Chapter 27 Female Reproductive System II Lecture 20 Marieb’s Human Anatomy and Physiology Marieb w Hoehn Chapter 27 Female Reproductive System II Lecture 20 Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1] Slides 16 – 38; 50 min [Lecture 2] 118 min (38 slides plus review of course Web sites and syllabus)

Lecture Overview Hormonal control of the female reproductive system Mammary glands Male and female climacteric Birth control Sexually transmitted disease (STD) A brief review of the ovarian cycle before we begin…

Review of Female Reproductive Cycle Figure from: Hole’s Human A&P, 12th edition, 2010

Ovarian Cycle – Preovulatory (Follicular) Phase Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001 (Graafian) 1.5 cm Many Few One Thecal and granulosa cells produce estrogens 8-10 days after beginning of cycle 10-14 days (FSH) (FSH) LH Meiosis II started Meiosis I Estrogen

Ovarian Cycle – Postovulatory (Luteal) Phase (Day 14) 12 days post ovulation Lipids used to synthesize progestins, e.g., progesterone (prepares uterine lining for implantation) LH If fertilization has not occurred LH Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Hormonal Control of the Female Reproductive Cycle Ovarian and uterine (menstrual) cycles must be coordinated GnRH (Gonadotropin Releasing Hormone) is the controlling hormone of reproduction Pulse frequency and amplitude (amount) Without pulses, LH/FSH secretion (also in pulses) will stop Changes in GnRH pulse frequency are controlled by estrogen (increase) and progestins (decrease)

Hormonal Regulation of Ovarian Activity Figure from: Saladin, Anatomy & Physiology, McGraw Hill, 2007

Hormonal Regulation of Ovarian Activity inhibits LH and FSH during most of the reproductive cycle Estrogen is the predominant hormone prior to ovulation (follicular phase) Progesterone is the predominant hormone after ovulation (luteal phase) 1-4 GnRH pulses/day (Day 10) 36 GnRH pulses/day 48GnRH pulses/day 16-24 GnRH pulses/day At 16-24 pulses/day of GnRH, secretion of FSH predominates (2), and the estrogen produced by the developing follicle inhibits LH release. At 36 pulses/day of GnRH (caused by increasing estrogen from tertiary follicles), LH secretion is stimulated and the previously inhibitory effect of estrogen on LH secretion now becomes stimulatory. When GnRH is pulsing at about 48 pulses/day, there is massive release of LH from ant. Pit. Causing LH surge, triggering ovulation about 34-38 h afterwards. Figure from: Marieb, Anatomy & Physiology, Pearson, 2004

Pathways of Steroid Hormone Synthesis Most abundant Androstenedione is secreted by thecal cells (LH) of the primary follicles and then absorbed by the granulosa cells (FSH) and converted to estrogens. Note three major female hormones; estradiol is most abundant Cooperation of thecal and granulosa cells Under influence of LH, thecal cells secrete androstenedione Granulosa cells convert androstenedione into estradiol Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Effects of Estrogens (20 sex characteristics) development of breasts and ductile system of the mammary glands increased adipose tissue in breasts, thighs, and buttocks increased vascularization of skin Maintenance of the function of accessory reproductive glands/organs CNS effects, e.g., sex drive, “feminization” Repair/growth of endometrium (following menses)

Uterine (Menstrual) Cycle Figure from: Hole’s Human A&P, 12th edition, 2010 Functional Basilar * Proliferative phase – functional layer of endometrium thickens under the influence of estrogen Secretory phase – Arteries elaborate and uterine glands enlarge, coil, and begin secreting glycogen under progesterone’s influence

Menarche and the Menstrual Cycle First menstrual cycle (Latin mensis = month) Typically begins around age 11-12 If menarche does not appear by age 16, considered amenorrhea (rhe(o)- = flow) Menstrual cycles Occur monthly unless interrupted by illness, stress, starvation, or pregnancy Lack of menstrual period for 6 months or more is considered amenorrhea (secondary) Painful menstruation is called dysmenorrhea – may result from uterine inflammation or conditions involving adjacent pelvic structures Menarche does not appear until females have accumulated about 17% body fat; adult menstruation generally ceases if a woman’s body fat drops below 22%. The formula to predict your body fat percentage, based on your current BMI, age, and gender (from http://www.halls.md/bmi/fat.htm): Child Body Fat % = (1.51 x BMI) - (0.70 x Age) - (3.6 x gender) + 1.4 Adult Body Fat % = (1.20 x BMI) + (0.23 x Age) - (10.8 x gender) - 5.4 where male gender= 1, female=0.

Overview of Female Reproductive Cycle Figure from: Hole’s Human A&P, 12th edition, 2010 You should understand these events, and their timing, for the exam

Events of the Female Reproductive Cycle Table 22.4 in Hole’s Anatomy & Physiology Good textual review table for combined ovarian and uterine cycles Figure from: Hole’s Human A&P, 12th edition, 2010

Male and Female Climacteric Female climacteric = menopause usually occurs in late 40s or early 50s (perimenopause) reproductive cycles stop for 6 months to 1 year ovaries no longer produce as much estrogen and progesterone due to depletion of ovarian follicles some female secondary sex characteristics may disappear sustained rise in GnRH and LH/FSH may produce hot flashes (LH) and fatigue risk of atherosclerosis increases hormone therapy may prevent effects on bone tissue Female climacteric begins when a female has about 1,000 eggs left (rather than at a specific age). From http://emedicine.medscape.com/article/264088-overview#aw2aab6b4: Over time, as aging follicles become more resistant to gonadotropin stimulation, circulating FSH and LH levels increase. Elevated FSH and LH levels lead to stromal stimulation of the ovary, with a resultant increase in estrone levels and a decrease in estradiol levels. Inhibins are peptides of the transforming growth factor (TGF)-β superfamily and are produced by the granulosa cells of the ovarian follicles in the terminal stages of development. Inhibin levels also drop during this time because of the negative feedback of elevated FSH levels.[1, 2, 14] With the commencement of menopause and a loss of functioning follicles, the most significant change in the hormonal profile is the dramatic decrease in circulating estradiol, which rapidly declines over a period of 4 years (starting 2 years before the final menstrual period and stabilizing approximately 2 years after the final period). Without a follicular source, the larger proportion of postmenopausal estrogen is derived from ovarian stromal and adrenal secretion of androstenedione, which is aromatized to estrone in the peripheral circulation. Total serum testosterone levels do not change during the MT. Dehydroepiandrosterone (DHEAS) levels do decline with age. A trend toward higher total cholesterol, low-density lipoprotein (LDL), and apolipoprotein B levels, in conjunction with loss of the protective effect of high-density lipoprotein (HDL), is characteristic in menopause.[1, 2, 15] With cessation of ovulation, estrogen production by the aromatization of androgens in the ovarian stroma and estrogen production in extragonadal sites (adipose tissue, muscle, liver, bone, bone marrow, fibroblasts, and hair roots)[15]continue, unopposed by progesterone production by a corpus luteum. Consequently, perimenopausal and menopausal women are often exposed to unopposed estrogen for long periods, and this exposure can lead to endometrial hyperplasia, a precursor of endometrial cancer. Although estradiol levels decrease significantly because of the loss of follicular production with menopause and postmenopause, estrone, which is aromatized from androstenedione from nonfollicular sources, is still produced and is the major source of circulating estrogen in the postmenopausal female. Because most conversion of androgens to estrogens occurs in adipose tissue, it is frequently assumed that obese women, who have more circulating estrogen, should have fewer complaints of vasomotor symptoms. However, this is not always the case, and vasomotor symptoms of menopause can be as frequent and severe in heavier women as they are in thinner women. The clinical indication that menopause has occurred is a rise in the measured FSH level. The FSH level rises more than the LH level because of the reduced renal clearance of FSH in comparison with LH. A slightly elevated or borderline menopausal FSH level in the MT may not be a reliable indicator of menopause, because of the wide variation of FSH and LH levels in response to increased release of gonadotropin-releasing hormone (GnRH) by the hypothalamus and increased pituitary sensitivity to GnRH. Male climacteric (andropause) more gradual than female climacteric usually occurs after age 50 slowly declining levels of testosterone sperm (gamete) production continues (even into 80s!)

Mammary Glands Mammary glands as shown are for women in last trimester of pregnancy or who are nursing. The areola, a ring of pigmented skin, covers large sebaceous glands that give it a bumpy appearance. Sebum reduces chapping and cracking of the nipple. Blood capillaries and nerves come closest to the surface of the skin in the area surrounding the nipple, giving the areola a reddish brown color. Darkening of the areola and nipple during pregnancy help the nursing infant locate the nipple since their vision might not otherwise be able to distinguish this area from the remainder of the breast. Sensory nerve fibers of the areola trigger the milk letdown (ejection) reflex. Bumps on the areola are a result of sebaceous/sweat (areolar) glands in this area. Sebaceous glands help keep the nipple from drying and cracking during nursing. Figures from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Mammary Glands Figures from: Martini, Anatomy & Physiology, Prentice Hall, 2001 Milk production = lactation Inactive (resting) mammary gland is dominated by a duct system rather than by active glandular cells. Size of mammary glands in a nonpregnant/nonlactating woman reflects amount of adipose tissue present.

Clinical Application – Breast Cancer Malignant cancer of the mammary gland (ducts/glands) Second leading cause of death in women (exceeded only by lung cancer) Death rates declining, especially in women under 50 (perhaps due to better screening) Risk factors Family history Early menarche and/or late menopause First pregnancy later in life No proven link between oral contraceptive use, estrogen therapy, fat consumption, or alcohol use; but these are suspected links About a 20% less risk after menopause in women who have nursed their babies Self examination and mammography help in early detection (< 2 cm) and reduction in mortality

Breast Cancer Screening Recommendations In addition to guidelines below, women should consider having a baseline mammogram in their late 30s Figure 3.1: Breast Cancer Screening Recommendations for Women at Average Risk     Susan G. Komen for the Cure®  American Cancer Society    National Cancer Institute   National Comprehensive Cancer Network   U.S. Preventive Services Task Force   Mammography    Every year beginning at age 40. Every 1-2 years beginning at age 40. Every year beginning at age 40.  Informed decision-making with a health care provider ages 40-49.   Every 2 years  ages 50-74. Clinical Breast Exam   At least every 3 years  ages 20-39 Every 3 years  ages 20-39.   No specific recommendation. Every 1-3 years ages 20-39. Not enough evidence to recommend for or against. Note: Women at higher risk may need to get screened earlier and more frequently than recommended here. Find more on screening recommendations for women at higher risk of breast cancer. Table source: http://ww5.komen.org/BreastCancer/GeneralRecommendations.html

Breast Cancer Figure from: Hole’s Human A&P, 12th edition, 2010 Figures from: Saladin, Anatomy & Physiology, McGraw Hill, 2007

Birth Control abstinence (0%!!!)* coitus interruptus (?!) * Numbers in parentheses below indicate the approximate failure rate of the birth control method, i.e., percent of pregnancies abstinence (0%!!!)* coitus interruptus (?!) rhythm method (~25%) mechanical barriers condom (6-17%) diaphragm (5%) cervical cap (8%) chemical barriers - spermicidal foams or jellies (~ 26%) oral contraceptives (2-3%) hormonal injectable contraception (<1%) contraceptive implants (<1%) intrauterine devices (5-6%) surgical methods (sterilization) vasectomy (.08%) tubal ligation (.45%) For the rhythm method: abstinence must be practiced 7 days before ovulation (to be sure there are no surviving sperm) and 2 days after ovulation (to be sure there is no viable egg present).

Prevalence of Birth Control Methods

Reality™ - the Female Condom Excerpts from the Instruction Booklet… Use a new Reality with each and every sex act. Read instructions carefully before using Reality. The booklet explains how to use Reality. Don't tear Reality. Reality only works when you use it. Make sure Reality is not twisted after insertion. Reality should not be noisy during sex. Reality may shift during sex. Keep Reality out of the reach of children.

Surgical Methods of Birth Control Figure from: Hole’s Human A&P, 12th edition, 2010 Tubal Ligation failures: Sterilization failures can be grouped into the following categories: (eMedicine.com) - Luteal phase pregnancy is defined as a pregnancy in which conception occurs before the BTL, but pregnancy is diagnosed after an interval tubal sterilization. Strategies to reduce the incidence (reported to occur at a rate of 1-15 cases per 1000 interval sterilizations) include effective contraception, scheduling of BTL during the proliferative phase, and preoperative urine enzyme-linked immunoassay pregnancy testing. - Misidentification of the oviduct because of poor visualization from inadequate exposure, adhesions, adnexal pathology, or poor lighting may result in mistakenly ligating the round ligament, ovarian ligament, infundibular ligament, or dilated broad ligament blood vessels instead of the oviduct. Therefore, initially identifying the fimbriated tubal ends and then tracing the tube medially to the isthmic region is imperative. In postpartum minilaparotomy BTL, Babcock clamps should be placed sequentially along the oviduct until the fimbria is visualized. - Incomplete occlusion of the oviduct occurs because of poorly placed mechanical clips or the use of mechanical devices on edematous or dilated tubes. With correct clip application, the mesosalpinx on the surface of the tube is pulled upward to resemble the flat triangular shape of an envelope flap (the Kleppinger envelope sign). When silastic rings are used, the tubal serosa, but not the tubal lumen, may be pulled into the ring, with absence of the vertical crease formed when the entire loop of tube is included in the ring. - Incomplete tubal occlusion with electrocoagulation is generally associated with too brief an application of current or with the use of modulated/coagulation current instead of unmodulated/cutting current. - Improper technique occurs with the use of the wrong sutures or failure to preserve a 2-cm proximal tubal segment. If a short proximal stump is left, the fluid pressure from uterine contractions could either prevent complete closure of the tubal lumen during healing or cause a fistula to form to relieve pressure after healing is complete. Vasectomy failures: Although uncommon, recanalization may cause vasectomy failure in a small percentage of cases:  Surgical error, infidelity, and not using a back-up method of contraception for at least 12 weeks following a vasectomy are all possible reasons for pregnancy after the procedure. But most of the few vasectomy failures that happen are caused by recanalization, a spontaneous reconnection of the two ends of the vas, most often occurring within a month or two of a vasectomy. The risk of recanalization appears to be related to the surgical techniques used during the procedure. Fascial interposition can reduce the risk of failure, as defined by semen analysis, by about 50 percent when performed with ligation and excision [3].  Using cautery instead of ligation and excision may further reduce the risk of failure, making vasectomy an even more effective contraceptive method.  Still, couples should be counseled about the possibility of vasectomy failure so that an unexpected pregnancy is not automatically assumed to be the result of infidelity. Vasectomy Tubal ligation Newer techniques using silicone plugs may allow reversal of a vasectomy

When Other Methods of Birth Control Fail…

Sexually Transmitted Diseases (Infections) silent infections (incubation period and communicable period) most are bacterial and can be cured herpes, warts, and AIDS are viral and cannot be cured many cause PID (women) and infertility AIDS causes death symptoms of STIs typically include burning sensation or pain during urination pain in lower abdomen fever or swollen glands discharge from vagina or penis pain, itch, or inflammation in genital or anal area sores, blisters, bumps or rashes itchy runny eyes

Overall U.S. Trends in STDs Figure from: http://www.avert.org/std-statistics-america.htm Figure from: http://www.dermnet.com/topics/genital-warts/overview/ Figure from: http://wellness-reviews.com/std-testing/top-5-reasons-people-avoid-std-testing/

Review inhibits LH and FSH during most of the reproductive cycle Estrogen is the predominant hormone prior to ovulation (follicular phase) Progesterone is the predominant hormone after ovulation (luteal phase) (Day 10) Estrogen maintains secondary sex characteristics in females Figure from: Marieb, Anatomy & Physiology, Pearson, 2004

Review Figure from: Hole’s Human A&P, 12th edition, 2010

Review Climacteric Women Men Called menopause Occurs around 40-50 years of age Cessation of reproductive cycles – no oocytes Ovaries no longer produce much estrogen Men Occurs more gradually Sperm production continues well into old age Levels of testosterone decline gradually