NR 507 Final Study Guide

• The production of estrogen and progesterone continues until the placenta can adequately maintain hormonal production. If conception and implantation do not occur, the corpus luteum degenerates and ceases production of progesterone and estrogen. Without progesterone or estrogen to maintain it, the endometrium becomes ischemic and disintegrates. Menstruation then occurs marking the beginning of another cycle. ▪ Ovulatory cycles appear to have a minimum length of 24 to 26.5 days: the primary ovarian follicle requires 10 to 12.5 days to develop, and the luteal phase appears relatively fixed at 14 days (+/- 3 days). Menstrual blood flow usually lasts 3-7 days, but it may last as long as 8 days or stop after 1 to 2 days and still be considered within normal limits. ▪ Ovulation – the release of an ovum from a mature follicle and marks the beginning of the luteal/secretory phase. o Uterine prolapse ▪ Descent of the cervix or entire uterus into the vaginal canal. ▪ In severe cases, the uterus falls completely through the vagina and protrudes from the introitus. ▪ Symptoms of other pelvic floor disorders also may be present. • Urinary: sensation of incomplete emptying of the bladder, urinary incontinence, urinary frequency/urgency, bladder “splinting” to accomplish voiding • Bowel: constipation or feeling of rectal fullness or blockage, difficult defecation, stool or flatus incontinence • Urgency: manual “splinting” of posterior vaginal wall to accomplish defecation • Pain & Bulging: vaginal, bladder, rectum; pelvic pressure, bulging, pain, lower back pain • Sexual: dyspareunia, decreased sensation, lubrication, arousal ▪ Tx: • Kegel exercises • Estrogen to improve tone and vascularity of fascial support • Pessary • Weight loss • Avoidance of constipation o Polycystic ovarian syndrome ▪ Most common cause of anovulation and ovulatory dysfunction in women. ▪ Defined as having at least two of the following three features: irregular ovulation, elevated levels of androgens (testosterone), and the appearance of polycystic ovaries on ultrasound. ▪ Polycystic ovaries do not have to be present to diagnose PCOS, and conversely their presence alone does not establish the diagnosis. ▪ Initial identification of genes involved in steroid biosynthesis, androgen biosynthesis, and insulin receptors within the ovary indicates genetic involvement. ▪ A hyperandrogenic state is a cardinal feature in the pathogenesis of PCOS. ▪ However, glucose intolerance/insulin resistance and hyperinsulinemia often run parallel to and markedly aggravate the hyperandrogenic state, thus contributing to the severity of signs and symptoms of PCOS. ▪ Excessive androgens affect follicular growth, and insulin affects follicular decline by suppressing apoptosis and enabling follicles to persist. ▪ Weight gain tends to aggravate symptoms, whereas weight loss may ameliorate some of the endocrine and metabolic events and thus decrease symptoms. ▪ Women with PCOS tend to have increased leptin levels. Leptin influences the hypothalamic pulsatility of GnRH and consequent interaction along the entire HPO axis. ▪ In PCOS there is dysfunction in ovarian follicle development. Inappropriate gonadotropin secretion triggers the beginning of a vicious cycle that perpetuates anovulation. ▪ Typically, levels of FSH are low or below normal and LH levels and LH bioactivity are elevated. An increased frequency of GnRH pulses appears to cause increased frequency of LH pulses. Persistent LH elevation causes a increase in the levels of androgens. Androgens are converted to estrogen in peripheral tissues, and increased testosterone levels cause a significant reduction in SHBG, which in turn causes increased levels of free estradiol. ▪ Elevated estrogen levels trigger a positive-feedback response in LH and a negative-feedback response in FSH. ▪ The accumulation of follicular tissue is various stages of development allows an increased and relatively constant production of steroids in response to gonadotropin stimulation. Thus PCOS is characterized by excessive production of both androgen and estrogen. ▪ In turn, persistent anovulation causes enlarged polycystic ovaries characterized by a smooth, pearly white capsule. This characteristic appearance is caused by an increase of surface area and increased volume of up to 2.8 times, doubling of growing and atretic follicles, thickening of the tunica by 50%, increasing cortical stromal thickening by one-third and a fivefold increase in subcortical stroma, and escalating hyperplasia. ▪ Manifestations: • Usually appear within 2 years of puberty but may present after a variable period of normal menstrual function and possibly pregnancy. • Symptoms are related to anovulation, hyperandrogenism, and insulin resistance and include dysfunctional bleeding or amenorrhea, hirsutism, acne, acanthosis nigricans, and infertility. ▪ Eval & Treatment: • Diagnosis is based on evidence of androgen excess, chronic anovulation, and sonographic evidence of polycystic ovaries with at least 2 of the 3 criteria present. • Tests for impaired glucose tolerance are recommended. • Evidence of hyperandrogenism must be present before PCOS is diagnosed in an adolescent female. • Goals of tx: reversing signs and symptoms of androgen excess, instituting cyclin menstruation, restoring fertility, and ameliorating any associated metabolic or endocrine, or both, disturbances. • First line: combined oral contraceptives for management of symptoms and to establish regular menses. • For those women with PCOS who are overweight or obese, lifestyle modifications including regular exercise and weight loss, also are considered first- line treatment. o Testicular cancer and conditions that increase risk ▪ Highly treatable, usually curable cancer that most often develops in young and middle-aged men ▪ 90% of testicular cancers are germ cell tumors arising from the male gametes. ▪ In addition, testicular tumors can arise from specialized calls of the gonadal stroma. These tumors, which are named for their cellular origins are Leydig cell, Sertoli cell, granulosa cell, and theca cell tumors and constitute less than 10% of all testicular cancer. ▪ Risk factors: history of cryptorchidism, abnormal testicular development, human immunodeficiency virus (HIV) and AIDS, Klinefelter syndrome, and history of testicular cancer. ▪ Manifestations: • Painless testicular enlargement is usually the first sign. • Enlargement is usually gradual and may be accompanied by a sensation of testicular heaviness or dull ache in the lower abdomen. • Lumbar pain may be present and usually is caused by retroperitoneal node metastasis. • Signs of metastasis to the lungs: cough, dyspnea, hemoptysis • Supraclavicular node involvement: dysphagia, neck swelling • Metastasis to CNS: alterations in vision, mental status, papilledema, and seizures o Symptoms that require evaluation for breast cancer ▪ The first sign of breast cancer is usually a painless lump. Lumps caused by breast tumors do not have any classic characteristics. ▪ Chest pain (lung metastasis) ▪ Dilated blood vessels ▪ Dimpling of the skin ▪ Edema ▪ Edema of the arm ▪ Hemorrhage ▪ Local pain ▪ Nipple/areolar eczema ▪ Nipple discharge in nonlactating woman ▪ Nipple retraction ▪ Pitting of the skin (peaud’orange) ▪ Reddened skin, local tenderness, and warmth ▪ Skin retraction ▪ Ulceration o Signs of premenstrual dysphoric disorder ▪ >/= 5 symptoms below: occur in most cycles during the week before menses onset, improve within a few days after menses onset, and diminish in the week postmenses • Marked affective lability • Marked irritability or anger or increased interpersonal conflicts • Marked anxiety, tension • Decreased interest • Difficulty concentrating • Easy fatigability, low energy • Increase or decrease in sleep • Feelings of being overwhelmed • Physical symptoms: breast tenderness, muscle or joint aches, “bloating” or weight gain o Dysfunctional uterine bleeding (Abnormal uterine bleeding) ▪ Bleeding that is abnormal in duration, volume, frequency, or regularity and has been present for the majority of the previous 6 months. ▪ May be acute or chronic and is classified by PALM-COEIN system: • Polp • Adenomyosis • Leiomyoma • Malignancy • Hyperplasia • Coagulopathy • Ovulatory dysfunction • Endometrial • Iatrogenic • Not-yet classified ▪ In premenstrual or menopausal women, any bleeding is considered abnormal. Therefore bleeding more frequently than every 21 days or less frequently than every 35 days, is considered to be abnormal. Menstrual bleeding for longer than 7 days also is considered abnormal. ▪ AUB is the leading reason for hysterectomy. ▪ Perimenopausal women are most commonly affected. ▪ The majority of AUB is due to lack of ovulation. Normal, regular periods are the result of complex interplay between the hypothalamus, pituitary, ovary, and the uterine endometrium. Disruptions in this system can affect the amount and structure of the uterine endometrium, causing it to shed irregularly or heavily. ▪ If a follicle forms but never releases the ovum, the follicle may continue to produce estrogen, encouraging endometrial proliferation beyond the normal 14-day time window. In addition, the lack of progesterone causes the thickened endometrium to be unable to shed in a predictable fashion without excessive blood loss. Women who fail to ovulate experience irregularities in their menstrual bleeding related to the lack of progesterone and, in some cases, an excess of estrogen. ▪ Without ovulation, menstrual flow may become irregular, excessive, or both, resulting from the large quantity of tissue available for bleeding and the random breakdown of tissue that results in exposure of vascular channels. In the absence of adequate progesterone levels, usual endometrial control mechanisms are missing, such as vasoconstrictive rhythmicity, tight coiling of spiral vessels, and orderly collapse, and stasis does not occur. ▪ AUB also can result from defects of the corpus luteum, resulting in progesterone deficiencies, or from abnormalities of the uterus or cervix, such as endometrial polyps, uterine fibroids, or even uterine or cervical cancers. ▪ Coagulation defects also can cause heavy and abnormal uterine bleeding and should be suspected in younger women with a history of extensive bruising or bleeding during dental procedures. Iatrogenic AUB can be caused by intrauterine devices or long-acting contraceptive implants or medications, such as anticoagulants, steroids, digitalis, phenytoin, or hypothalamic depressants. ▪ Manifestations: • Unpredictable and variable bleeding • Increased menstrual flow and the passage of large clots, leading to excessive blood loss • Pain, decreased productivity, and sexual dysfunction ▪ Eval & Tx: • 1st step in assessing AUB is determining the cause of the bleeding. • Treatment goals include preventing or controlling abnormal bleeding, identifying underlying disease, and inducing regular menstrual cycles. • NSAIDs, such as ibuprofen and naproxen, are often 1st-line treatment for excessive menstrual bleeding because they reduce prostaglandin synthesis within the endometrial tissues, which causes vasoconstriction and decreased menstrual blood loss. NSAIDs can reduce menstrual bleeding significantly with minimal side effects. For the best effect, they should be taken in the few days preceding the beginning of the menstrual period and be continued through the days of heaviest bleeding. NSAIDs are not as effective in controlling menstrual blood loss as hormonal therapies. • Young women and those of childbearing age with abnormal bleeding are often treated with hormonal therapies to override the HPG axis and mimic normal menstrual bleeding or suppress it entirely. Common treatments include oral contraceptive pills that contain both estrogen and progesterone, long-term treatment with medroxyprogesterone and the levonorgestrel intrauterine device. • Women who do not wish to have future pregnancies can opt for treatments that permanently suppress their uterine lining. These treatments include ablation, where the lining is burned to prevent future proliferation of the endometrial cells, and complete removal of the uterus in hysterectomy. • If a woman is menopausal, and has not had a menstrual period for more than 1 year, all vaginal bleeding should be investigated to rule out uterine and other cancers. • Women with coagulation disorders may have excessive menstrual bleeding because they have a predisposition to bleeding or because they are taking anticoagulant medications to overcome a genetic predisposition to excessive clotting. To control their menstrual bleeding, these women can opt for cycle suppression. o Pathophysiology of prostate cancer ▪ One of the most common forms of cancer occurring in the male. ▪ Prostatic cancer occurs in older men, is slow growing, and is not highly invasive. ▪ Individuals experiencing this cancer typically have high levels of prostatic-specific antigen in their blood. ▪ Most occur in the periphery of the prostate. o HPV and the development of cervical cancer ▪ Cervical cancer is almost exclusively caused by cervical human papillomavirus (HPV) infection. Infection with high- risk types of HPV is a necessary precursor to development of cervical dysplasia, otherwise known as the precancerous cell changes that lead to invasive cancer. ▪ Precancerous dysplasia, also called cervical intraepithelial carcinoma (CIN) and cervical carcinoma in situ (CIS), is a more advanced form of these cell changes. Importantly, cervical dysplasia can be detected noninvasively through examination of the cervical cells. If dysplasia is detected early, treatment is available to prevent invasive cancer. ▪ High-risk HPV may persist and cause abnormal cellular changes that can become cancerous. Most HPV infections are cleared by the immune system; the vast majority of infections do not cause cervical cancer. For this reason, screening for cervical cancer before age 21 is not recommended. ▪ Women with multiple sexual partners are more likely to be exposed to high-risk HPV, but women with only one lifetime sexual partner also can become infected. Smoking has been shown to increase the risks of persistent infection and later development of cervical cancer; in addition, women who have many children, have a long history of oral contraceptive use, and are immunocompromised also are at higher risk of cervical cancer. Women who use vaginal douches also seem to be at increased risk of HPV infection. ▪ HIV infection greatly increases the risk that women infected with HPV will develop cervical cancer, and women with HIV should be screened for cervical cancer more frequently more women without HIV. In addition, high-risk HPV is found more frequently in women who are coinfected with chlamydia or gonorrhea, suggesting that those infectious processes may support the persistence of HPV in those women. ▪ There are two main cell types: squamous epithelium cells and columnal epithelial cells. The line where the two cell types meet, known as the transformation zone, is very vulnerable to the oncogenic effects of HPV, and this is where carcinoma in situ is most likely to develop. ▪ Because metaplastic cells are at increased risk of incorporating foreign or abnormal genetic material, neoplastic changes are most common in the transformation zone. ▪ In girls and young women, a large portion of their cervix is covered with columnar epithelium, a condition known as squamous metaplasia. Therefore the younger a woman is when she contacts HPV, the more sensitive cervical cells are exposed. ▪ Manifestations: • Asymptomatic • PAP test necessary for early detection • If symptoms exist: vaginal bleeding or abnormal discharge. o Vaginal bleeding may occur after intercourse or between menstrual periods. o Vaginal discharge is a less common presenting symptom and may be serosanguineous or yellowish with a foul odor. ▪ Eval & Tx: • For women aged 30-65, HPV testing is now recommended at the same time as the Pap test because it is noninvasive and identifies women at later risk for cellular abnormalities leading to cancer; indeed, HPV is often detectable for more than a decade before any noticed cellular changes. For women aged 21-29, HPV testing is only indicated if a PAP test is abnormal, which is known as reflex HPV testing. • Cervical cytologic exam is most accurate if cells are obtained from both the endocervix and ectocervix, • Endocrine: which involves placing the collection device into the cervical os. • When dysplasia is detected, further testing is indicated for diagnosis. o Body’s process for adapting to high hormone levels ▪ Negative feedback is the most common and occurs when a changing chemical, neural, or endocrine response decreases the subsequent synthesis and secretion of a hormone. ▪ High concentrations of hormone decrease the number or affinity of receptors called downregulation. o Cushing’s Syndrome ▪ Clinical manifestations resulting from chronic exposure to excess endogenous cortisol and is more common to women. ▪ Whatever the cause, 2 observations apply: (1) they do not have diurnal or circadian secretion patterns of ACTH and cortisol, and (2) they do not increase ACTH and cortisol secretion in response to a stressor. ▪ In individuals with ACTH-dependent hypercortisolism, secretion of both cortisol and adrenal androgens is increased, and corticotropin-releasing hormone (CRH) secretion is inhibited. ▪ Elevated cortisol levels suppress CRH and ACTH secretion from the hypothalamus and anterior pituitary, respectively, which leads to low levels of ACTH. Low levels of ACTH cause atrophy of the remaining normal portions of the adrenal cortex, which over time will alter the cortisol- secreting activity of normal cells. When the secretion of cortisol by the tumor exceeds normal cortisol levels, symptoms of hypercortisolism develop. ▪ Manifestations: • Weight gain is the most common feature and results from the accumulation of adipose tissue in the truck, facial, and cervical areas. These characteristic patterns of fat deposition have been described as “truncal (central) obesity,” “moon face,” and “buffalo hump” • Polyuria is a manifestation of hyperglycemia and resultant glycosuria. • Muscle wasting leads to muscle weakness and is especially obvious in the muscles of the extremities, with thinning of the limbs. • In bone, loss of protein matrix and increases in bone resorption lead to osteoporosis and can result in pathologic fractures, vertebral compression fractures, bone and back pain, kyphosis, and reduced height. • Hypercalciuria may result in renal stones. • With elevated cortisol levels, vascular sensitivity to catecholamines is increased significantly, leading to vasoconstriction and hypertension. • Metabolic syndrome with abdominal obesity, hypertension, glucose intolerance, and dyslipidemias is a common complication. • Chronically elevated cortisol levels also cause suppression of the immune system, increased susceptibility to infections, and poor wound healing. • Females may experience symptoms of increased adrenal androgen levels, increased hair growth (facial hair), acne, and oligomenorrhea. • Infertility is common among women. ▪ Eval & Treatment: • Tests: urine and serum cortisol and serum ACTH concentration • Treatment is specific for the cause of hypercorticoadrenalism and includes medication, radiation, and surgery