women is not estrogen dependent, but occurs as a result of adrenal gland androgen release.

9. Puberty Puberty is the beginning of sexual maturation. Puberty typically occurs at a younger age in girls than boys. It begins in girls between 8 and 14 years of age, and in boys between 10 and 16 years of age. The menstrual cycle is the culmination of puberty in girls. In boys, puberty culminates in the ability to ejaculate mature sperm. Menopause Menopause is defined only in retrospect, as a lack of menstrual cycles for the previous 12 months. It occurs in a woman when her ovaries no longer respond to LH and FSH with estrogen and progesterone production, and no longer release an ovum

10. Pathophysiologic Concepts Infertility Infertility is the inability or reduced ability to produce offspring. Infertility in a couple may result from female factors (40 to 50%), male factors (30 to 40%), or a combination (20%). Infertility in a couple may occur from the start of the relationship (primary infertility) or after the couple has already produced one or more offspring (secondary infertility).

11. Female Factors N.,B.Optimal fertility in women lasts to about 30 years of age and then begins to fall sharply with increasing frequency as a woman ages. - Problems with follicular growth, anovulation (failure to ovulate), or ovulatory irregularities. - Blockage of the fallopian tubes following pelvic infection • Presence of uterine abnormalities that prevent implantation may be involved. • Immune responses may destroy the implanted embryo if the woman is either hyperimmune to the embryo or fails to develop tolerance to it.

12. Miscarriages later in gestation may occur if the placenta is poorly placed or poorly perfused with blood, or if the cervix cannot support the weight of a growing fetus. • Treatmentof female infertility is specific to the cause. • Drugs to induce ovulation or superovulation (more than one ovum) may be administered. • Harvesting of eggs from the woman for in vitro fertilization (outside of the body) may be attempted. Eggs fertilized outside the body may be implanted into the fallopian tube or uterus.

13. Male Factors May include : -Defects in spermatogenesis that result in deformed sperm or sperm too few in number to allow for successful penetration of the ovum. -Sperm motility (movement) may be impaired as well. -Infection and scarring of the testicles, epididymis, vas deferens, or urethra. -Systemic infections, such as mumps, may cause swelling of the testicles and destruction of the seminiferous tubules.

14. -Obstruction of the blood vessels supplying the testes can cause hypoxia and a failure of the sperm to develop or survive. • Autoantibodiesproduced against sperm may reduce sperm number and quality. • Exposure of the testicles to high temperature may reduce spermatogenesis. • Treatment of male factor infertility is specific to the cause. For example, for a man with a low sperm count, sperm may be obtained via masturbation and then introduced artificially into his female partner after techniques to increase the concentration of the highest-quality sperm have been performed. This process is called artificial insemination.

15. Gynecomastia Gynecomastia is the enlargement of breast tissue in males. It can result from excess production of estrogen in the male or the liver's inability to break down normal male estrogen secretions. Gynecomastia is frequently seen during early puberty in some males and may be a normal development or may be related to excess body weight or a hormonal imbalance

16. Dysmenorrhea Is painful menstruation that occurs without evidence of pelvic infection or disease. It is usually caused by excessive release of a specific prostaglandin, from the uterine endometrial cells which is a potent stimulator of myometrial smooth muscle contraction and uterine blood vessel constriction causing significant pain. For most women, non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit prostaglandin production, such as ibuprofen, can effectively reduce cramping.

17. Prostaglandin inhibitors should be used at the first sign of pain or at the first sign of menstrual flow. Because forceful menstrual cramping may contribute to the development of endometriosis (painful growth of uterine tissue outside of the uterus). Complaints of dysmenorrhea should always be taken seriously, and attempts should be made to reduce its incidence.

18. Amenorrhea Amenorrhea is the absence of a menstrual cycle. -It is considered primary if a woman has never had a menstrual cycle -or secondary if she has had menstrual cycles in the past, but no longer. -Amenorrhea exists naturally before puberty (primary amenorrhea) and after menopause (secondary amenorrhea). -It also occurs during pregnancy, for a few to several weeks after delivery of an infant, and may occur during lactation. -Emotional disturbances and physical stress may also cause amenorrhea. -Endocrine disorders, especially involving the ovaries, pituitary, thyroid, or adrenal glands, can cause amenorrhea, both primary and secondary.

19. Conditions of Disease or Injury Cryptorchidism Is the failure of one or both testicles to descend into the scrotum of a male infant. It is present at birth and is especially common in premature infants. For most infants born with this condition, the testes will descend on their own within the first year of birth. If descent does not occur, the testes will remain at a higher temperature than optimal for spermatogenesis. This may affect sperm quantity and quality, leading to infertility later in life. Male sexual function and secondary sexual characteristics are normal.

20. Clinical Manifestations One or both testes will not be palpable in the scrotum at birth. Diagnostic Tools -Physical examination is used to diagnose the condition. -Ultrasound or other imaging techniques may be used. Complications • Infertility • Increased risk of testicular cancer even after surgical repair. Treatment • Most cases of cryptorchidism will reverse spontaneously within 1 year. If spontaneous descent does not occur, treatment with hCG may stimulate descent. • If hormonal therapy is ineffective, surgery is required by 2 years of age.

21. Varicocele It is an abnormal dilation of a vein in the spermatic cord. A sudden occurrence of a varicocele in an older man may indicate an advanced renal tumor. Clinical Manifestations • May be asymptomatic or associated with a slight feeling of discomfort and testicular heaviness. • Tortuous, dilated veins may be palpable. Diagnostic Tools • Physical examination is used to diagnose the condition. Ultrasound may be used. Complications • Poor blood flow to the testes may cause infertility. Treatment • A support garment for the testicles is worn to relieve discomfort. • To maintain fertility, surgical ligation of the vein may be performed.

22. Hydrocele Is the collection of a plasma filtrate in the scrotum, outside the testes. This filtrate can reduce blood flow to the testes. It may be a congenital or traumatioc. A testicular tumor maybe the cause. May be Idiopathic . Clinical Manifestations A hydrocele may be asymptomatic or associated with palpable or visible swelling and discomfort. Diagnostic Tools Physical examination,ultrasound and visual inspection using a light focused on the testicle may be able to identify fluid. Treatment Identification of the cause and drainage of the fluid.

23. Benign prostatic hyperplasia (BPH) Is the non-cancerous enlargement of the prostate gland. BPH is seen in more than 50% of men older than 60 years of age. BPH may cause compression of the urethra as it passes through the prostate, making urination difficult, reducing force of the flow of the urine stream, or causing dribbling of urine to occur. The cause of BPH is unclear but may be related to an imbalance between estrogen and testosterone in the prostate.

24. Clinical Manifestations • Increased frequency of urination, with delay in initiating urination and a reduction in the force of the urine stream. • As the condition progresses, the bladder may not empty completely, causing dribbling or urine overflow. The time required to void increases. Diagnostic Tools • Diagnosis involves a good history and physical examination coupled with the use of imaging techniques. Biopsy of the prostate may be required to rule out neoplasia.

25. Complications With advanced BPH, urinary tract obstruction may occur as urine is unable to pass through the prostate. Urinary obstruction can lead to urinarytract infections and, if unrelieved, renal failure. Treatment • Mild case is followed in a wait and see‌ manner. • drugs acting by blocking the action of androgens on the prostate. • drugs relaxing the muscles of the bladder and prostate to improve urine flow. Both types of medications may be used concurrently.

26. transurethral incision of the prostate (TUIP). Lasers may be used. • microwave therapy. • If obstruction to urine flow is severe, transurethral prostatectomy (TURP) may be required to remove the enlarged prostate. Complications may include erectile dysfunction and incontinence. • A permanent catheter might be placed in patients unwilling to undergo or unable to tolerate surgery. • Annual digital rectal examinations and screening for prostate-specific antigen (PSA) are encouraged to identify a malignancy that may arise from hyperplastic cells.

27. Inflammatory Disorders of the Male Reproductive Tract Inflammation anywhere between the testes and the urethral opening due to a sexually transmitted disease or a urinary tract infection. Clinical Manifestations • Urethritis may present with pain and burning on urination. A discharge from the penis may be present. • Epididymitis may present with acute scrotal or inguinal pain. Flank pain may be present. The scrotum may be inflamed and tender on the affected side.

28. Orchitis usually presents acutely with a very high fever (104آ°F) and swelling and redness of the testicle and scrotum. The individual appears very ill, and malaise is obvious. • Prostatitis from an ascending urinary tract infection usually presents with painful and frequent urination. Interrupted or slow urine stream and nocturia (urination at night) may be present. Fever and malaise are common. Low back or perineal pain is common, especially when standing. Digital examination reveals a very tender and enlarged prostate.

29. Diagnostic Tools-Blood and urine cultures for the identification of an infectious organism may be required. ComplicationsEpididymitis and orchitis may cause infertility, related to poor testicular blood flow. Treatment • Antibiotic therapy. • Orchitis is treated with bed rest, analgesics for pain, and elevation of the testicles to increase venous drainage. Cold compresses may reduce initial inflammation. If a testicular abscess occurs, surgical removal of the testicle may be necessary.

30. Pelvic Inflammatory Disease (PID) Is the infectious inflammation of any of the organs of the upper genital tract in women, including the uterus, fallopian tubes (salpingitis), or ovaries (oophoritis). The infectious agent is usually bacterial and is often acquired during sexual intercourse. A variety of microbial agents may be implicated, including N. gonorrhoeae, C. trachomatis, and Escherichia coli. In severe cases, the entire peritoneal cavity may be affected. Clinical Manifestations • Although occasionally a woman will be asymptomatic, she usually presents with a high fever and severe bilateral abdominal pain. • Bleeding between periods may occur. • Abdominal pain worsens with intercourse and physical activity.

31. Diagnostic Tools • Palpating or moving the cervix during an internal pelvic examination is very painful. • Purulent discharge at the external os may be apparent on inspection. • Culture of the cervical discharge may indicate the infecting microorganism. • White blood cell count and cell sedimentation rate are usually elevated. • Visualization of the inflamed pelvis by laparoscopy, the insertion of a fiberoptic probe, can be used to confirm the diagnosis of PID.

32. Complications • PID may lead to scarring and adhesions of the uterus or fallopian tubes, predisposing a woman to infertility. • Pelvic adhesions and scarring increase the risk of a subsequent ectopic pregnancy. In an ectopic pregnancy, the embryo implants and grows at a site other than the uterus, usually the fallopian tube. Rupture of the fallopian tube may occur, leading to internal hemorrhage and maternal death. • Approximately 5% to 10% of women with PID die, usually from septic shock.

33. Treatment • Antibiotic therapy. • Avoidance of sexual intercourse until the inflammation has subsided. • Education on the use of barrier methods of contraception (condom, diaphragm with foam or jelly) to prevent future occurrences of sexually transmitted disease is important. • Birth control pills may reduce PID by increasing the production of cervical mucus, but do not replace the need for a condom. • The sexual partner(s) of an affected woman should be evaluated for infection and, if necessary, treated with antibiotics. • Appendicitis must be ruled out as the cause of abdominal pain.

34. Endometriosis Endometriosis is the presence of uterine endometrial cells outside the uterus, anywhere in the pelvic or abdominal region. The endometrial cells respond to estrogen and progesterone with proliferation, secretion, and bleeding during the menstrual cycle. This can cause inflammation and severe pain. The inflammation may lead to scarring of pelvic or abdominal organs and infertility. Clinical Manifestations • Menstrual cramping and pain, ranging from mild to severe, before and/or during menstruation is the most common symptom of endometriosis. • Changes in bowel movements, either diarrhea or constipation, may occur around the time of menstruation. • Pain with intercourse (dyspareunia) or during defecation (if rectal tissue is involved). The pain is usually worse during menstruation, but in severe cases pain may be constant.

35. Diagnostic Tools Visualization of the peritoneal cavity using laparoscopic techniques . Complications -Infertility is a common (30% to 40%) complication of endometriosis. Endometriosis may cause infertility by causing scarring and obstruction of the fallopian tubes or by initiating a maintained state of inflammation. Hormonal disturbances may occur. Emotional distress, family and marital problems, .especially if infertility is a concern

36. Cancer of the Male Reproductive Tract May develop in the penis, testes, or prostate. Penile Cancer Primary cancer of the penis is rare in the United States. It usually occurs in non-circumcised men, possibly related to accumulation of thick secretions (smegma) under the foreskin Secondary penile cancer may occur from metastasis of bladder, rectal, or prostate cancer. Testicular Cancer Testicular cancer is rare, mostly occurring in young men between the ages of 15 and 35. The cause of testicular cancer is unknown, but occurs more frequently in men with a history of cryptorchidism. Trauma and prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) may increase risk.

37. Prostate Cancer Prostate cancer is the number one cancer among American males and the second leading cause of death due to cancer in that population (the first is lung cancer). Prostate cancer is usually diagnosed in men older than 65 years of age. Clinical Manifestations • Penile cancer is characterized by an ulcerative lesion on the shaft of the penis that may or may not be painful. • Testicular cancer is characterized by the development of a mass in the testis, which may become painful as it grows. Testicular heaviness or aching may occur. Gynecomastia may develop. • Prostate cancer may be asymptomatic or associated with increased frequency and urgency of urination, and a decrease in the force of the urine stream. Blood may be passed in the ejaculate, and in advanced disease, back pain may be present.

38. Diagnostic Tools • Biopsy of cells of the penis can diagnose and stage penile cancer. • Transillumination of the testes, ultrasound, and MRI may identify a testicular mass and support clinical findings of a testicular cancer. • A digital rectal examination may reveal a fixed, firm mass in the prostate, suggestive of a tumor. The mass is often painless with irregular borders and results in asymmetry of the prostate gland. Ultrasound may be used to pinpoint the location of a prostate tumor. A biopsy of prostate cells taken via a transurethral resection can confirm the diagnosis of prostate cancer. • Prostate-specific antigen (PSA), can be used to identify the presence of even early-stage prostate cancer. • Measurement of PSA levels coupled with findings from a digital exam offer the most sensitive screening results.

39. Complications • Untreated, progressive penile cancer has an extremely high mortality rate (about 90%). • Testicular cancer may metastasize to the lungs, lymph nodes, or central nervous system. • Survival with prostate cancer depends on the stage at diagnosis. Most men diagnosed with stage D cancer die within 3 to 5 years. • Erectile dysfunction and incontinence may develop as a result of any of the male reproductive cancers or may develop following treatment of the cancers.

40. Cancer of the Female Reproductive Tract May develop in the vagina, uterus, or ovaries. • Vaginal Cancer Vaginal cancer usually occurring in women older than 60 years of age. The vaginal squamous cells are most often involved. Frequently, the cancer is a secondary metastasis. • Uterine Cancer includes: -Cervical cancer is often a result of a sexually transmitted disease of the cervix caused by certain strains of the human papillomavirus (HPV). Cervical cancer is most common in women who have had multiple sexual partners. The premalignant changes, called dysplasia, can be identified and staged during cytologic studies of a cervical smear (the Papanicolaou smear, or Pap smear). -Uterine endometrial cancer is the most common female reproductive cancer and is usually an adenocarcinoma (from the epithelial cells). Endometrial cancer is related to lifetime exposure to estrogen and typically presents in postmenopausal women.

41. Ovarian Cancer Although relatively rare, ovarian cancer causes death more often than any other female reproductive cancer. Clinical Manifestations • Vaginal cancer may be asymptomatic or associated with bleeding, discharge, or pain. • Cervical cancer may be asymptomatic or associated with bleeding after intercourse or spotting between menstrual periods. A vaginal discharge with odor may be present. • Endometrial cancer may be asymptomatic or associated with abnormal bleeding. • Ovarian cancer is usually asymptomatic until the disease is advanced. Late symptoms include abdominal swelling and pain. Gastrointestinal obstruction may cause vomiting, constipation, or small-volume diarrhea.

42. Diagnostic Tools • The Pap smear can identify cervical and endometrial cancer. • Direct cytologic sampling of the vagina and endometrium can diagnose vaginal and endometrial cancer. • Ovarian cancer can be identified by use of MRI or vaginal ultrasound. The ovaries may be palpable. Surgery is required to stage the disease and identify metastases. Increased level of an ovarian tumor cell antigen, CA125, in a symptomatic woman or a woman with a family history of ovarian or breast cancer can be an early indication of disease.

43. Complications • Death may occur with any of the reproductive cancers. Survival rates are highest (75 to 95%) with endometrial cancer and lowest (25 to 30%) with ovarian cancer. Early detection can improve survival rate significantly, especially for cervical cancer, which has a survival rate near 100% if identified while still in situ (before it has spread). Treatment • Surgery, with or without chemotherapy. Laser surgery or cryosurgery (freezing) may be used for vaginal or cervical cancers. Improved chemotherapy has increased survival rate for all reproductive cancers, including ovarian cancer. • Prophylactic bilateral salpingo-oophorectomy, the removal of both ovaries and fallopian tubes, may be performed on women at high risk of ovarian cancer who choose this option.

44. Breast Cancer • Breast cancer may be discovered while in situ (localized), or it may be discovered as a malignant (spreading) neoplasm. Breast cancer is usually an adenocarcinoma found in the milk ducts. Risk Factors for Breast Cancer • - A history of the disease in one or more first-degree relatives (sisters or mother). • - Lifetime estrogen exposure. Women who experience early menarche and late menopause are at increased risk.

45. - Lack of or delayed childbearing • estrogen replacement therapy. • - A high-fat diet and, in some studies, alcohol consumption . • - Hormone replacement therapy (HRT) in postmenopausal women . • N.B.,Protection against breast cancer is possible by consumption of a diet rich in fruits and vegetables, regular exercise, and weight control.

46. Clinical Manifestations • A painless lump or mass in the breast. Most cancers occur in the upper outer quadrant of the breast (50%) or in the center of the breast (20%). The lump is usually unilateral and fixed (non-mobile), with irregular borders. • Retraction of the nipple, nipple discharge, or puckering of the breast tissue may signal an underlying tumor. • Lymph node swelling, either axillary or clavicular, may indicate metastasis.

47. Diagnostic Tools • Breast self-examination (BSE) performed on a regular (monthly) basis. BSE should be performed by all women older than 20 years. • Mammography, the increased use of mammography has contributed to the fall in death rate due to breast cancer. Annual or biannual mammography is recommended for all women older than 40 years of age and for younger women with a family history of the disease or other risk factors. • Biopsy of a suspected lump will confirm the diagnosis. Determination of tumor size, tumor characteristics, and examination of surrounding lymph nodes allow for staging and histologic classification of the tumor. Staging is from I to IV and is important in determining treatment and in estimating prognosis

48. Complications Widespread metastases may occur. Sites of metastasis include the brain, lungs, bone, liver, and ovaries. Treatment • Surgery, including mastectomy or lumpectomy. Nodal involvement indicates metastasis of the tumor and requires more aggressive post-surgical interventions. • Adding radiotherapy or chemotherapy in conjunction with surgery improves survival and reduces the likelihood of recurrence. These therapies are based on the presence or absence of metastasis.

49. Sexually Transmitted Infection (STI) may develop in anyone having sexual contact with multiple partners. Microorganisms capable of causing an STI include the bacteria Neisseriagonorrhoeae, responsible for causing gonorrhea, and Treponemapallidum, responsible for causing syphilis. The herpes simplex virus, human papillomavirus (HPV), hepatitis B virus, and human immunodeficiency virus (HIV) are also sexually transmitted. Trichomonasvaginalis is a protozoan responsible for causing trichomoniasis. An STI may be passed via semen or vaginal secretions or by skin-to-skin contact.

50. Clinical Manifestations • Gonorrhea may be asymptomatic or may present with purulent discharge from the urethra or vagina and burning on urination. Some individuals, including infants born to infected mothers, may develop conjunctivitis or pharyngitis. • Primary syphilis is characterized by the presence of a painless genital ulcer (chancre) that spontaneously regresses. Secondary syphilis develops weeks to months later and is characterized by a temporary skin rash, typically located on the palms of the hands and the soles of the feet. Tertiary syphilis may develop decades after the initial infection and is characterized by sensory loss, muscle weakness, and heart defects. • Trichomoniasis may be asymptomatic or may present with greenish discharge and itching. Pain with intercourse is common. Men are seldom symptomatic.