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Alterations in Sexual Maturation P816-819 Process of sexual maturation (puberty) is marked by development of 2ndary sexual characteristics, rapid growth and the ability to reproduce. Delayed or early puberty involves a disrupted onset of sex hormone production by the gonads. o Delayed puberty Thelarche (breast development) should begin at 13 for girls, boys 1st sign around 14 years old is enlargement of testes/thinning of scrotal skin. Considered delayed if NO signs of puberty by 13 in girls and 14 in boys. 95% of cases attributed to physiologic delay (hormonal levels are normal & HPG (hypotha-pituit-gonad) is intact but maturation is slow) tends to be familial and more common in boys than girls other causes may be related to consequences of any chronic condition that delays bone aging (lung disease, renal failure, cystic fibrosis) 5% of cases caused by disruption of the HPG axis o Precocious puberty (early onset) Sexual maturation before age 6 in black girls or 7 in white girls, and before age 9 in boys Rare, 1/10,000 girls and less than 1/50,000 boys (much more common in girls) Causes are either: central (GnRH dependent: HPG axis working normally but prematurely) or peripheral (GnRH independent: sex hormones produced by some mechanism other than stimulation by gonadotropins) o this may include sex-steroid releasing tumor, testotoxicosis, hormonal contraceptives Forms are: Complete: onset/progression of all pubertal features (thelarche, pubarche & menarch) Partial/incomplete: partial development of appropriate 2ndary characteristics alone or in combination (example: girl undergos thelarch or pubarche but rarely premature menarche) Mixed/heterosexual: virilization of a girl or feminization of a boy causes child to develop 2ndary characteristics of opposite sex Hormonal/Menstrual Alterations of Female Reproductive System (FRS) P819-828 Primary Dysmenorrhea o What is it? Painful menstruation associated with release of prostaglandins in ovulatory cycles (NOT associated with pelvic disease) Severity related to duration/amount of menstrual flow, between 50-90% of women aged 15-25 years old are affected Secondary dysmenorrhea is related to pelvic pathology, manifests in later reproductive years & may occur any time in menstrual cycle o Pathologic mechanism? Excessive endometrial prostaglandin production (enhanced by progesterone) o Symptoms? Pelvic pain associated with onset of menses, backache, anorexia, vomiting, diarrhea, headache o Treatment? Hormonal contraceptive, non-steroidal/non-inflammatory meds, regular exercise, stress reduction, heat, massage Amenorrhea o What is it? Lack of menstruation Primary = failure of menarche/absence of menstruation by age 14 w/out development of 2ndary sex characteristics of by age 16 regardless of presence of 2ndary characteristic Differs from delayed puberty in that most cases of delayed puberty require only reassurance o Mechanism? Compartment IV disorders (CNS disorders, in particular the hypothalamus) Hypoth-pituit-ovarian axis is dysfunctional. Hypoth doesn’t secrete GnRH, which doesn’t stimulate pituitary to release LH/FSH, therefore the ovary doesn’t receive hormonal signals that would initiate menstruation. b/c ovarian hormones are absent, estrogen-dependent sex characteristics don’t develop Compartment III disorders (anterior pituitary problems, including tumors) Tumors, lesions, trauma, hydrocephalua, etc. can interfere with hypothal-pituit unit, which interrupts the secretion of GnRH/LH/FSH. These lesions develop between the onset & conclusion o puberty, so skeletal growth & 2ndary characteristics may develop, but sexual maturation is interrupted before menarche can begin Compartment II disorders (involve the ovary) Includes genetic problems such as gonadal dysgenesis (Turner syndrome), androgen insensitivity syndrome (AIS), poly-X o Turner syndrome: ovaries lack gametes/ovarian failure is complete, so follicular development & estrogen secretion can’t occur This leads to lack of 2ndary sex characteristics & menstruation o AIS: person is genetically male but has female morphology o Poly-x: “superfemale syndrome” XXX (extra X chromosome in female) Compartment I disorders (anatomic defects of the outflow tract associated with primary amenorrhea) Includes congenital absence of a vagina & uterus, congenital uterine hypolplasia (infantile uterus) Skeletal growth & 2ndary sex characteristics occur but no menstruation and uterus doesn’t respond during puberty o Symptoms? Pregnancy (if you don’t have menses, you may be pregnant) o Treatment? Correct underlying problems, hormone replacement therapy, surgical alteration of genitalia Secondary Amenorrhea o What is it? The absence of menstruation for a time equivalent to 2+ cycles or 6 months in women who have previously menstruated May be associated with dramatic weight loss, disease, and is normal during early adolescence, pregnancy & lactation Most common causes (after pregnancy) are thyroid disorders, hyperpolactinemia, HPO interruption 2ndary to excessive exercise, stress, weight loss and polycystic ovary syndrome o Mechanism? See Figure 23-2 on P821 If there is normal ovarian hormone secretion, causes could be: Pregnancy, uterine dysfunction caused by hysterectomy or endometrial ablation/adhesions (destroys lining of uterus) If there is decreased ovarian hormone secretion w/ high gonadotropin levels, causes could be: Menopause, ovarian failure caused by gonadal dysgenesis, resistance to gonadotropins, autoimmune disease, chemotherapy, environmental toxins, and premature ovarian failure If there is decreased ovarian hormone secretion w/ low gonadotropin levels, causes could be: Secondary ovarian failure caused by hyperprolactinemia, hypoth-piuit disorders, function hypothal-anovulation caused by starvation or psychogenic problems If there is an increase in ovarian hormone secretion with low/normal gonadotropin levels causes could be: Excessive testosterone/progesterone, ovarian tumor, adrenal tumors or congenital adrenal hyperplasia o Symptoms? Absence of menses, infertility, vaginal atrophy, acne, osteopenia, and abnormal hairiness o Treatment? Oral, vaginal or injectable hormone replacement therapy, surgical removal of tumors Abnormal/Dysfunctional Uterine Bleeding (DUB) o What is it? Heavy/irregular bleeding in the absence of organic disease o Mechanism? Most are attributed to: anovulatory cycles: most prevalent, associated with PCOS, immaturity of the HPO axis, obesity, hyper/hypothyroidism, and estrogen-secreting ovarian neoplasms corpus luteum defects or atrophic endometrium: due to progesterone deficiency or estrogen excess o Symptoms? Unpredictable/variable bleeding in terms of amount/duration, excessive bleeding can cause anemia so fatigue, shortness of breath and iron deficiency are symptoms o Treatment? Hormone therapy, various meds consistent with cause of bleeding, hysterectomy, ablation or IUD (by decreasing endometrial proliferation, IUD helps control blood flow) Polycystic Ovary Syndrome (PCOS) o What is it? Characterized by excessive production of androgen (causes premature follicular failure & persistent anovulation) & estrogen Has at least 2 of the following symptoms: oligo-ovulation or anovulation, elevated levels of androgens, clinical signs of hyperandrogenism and polycystic ovaries Polycystic ovaries don’t have to be present to diagnose PCOS and alternatively their presence alone doesn’t indicated PCOS o Mechanism? Unknown cause, genetic factor is suspected High levels of LH increase androgens from adrenal gland and testosterone from the ovaries. Androgens convert to estrogen. High levels of estrogen continue to raise LH but lower FSH (so follicular growth is stimulated but never fully matures). Follicles are “left” in ovary and eventually can turn into cysts. o Symptoms? Change over time with metabolic syndrome becoming more prominent with age. May be associated with Cushing syndrome, acrogmegaly, premature ovarian failure, simply obesity, congenital adrenal hyperoplasia, thyroid disease, or ovarian tumors Other symptoms include dysfunctional bleeding, hirsutism (excessive hair in inappropriate places), acne and infertility o Treatment? Difficult to diagnose since so many symptoms/complications can be involved Oral contraceptives (progesterone therapy to over-rule high estrogen levels), antiandrogens and fertility agents used Medicine that decreases insulin levels (which seems to play a role associated with high androgen levels) Lifestyle changes such as diet and exercise Premenstrual Disorders (PMS & PMDD) o What is it? Cyclic recurrence (in luteal phase) of distressing physical, psychological or behavioral changes that impair interpersonal relationships or interfere with usual activities o Mechanism? It may be the result of abnormal tissue response to the normal changes of the menstrual cycle, perhaps due to fluctuating estrogen/progesterone levels. Neurotransmitters (GABA, serotonin, and noradrenaline) may have mediating roles Appears to be genetic o Symptoms? Frequency/severity is most important indicator since over 300 physical, emotional, & behavioral symptoms have been attributed to this one disorder Depression, anger, irritability, fatigue are most prominent complaints o Treatment? Eliminate contributing factors, treat coexisting disorders, offer resources for emotional support, counseling, meditation, exercise, good sleep, dietary changes, decreasing caffeine/alcohol & increasing water, anti-depressents, vitamin supplements, oral contraceptives Infections/Inflammation of FRS P828-833 Results from endogenous (includes infections from microorganisms that are already present in the vagina, bowel or vulva) or exogenous (usually STDs) causes Pelvic Inflammatory Disease (PID) o What is it? Acute inflammatory process caused by infection. May involve any organ (or combination) of the upper genital tract (uterus, fallopian tubes (salpingitis), & ovaries (oophoritis)) and in its most severe form, the entire peritoneal cavity o Mechanism? Usually due to a failure of defense mechanisms that usually protect against PID, most often a polymicrobial infection (including facultative and anaerobic organisms & genital tract mycoplasmas) Occurs when pathogenic microbes ascend from infected cervix to uterus and further, some organisms change endothelium making it more susceptible to infection The more instances one has to PID, the higher their chances of infertility o Symptoms? Sudden, severe abdominal pain with fever OR no symptoms at all, may have difficulty urinating or irregular bleeding 15-25% of women after one episode develop long-term sequelae (a condition that is consequence of a previous disease/injury): infertility, ectopic pregnancy, chronic pelvic pain, dyspareunia (painful intercourse), pelvic adhesions, perihepatitis (inflamm of serous/peritoneal coating of liver), tuboovarian abscess o Treatment? Bed rest, avoidance of intercourse, antibiotic therapy Vaginitis o What is it? An infection of the vagina usually caused by sexually transmitted pathogens & Candida albicans o Mechanism? Related to loss of local defense mechanisms (skin integrity, immune reaction, and vaginal pH) Can be caused by douching, spermicides, hygiene sprays/deodorant sprays, tampons, diabetes/pregnancy, antibodies o Symptoms? Marked change in color of discharge or discharge becomes copious (overabundant amount), malodorous (bad smell) or irritating o Treatment? Maintaining an acidic environment, relieving symptoms, administer antimicrobial/antifungal meds Cervicitis o What is it/Mechanism? Nonspecific term to describe inflamm of the cervix prior to the identification of pathogens Specific cervicitis includes: Mucopurulent cervicitis (MPC) is caused by 1+ more sexually transmitted pathogens o Cervix becomes red/edematous, mucus drains from external cervical os (external orifice of the uterus) o Symptoms & Treatment? pelvic pain, bleeding or dysuria, many times there is bleeding during intercourse or Pap smears antibiotic therapy Vulvovestibulitis (vulvitis) o What is it/Mechanism? Inflammation of vulva or vestibule of genitalia or both May represent several disorders w/out identifiable cause, fairly common May be caused by: contact dermatitis (soaps, detergents, lotions, sprays, shaving, tampons, tight fitting clothes) abnormalities in vestibular mucosa, pelvic floor musculature, or CNS pain regulatory pathways an autoimmune reaction vaginal infections that spread to the labia, where they cause inflamm & edema o Symptoms & Treatment? Behavioral treatment or vestibulectomy (removing the vulvar vestibule) Other paproaches with little research to support them include hydrocortisone cream, applying a water barrier during a period of healing, lidocain application Bartholinitis o What is it/Mechanism? Inflammation of 1 or both of the ducts that lead from the introitus (vaginal opening) to the Bartholin glands Caused by microorganisms that infect the lower female reproductive tract (like streptococci, staphylococci), may be preceded by an infection (such as cervicitis, vaginitis or urethritis) This infection causes inflammatory changes that narrow the distal portion of the duct, leading to obstruction/stasis (slow/stopping of bodily fluid) of glandular secretions This obstruction (or cyst) redeens and is painful, pus may be visible at opening of duct o Symptoms & Treatment? Fever, malaise (symptoms of infection), most are asymptomatic and require no treatment, antibiotics may be given Pelvic Organ Prolapse (POP) P833-836 Anatomy overview: o The bladder, urethra and rectum are supported by the endopelvic fascia & the perineal muscles (particularly the levator ani group). This muscular/fascial tissue loses tone & strength with aging (or pregnancy) & may fail to maintain the pelvic organs in the proper position. Progressive descent of the pelvic support structures may cause pelvic floor disorders and pelvic organ prolapse. Details: o Nearly 24% of women experience at least 1 POP o Caused by trauma (childbirth or pelvic surgery or damage to pelvic innervation), genetic factors play a role, it is progressive and related to the inherent strength/weakness of the woman’s musculofascial tissue o Black & Asian women have lowest risk, Hispanic have highest risk o Evaluation is graded on a scale of 0 (normal position) to 4 (maximal possible decent of uterus, meaning it is literally protruding out of the vagina, past the hymen, etc.) Uterine Prolapse: o What is it? Decent of the cervix or entire uterus into vaginal canal (most severe case the uterus protrudes from the introitus) o Symptoms/Treatment? Besides seeing a uterus coming out of your vagina, more subtle symptoms might be a feeling of fullness or heaviness Kegel exercises help, estrogen therapy, maintaining healthy body mass index, preventing constipation and treating chronic cough may help prevent. May have a pessary inserted, which is a removable mechanical device that holds the uterus in position Surgical repair is last resort Cystocele o What is it? Descent of a portion of the posterior bladder wall & trigone (a smooth triangular area on the inner surface of the bladder) into the vaginal canal (usually caused by childbirth) In severe cases the bladder wall protrudes outside the introitus NOTE: it does NOT cause urinary incontinence o Symptoms/Treatment? Woman may explain discomfort as if she’s “sitting on a ball”, slight vaginal pressure Kegel exercises help, estrogen therapy, pessary inserted, surgical repair is last resort Urethrocele o What is it? Sagging of the urethra, commonly associated with cystocele Caused by the shearing effect of the fetal head on the urethra during childbirth Cystourethrocele o What is it? herniation of the neck of the female bladder and associated urethra into the vagina Occurs in nulliparous women (women who have not experienced childbirth), caused by congenital weakness/relaxation of the musculature of pelvic floor Rectocele o What is it? Bulging of the rectum & posterior vaginal wall into the vaginal canal Damage may occur during childbirth but symptoms don’t occur until years after menopause Familial/genetic & bowel habits contribute to disorder o Symptoms/Treatment? Usually asymptomatic but severe cases cause vaginal pressur,e rectal fullness and incomplete bowel evacuation Treatment focuses on preventing constipation, if needed use of pessary Enterocele o What is it? Herniation of rectouterine pouch into the rectovaginal septum (between rectum & posterior vaginal wall). IN other words, the small bowel descends into the lower pelvic cavity & pushes at the top part of the vagina, creating a bulge Can be congenital or acquired (if acquired usually associated with other pelvic prolapse disorders) o Treatment is surgical Benign Growths & Proliferative Conditions P846-848 Benign Ovarian Cysts o What is it/Mechanism? Produced when a follicle (s) are stimulated but no dominant follicle develops/completes the maturity process o Details: Occur at any time but more common during reproductive years, chances increase when hormonal imbalances are rampant (puberty & menopause) Quite common o 2 common types of functional cysts (caused by variations of normal physciologic events) follicular cyst: What is it? o a transient condition in which the dominant follicle fails to rupture or 1+ of the non-dominant follicles fail to regress Mechanism? o reason not well understand. May be that hypothalamus doesn’t receive/send a message strong enough to increase FSH (which is needed to develop/mature a dominant follicle). When FSH is low, estradiol doesn’t increase enough to stimulate LH Symptoms & Treatment? o include bloating, swollen/tender breasts and heavy/irregular menses o usually the cyst is absorbed/regresses on its own corpus luteum cyst What is it? o Develops when an imbalance in low LH & progesterone levels causes an inadequate development of the corpus luteum o Less common than follicular cyst but can cause more symptoms/pain Symptoms & Treatment? o Dull pelvic pain, delayed menstruation, irregular bleeding, rupture of cyst can occur & results in massive bleeding with excruciating pain (immediate surgery required) o Usually they regress in non pregnant women, oral contraceptives can be used to prevent future cysts o Dermoid cyst: What is it? Ovarian teratomas (a tumor derived from more than one embryonic layer ) that contain elements of all three germ layers (these are common ovarian neoplasms (a new growth of tissue serving no physiological function)) These are the cysts that can contain teeth, hair, bone, etc. They have malignant potential so should be removed (usually they’re asymptomatic) Endometrial Polyp o What is it/Mechanism? Benign mass of endometrial tissue on the lining of the uterus, covered by a surface epithelium and contains glands, stoma and blood vessels Related to estrogen stimulation, usually develops in women 40-50 years old (although it can occur at all ages) o Symptoms & Treatment? Irregular bleeding, excessive heavy periods, bleeding after menopause Known to spontaneously resolve but polypectomy can be performed through hysteroscopy (endoscope exam of cervic/uterus) for symptomatic women or those with malignant risk Leiomyomas (myomas or uterine fibroids) o What is it/Mechanism? Benign smooth muscle tumors in the myometrium (muscle layer) of the uterus Most common benign tumors of the uterus (affects 70-80% of women), slow growing, black and Asian women are at much higher risk than white women Cause unknown but appears to be related to estrogen, progesterone, growth factors, angiogenesis (the formation and differentiation of blood vessels) & apoptosis (genetically determined cell self-destruction, “cell suicide”) o Symptoms & Treatment? Most remain small & asymptomatic May have abnormal bleeding, pain and pressure, attributed to infertility, growing pressure by the tumor may disrupt nearby structures (bladder for instance) Try to shrink the tumor with contraceptives, GnRH agonists, antidepressants. Myomectomy remains the standard cure Adenomyosis o What is it/Mechanism? Endometrial cells from uterus migrate into the myometrial layer Estrogen/progesterone likely play a role, different from endometriosis in that it doesn’t respond to cyclic hormone changes o Symptoms & Treatment? Irregular bleeding, uterine enlargement, uterine tenderness during menstruation Treatment includes non steroidal inflammatory drugs, levonorgestrelcontaining IUDS, maybe surgical treatment if serious Endometriosis o What is it/Mechanism? Presence of functioning endometrial tissue outside the uterus Cause unknown but suspected reasons include: May be caused by menstrual fluids that move through the fallopian tubes & empty into the pelvic cavity (retrograde menstruation). Now likely it since most women experience this but not all women have endometriosis. Another theory is that women with this condition have impaired cellular/humoral immunity (T cell and natural killer cell activity has been found to be depressed). At the same time, macrophages are stimulating endometrial cell proliferation outside the uterus. An autoimmune response is also suspected. Or perhaps endometrial cells spread through lymphatic or vascular systems and somehow stimulate epithelial cells covering reproductive organs to develop into endometrial cells. Genetic predisposition. NOTE: Important to understand that this tissue responds to hormonal changes of menstrual cycle. So when uterus sheds lining, the ectopic endometrium also sheds. This bleeding causes inflammation and pain. It can lead to fibrosis, scarring and adhesions. o Symptoms/Treatment? Infertility, pelvic pain, irregular menses, pain on defecation (dyschezia), pain on intercourse (dyspareunia), constipation Treatment aimed at preventing/decreasing progesterone, alleviating pain and restoring fertility Cancer P841-848 Malignant tumors of FRS are common; endometrial carcinoma (5.8% of all cancers in women), ovarian tumors (3.1% of all cancers) and cervical cancers (1.6% of all cancers). Malignant neoplasms account for 13.3% diagnosed cancers and 11.3% cancer deaths in women in the US. Cervical Cancer o What is it? Most common cancer in women worldwide, higher risk in black women Caused by HPV infection, infection of strands 16 & 18 leads to precancerous dysplasia of the cervix, which leads to cervical cancer Precancerous dysplasia (cervical intraepithelial carcinoma, CIN) or cervical carcinoma in situ (CIS) occurs more often in younger women. About 50% of young women acquire HPV and the immune system can usually flush it out. o Mechanism? Slowly progressive, staged according to histology (changes in cells indicated what stage/severity the cancer is currently at). Stages from least to most invasive: Cervical intraepithelial neoplasia (dysplasia) o Replacement of some epithelial cells by atypical, neoplastic cells. Stages within this stage are shown in Table 23-6 on P842 o Most abnormalities here will regress on their own without further progression Cervical carcinoma in situ o In the “transformation zone” columnar epithelium is replaced by squamous epithelium in a process known as metaplasia. Generally this stage is a precursor of invasive carcinoma of the cervix (Table 23-6 on P842) Invasive carcinoma o Direct invasion into adjacent tissues/metastasis through the lymphatics (Table 23-6 on P842) Cause not really known but like other cancers, cervical cancer requires the accumulation of genetic alterations for carcinogenesis to occur o Symptoms & Treatment? Asymptomatic so regular Pap test or HPV screening is recommended, if symptoms exist may include vaginal bleeding or abnormal discharge, foul odor may be present Biopsy performed to confirm progression, laser treatment may be used for CIS level, burn off cancer cells using LEEP, conization (remove cone-shaped section of tissue that includes cancer). For invasive carcinoma, surgical intervention, radiation therapy. Cure rate is very high if caught early. Vaginal Cancer o What is it/Mechanism? Rare (1-2% of gynecologic cancers). Most are squamous cell-type cancers (remaining are adenocarcinomas, sarcomas & melanomas) Similar etiology as cervical cancer: both start a intraepithelial lesions, occurs in sexually active women and are associated with HPV (prior carcinoma of cervix increases risk of vaginal cancer). In utero exposure to nonsteroidal estrogens also a risk factor. Have same stages as cervical cancer (dysplasia, carcinoma in situ and invasive) & are staged based on extension into local tissues/metastasis to distant organs o Symptoms & Treatment? Asymptomatic generally, vaginal bleeding my occur & in advanced stages rectal/bladder symptoms, pain/leg edema can occur Excised with upper vaginectomy, laser ablation or LEEP, laser surgery, or surgery with hysterectomy, radiation & chemo Chances of recovery go down the worse the stage becomes Vulvar Cancer o What is it/Mechanism? Responsible for 5% of all gynecologic cancers, majority are squamous cell carcinomas with the remaining as melanoma, Bartholin gland carcinoma, sarcoma and adenosquamous carcinoma History of HPV, chronic vulvar irritation, squamous dysplasia of the vagina/cervix, smoking and coffee use are all risk factors o Symptoms & Treatment? May have a hard ulcerated area of the vulva, large cauliflower lesions or lesions similar to those of chronic dermatitis Ablative/excisional surgery, sometimes radiation Endometrial Cancer o What is it/Mechanism? Most common form of pelvic region cancer (13%), arises within the glandular epithelium of the uterine lining Incidence rate higher in whites but mortality is higher in blacks Primary risk factor is unopposed estrogen exposure with resultant hyperplasia (estrogen therapy, early menarche, late menopause, never having kids, failure to ovulate, obesity) o Symptoms/Treatment? Abnormal bleeding is usually a sign, pain/weight loss are signs of late disease progression Pregnancy & the use of combined hormonal contraceptives containing estrogen/progestin have protecting effects, changing diet, exercise, surgical excision may be necessary if serious Uterine sarcomas o What is it? Rare neoplasms that arise from myometrial smooth muscle of uterus, endometrial stroma or connective tissue elements Chronic excess estrogen exposure, tamoxifen and black race are risk factors o Symptoms/Treatment? Abnormal bleeding, awareness of a mass, pelvic pressure/pain, vaginal discharge, GI problems Total hysterectomy followed by radiation therapy Ovarian Cancer o What is it? Accounts for 5% of all female cancer deaths, 5th most frequent cancer in women Associated with early menarche, late menopause, nulliparity, and the use of fertility drugs, also prior pelvic radiation plays a factor Cause is unknown, suggested that repetitive ovulatory tissue repair may produce mutations o Mechanism? Most malignancies are epithelial ovarian neoplasms (develop from the surface epithelium of the ovary or that which line cysts immediately beneath the ovarian surface) 90% of all ovarian malignancies are classified as ovarian adenocarcinomas (malignant form of epithelial ovarian neoplasms) Germ-cell tumors are derived from the primitive germ cells of the embryonic gonad and may be malignant of benign (almost always occur in children/adolescents) o Symptoms & Treatment? Range of symptoms depending on type of tumor/level of growth, but may include pain and abdominal swelling, vomiting, alterations in bowel habits, abnormal vaginal bleeding Treatment may include surgery, radiation therapy, chemotherapy Sexual Dysfunction in Females P848-849 Organic & psychosocial disorders are implicated. Chronic illness can affect sexual functioning (see Table 23-9 on P849) Some examples: o Disorders of desire (inhibited sexual desire, decreased libido): may be biologic manifestation of depression, alcohol/substance abuse, prolactin secreting pituitary turmos, or testoerone deficiency o Vaginismus: involuntary muscle spasm in response to attempted penetration, causes include prior sexual trauma/fear of sex, may be a physical problem too (such as vulvovestibulitis) o Anorgasms (orgasmic dysfunction): inability to achieve orgasm, may be caused by diabetes, alcoholism, neuralgic disturbances, certain meds, hormonal deficiencies & pelvic disorders (infections, trauma and surgical scarring) o Rapid orgasm: rare, once orgasm occurs there’s little interest in further sexual activity (aka, male sex syndrome… j/k) o Dyspareunia (painful intercourse): psychosocial (history of sexual trauma, depression, relationship factors play a role) or organic (inadequate lubrication, drugs with drying effect, disorders such as diabetes, vaginal infections, estrogen deficiency, infections around vulva area) causes Impaired Fertility P849-850 Affects 15% of all couples, defined as the inability to conceive after 1 year of unprotected intercourse Male factors include diminished quality/production of sperm, female factors associated with malfunctions with the fallopian tubes, ovaries or reproductive hormones Disorders of the Male Reproductive System P850-869 Disorders of the Urethra o Urethritis: inflammation of the urethra w/out bladder infection, usually cased be ST (sexually transmitted) microorg Man may feel tingling, itching, burn during urination, may be a discharge, treated with antibiotics o Urethral Stricture: fibrotic narrowing of the urethra caused by scarring, usually due to trauma/infections from long0term use of indwelling urinary catheters Man may experience diminished force/caliber of urinary stream, urinary frequency/discomfort. Treatment is surgical. Disorders of the Penis o Phimosis/Paraphimosis Foreskin is too tight to be move easily over the glans penis Phimosis: foreskin can’t be retracted back over the glans Paraphimosis: foreskin is retracted & can’t be moved forward to cover the glans Can occur at any age, usually due to poor hygiene and chronic infection Edema, erythema and tenderness along with discharge my be signs (and the fact that your foreskin is stuck….. hmm….). Paraphimosis can constrict the penis so it’s important to get that fixed asap. Surgery is usually the preferred method. o Peyronie Disease Fibrotic condition resulting in varying degrees of curvature and sexual dysfunction, “bent nail syndrome” Can cause painful erection/intercourse, poor erection Spontaneous resolution occurs in ½ the cases o Priapism Uncommon, prolonged penile erection, usually painful & not associated with arousal Idiopathic in 60% cases, 40% are associated with spinal cord trauma, sickle cell, leukemia, pelvic tumors or infections It is an emergency since edema and fibrosis develops quickly leading to impotence. Needle aspiration of blood, surgical treatment or iced saline enemas are some treatments o Balanitis Inflammation of glans penis and occurs in conjunction (usually) with posthitis (inflammation of the prepuce) Associated with poor hygiene, poorly controlled diabetes mellitus and candidiasis o Penile cancer Rare in the US, twice as common in black men, usually affects men older than 50, risk factors include PV, smoking and psoriasis; men circumcised at birth have less than ½ the chance of getting it than uncircumcised Mostly squamous cell carcinoma, which beings as small, fat, ulcerative/papillary lesions on the glans or foreskin that grow to involve the entire shaft May involve circumcision (in extreme situations, the removal of the penis altogether). Newer techniques involve surgical steps, radiation or chemo Disorders of the scrotum/tests/epididymis o Scrotum May have a painful/painless mass that can be serious (cancer or torsion) or benign (hydrocele or cyst). May require surgical intervention or careful observation Varicocele: abnormal dilation of a vein within spermatic cord/described as a “bag of worms” (“vein filled sac”) o Cause: incompetent/congenitally absent valves in spermatic veins (the valves that prevent backflow are absent/don’t function, permitting blood to pool in the veins rather than flow into the venous system) o Can cause infertility Hydrocele: collection of fluid w/in the tunica vaginalis, most common cause of scrotal swelling (“water filled sac”) o Cause: In newborns it’s a congenital malformation that usually resolves within 1 year. IN adults, may be caused by an o o o o o o imbalance between the secreting/absorptive capacities of scrotal tissues. An infection/trauma may also cause. Spermatocele: painless cyst located between the head of the epididymis and the testis that’s filled w/ milk fluid that contains sperm (“sperm filled sac”) Cryptochidism Testicular maldescent (testis don’t drop) Cause: could be physical (spermatic cord too short) or hormonal (maternal gonadotropins are missing) Risk of testicular cancer is 35-50 times greater for men with undescended testis Ectopy Testis that have “strayed” from the normal pathway of descent Cause: may be an abnormal connection at the distal end of the gubernaculum (a fibrous cord that connects testis with bottom of scrotum) that leads the gonad to an abnormal position Torsion of tests A rotation of the testis, which twists blood vessels in the spermatic cord, can be very painful & serious b/c it cuts off blood supply If it can’t be fixed manually, surgery is performed within 6 hours after onset of symptoms Orchitis Inflammation of the testes, uncommon except when infection is present or there is an extended problem relating to epididymitis Sudden onset after a mumps infection can occur Cancer of the testes What is it? Among the most curable of cancers (cure rates are more than 95%), pretty rare occurrence (1%) but most common cancer in men aged 1535, white men are at higher risk than black men, more common on the right side & 50% arise from treated/untreated cryptorchid testes Mechanism? Most are germ-cell tumors arising from the male gametes. Can be classified into two types: o Seminomas: most common, least aggressive o Nonseminomas: include embryonal carcinomas, teratomas and choriocarcinomas (most aggressive but rare) Metastasis can occur and does so through lymphatic spread & the lungs are common sites for the cancer to travel to Believed to have genetic predisposition Symptoms? Painless testicular enlargement (gradual), actuve pain can occur, lumbar pain may be present, may have a cough/bloody sputum (sign of spread to the lungs), neck swelling, alterationsin vision/mental status Treatment? Surgery, radiation & chemo Epididymitis Inflammation of the epididymis, generally in sexually active adult males Cause is usually STD bacteria that has spread to the epididymis Complications include abscess formation, infarction of the testis, recurrent infection and infertility Treatment may include elevating testes, bed rest, antibiotics, abscess draining Disorders of the prostate gland o Benign prostatic hyperplasia (BPH) What is it? Enlargement of the prostate gland Becomes problematic as the prostatic tissue compresses the urethra Prevalence in US men 60+ years old is about 50% (90% of men by age 70 have this issue), so it’s very common Mechanism? Aging/circulating androgens disrupt the balance of growth factor signaling pathways creating a growth-promoting/tissue remodeling microenvironment (leading to increased prostate volume) Eventually the bladder will be unable to empty all of the urine & increased volumes are retained (which is why some old men can take so long using the bathroom; they feel the urgency to urinate but can’t) Symptoms/Treatment? Weak urinary stream, abdominal straining, incomplete bladder emptying, repeated urination, over years the bladder will retain urine to the point of incontinence, bladder may swell and constrict surrounding structures Smaller glands may be treated with laser therapy/microwave thermotherapy, larger glands may be removed surgically, hormone therapy (antiandrogen agents block androgens at prostate and causes it to shrink) o Prostatitis Inflammation of the prostate, usually limited to a few of the gland’s excretory ducts Characterized as: Acute bacterial prostatitis: ascending infection of the urinary tract that occurs in men between ages 20-50 (also associated with BPH in older men) o Infection stimulates inflammatory response in which prostate becomes enlarged, tender and firm o Can be serious if infection spreads (septicemia) Chronic bacterial prostatitis: recurrent urinary symptoms/persistence of pathogenic bacteria in urine or prostatic fluid o Most common recurrent urinary tract infection in men o Usually caused by prostatic calculi so it’s hard to treat, may have to surgically remove the calculi stones Non bacterial prostatitis: prostatic inflammation without evidence of bacterial infection o Most common prostatitis syndrome o Caused by a reflux of sterile urine into the ejaculatory ducts as a result of high pressure voiding Prostatodynia (pain in the prostate) is sometimes considered a form of prostatitis May be caused by spasms in the genitourinary tract or tension in the muscles of the pelvic floor rather than a pathologic condition o Cancer of prostate in the US it’s the most common cancer in males, accounts for 15% of all cancer deaths (only lung cancer accounts for more), 75%+ of all prostate cancer is diagnosed in men older than 65, black men have highest rates of prostate cancer in the world considered a disease associated with aging, thought to metastasize by local extension/through lymphatic & blood vessels (often asymptomatic until it’s too late) Dietary/Environmental Factors Worldwide distributions points to dietary issues involved Risk factors include: high intake of fat, high Ca+ levels, low intake of dietary fiber & complex carbohydrates, high intake of protein, consumption of excess calories, low levels of sun exposure Smoking, excessive drinking and pesticides (carcinogens) can play a role as well Hormonal Factors Higher levels of circulating androgens and estrogens seem to have a negative affect Has not be thoroughly studied yet Vasectomy It’s unlikely that it plays a causal role but it may contribute to the condition Genetic/Epigenetic Factors Strong genetic predisposition present This is a complicated condition with lots of factors/inter-workings present. It’s best to read the section from P865 (pathogenesis) to P869 to fully understand. Sexual Dysfunction in Men P869-870 Defined as the impairment of any or all of the sexual response processes: erection, emission & ejaculation In men older than 40 years, organic factors are involved in more than 50% of cases: o Vascular, endocrine, and neurologic disorders Any disruption in vasculature can prevent blood from entering shaft, therefore preventing erection Endocrine problems that reduce testosterone production can affect libido/sexual function Spinal cord injury, tumors, multiple sclerosis, peripheral neuropathies all affect sympathetic/parasympathetic/CNS mechanisms & can lead to erectile disorders o Chronic disease (including renal failure and diabetes mellitus) o Penile diseases/penile trauma Infections that cause fibrous tissue to develop, Peyronie disease, any damage to the erectile tissue o Iatrogenic factors (surgery, pharmacologic therapies) Impairment of Sperm Production & Quality P870-871 Spermatogenesis requires adequate secretion of FSH/LH by the pituitary & sufficient secretion of testosterone by the testes. This process depends not only on the appropriate stimulation (so the gland will release the hormone) but also on the appropriate response of target organ. o Fertility is adversely affected if spermatogenesis is normal but the sperm are chromosomally/morphologically abnormal or are produced in insufficient quantities o Sperm motility is also an important variable (motility is affected by sperm’s chemical environment or semen) Disorders of the Female (and Male) Breast P871-909 Galactorrhea: persistent/excessive secretion of a milky fluid from the breasts of a women who isn’t pregnant (can occur in men too) o Most common cause is nonpuerperal hyperprlactinema (excessive amounts of prolactin in blood). May be caused by Drugs (phenothiazine, estrogen, narcotics and tricyclic antidepressants) Hypothyroidism (causes hypoth to release TRH that stimulates prolactin release) Pituitary tumors (prolactin secreting tumors, putting pressure on pituitary, etc.) Chronic stress: inhibits PIF (prolactin inhibiting factor) Persistent/repeated sucking/squeezing of nipples on daily basis o Women may experience irregular period, milky breast secretion, headaches, visual field disturbances and sleep disturbances Benign breast disease (BBD): noncancerous changes in the breast o Nonproliferative (fibrocystic changes): benign alterations in ducts/lobules occur in the breast that occur with the menstrual cycle (so a kind of waxing/waning affect going on) Common symptoms reported are pain, palpable mass or nipple discharge, sometimes there is inflammation from a ruptured cyst (most women have this and it’s not serious) o Proliferative breast lesions w/out atypia Characterized by proliferation of ductal epithelium and/or stroma w/out cellular signs of malignancy. Classified in the following ways: Epithelial hyperplasia: presence of more than 2 cell layers above basement membrane, moderate to florid hyperplasia is more than 4 cell layers above basement membrane Sclerosing adenosis: number of acini per terminal duct is greater than twice the number found in uninvolved lobules, calcification is common but normal lobular arrangement is maintained Radial scar: irregular, radial proliferation of ductlike small tubules entrapped in a dense fibrosis Papillomas: multiple finger-like projections/branching axes lined by myoepithelial cells and luminal cells o Proliferative breast lesions w/ atypia: there is abnormal structure present Atypical hyperplasia (AH): increase in the number of cells w/ some variation in cellular structure, women with AH have a 4x increased risk in developing cancer Ductal hyperplasia: increase number of cells mostly within the lumen of the terminal ducts Lobular hyperplasia: proliferation of small, uniform cells in the lumen of lobular units o Treatment consists of relieving symptoms, changing diet, cysts will usually disappear w/out treatment Cancer (really complicated section, might want to review P880-908) o Breast cancer is the most common cancer in American women, leading cause of death for ages 40-44, & 2nd most common killer of women (lung cancer is first) o Risen steadily since 1950 (probably due to more diagnosis these days) and leveling off at 126 cases per 100,000 women. Lifetime risk is 1 in 8 for white women, lower for black women o Breast cancer can spread to almost anywhere in the body, but most likely goes to the bone, lungs, lymph nodes, brain and liver This is why it must be treated as a systemic (rather than localized) disease o Risk factors include: Reproductive: nulliparous women are at greater risk (or women who have their 1st child past 30), the younger the woman is for her 1st birth the less her risk Stem cells are the origin for breast cancer. It’s believed that early pregnancy reduces stem cells Age and reproduction is also suggested to affect lobular involution (breast epithelium atrophies/disappears). The more involution/higher rate a woman experiences involution, the lower her risk of breast cancer Hormonal: oral contraceptive & estrogen replacement therapy may be risks The key here is tissue remodeling that applies to pubertal growth, immediately after pregnancy and during involution Also important to note that women with higher mammographic density (less fat) have a higher risk of breast cancer Environmental: environment influence most high during differential stages (puberty, pregnancy, lactation, involution and menopause) Radiation: exposure to ionizing radiation increases risk (especially during pregnancy/adolescence) Diet: o Small relationship between dietary fat and risk (due to high concentrations of fat-soluble chemicals found in the breast) o Obesity reduces risk of premenopausal breast cancer, BUT increases risk in postmenopausal women o Alcohol consumption increases risk (b/c it hinders the liver’s ability to di the body of cancer-causing agents & impairs immune system) o Soy consumption may decrease risk Chemicals: long standing exposure is the key o o o o o Includes pollution, pesticides, fuels, plastics, detergents and drugs Lifestyle: regular physical activity may reduce risk Familial: history of cancer in 1st degree relatives increases risk 2/3 times Genes responsible for inherited cancer syndromes appear to be tumorsuppressor genes Black women have 32% higher death rate from breast cancer than white women Breast cancer pts younger than 35 have a worse prognosis than older pts Ductal carniomas in situ (DCIS): heterogeneous group of proliferations limited ot the ducts/lobules Lobular carcinoma in situ (LCIS): originates from the terminal duct-lobular unit (unlike DCIS, LCIS has uniform appearance and occur in noncohesive clusters in lobules) Inflammatory stroma in breast cancer: early alterations in stroma that occur with wound healing/inflammation may contribute (in other words, inflammation stimulates tumor cells) Invasive breast carcinoma: malignant, invasive epithelial lesion derived from terminal duct lobular unit Disorders of the Male Breast P908 Gynecomastia: overdevelopment of breast tissue in male , affects 30-40% of male population o Results from hormonal alterations (which may be idiopathic or result from systemic disorders, drugs or neoplasms) o Usually involves imbalance of estrogen/testosterone ratio Cancer: male breast cancer accounts for 1% of all male cancers and less than 1% for all breast cancers combined