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OUTLINE
INTRODUCTION
FUNCTIONAL ANATOMY
HORMONAL PRODUCTION
MENSTRUAL CYCLE
PUBERTAL DEVELOPMENT
MENSTRUAL ABNORMALITIES
ESTROGEN REPLACEMENT THERAPY
INTRODUCTION
→Oval organs →Lie in the pelvic fossa →Paired organs that perform gamete (ovum) & steroid hormone production →Unlike in males, the primordial reproductive cells in females typically produce a solitary gamete → FORMED BY ▪ Posterior & lateral pelvic wall → ATTACH TO ▪ Posterior surface of the broad ligament by thre peritoneal fold known as mesovarium → POSITION ▪ Near th fimbral end of the fallopian tubes connected to uterine cavity → ADULT OVARY ▪ LENGTH: 2- 5 cm ▪ WEIGHT: 14g ▪ CONTAINS: 2 - 4 million primordial cells
FUNCTIONAL ANATOMY
→ OVARIAN & MENSTRUAL EVENTS
▪ Carefully synchronized by a complex interplay of hormones among the hypothalamus, pituitary, & ovaries ▪ To prepare the uterus for implantation of an embryo ▪ Absence of implantation leads to shedding of uterine lining, thus menses → LENGTH OF MENSTRUAL CYCLE ▪ Time between any 2 consecutive cycles ▪ Typical duration is 28 (±3) days w/ average menstrual flow about 2-4 days → PRIMORDIAL FOLLICLES ▪ Present at birth ▪ Maturation is blocked until puberty ▪ Following onset of puberty, each ovarian cycle is marked by recruitment of a few primordial follicles for maturation → FOLLICULAR PHASE ▪ Primordial follicels are recruited after maturation ▪ All but one (Graafian follicle) of these follicles will atrophy ▪ GRAAFIAN FOLLICLE IS COMPOSED OF ✓ Theca externa- outer ✓ Theca interna- inner ▪ Maturing ovum attaches to the inside of the follicle via cells derived from granulosa cells (Cumulus cells) → LUTEAL PHASE ▪ In response to ovarian stimulation by LH, Graafian follicle releases its ovum ▪ The theca & granulosa cells of the Graafian follicle undergoes hypertrophy to become the corpus luteum (Luteinization) ▪ Corpus luteum is rich in cholesterol ▪ Corpus luteum acts as a substrate for continued production of progesterone & estrogen, maintaining the endometrium for conception ▪ If no conception or implantation, endometrium is shed & corpus luteum atrophies to an atretic follicle XY XX SRY MIS MALE FEMALE Encases the granulosa layer (layer of cells) a central fluid-fille cavity Primordial follicles containing primary oocytes 2 ND^ MEIOTIC DIVISON STARTS 1 ST^ MEIOTIC DIVISON STARTS OVULATION Corpus Luteum albicans^ Corpus Secondary follicle Early Primary follicle FSH, LH If no fertilization Secretion at Sexual maturity At birth, no further development until sexual maturity Graafian follicle secondary oocyte^ containing Primary follicle
HORMONAL PRODUCTION
1) ESTROGEN
2) PROGESTERONE
3) ANDROGENS
4) OTHERS
ESTROGEN
→Produced by follicle →Naturally Synthesized Estrogens →C-18 compound →Responsible for the follicular changes in the uterus during the reproductive period →Promotes breast, urine, & vaginal development →Affects skin, vascular smooth muscles, bone cells, & CNS → ESTRADIOL- principal estrogen produced by ovary → ESTRONE & ESTRIOL- primary metabolites of intraovarian & extraglandular conversion → LACK OF ESTROGEN ▪ Naturally occurs w/ onset of menopause ▪ Leads to atrophic changes in organs → DURING REPRODUCTIVE PERIOD ▪ Responsible for follicular phase changes in uterus ▪ Deficiency results in irregular & incomplete development of the endometrium
PROGESTERONE
→Produced by corpus luteum →C-21 compound w/I the steroid family →Induces secretory activity of endometrial glands that have been primed by estrogen →Readies the endometrium for embryo implantation →Promotes thickening of the cervical mucus and reduction of uterine contraction →Marker of ovulation →Dominant hormone in luteal phase →Deficiency results in failure of implantation of embryo
ANDROGENS
→ PRODUCES C-19 COMPOUNDS
▪ Androstenedione (Precursor to estradiol) ▪ Dehydroandrostenedione ▪ Testosterone ▪ Dihydrotestosterone (DHT) → EXCESS ANDROGEN IN WOMEN LEADS TO ▪ Excess hair growth (hirsutism) ▪ Loss of female characteristics ▪ Development of overt male secondary sexual features ✓ Masculinization ✓ Virilization ▪ Unlike estrogen, w/c is not produced in the ovary after menopause, ovarian androgen synthesis continues well into advanced age
OTHER HORMONES
→INHIBIN A & B
▪ Produced by the ovaries ▪ Inhibits FSH production
→ACTIVIN
▪ Enhances FSh secretion ▪ Induces steroidogenesis → HORMONES THAT APPEAR TO HAVE IMPORTANT, YET NOT CLEALY CHARACTERIZED FUNCTIONS ▪ Folliculostatin ▪ Relaxin ▪ Follicle-regulatory protein ▪ Oocyte Maturation Factor ▪ Meiosis-inducing substance
MENSTRUAL CYCLE
→ OVARIAN CYCLE
▪ Follicular phase ▪ Luteal phase → UTERINE/ENDOMETRIAL CYCLE ▪ Proliferative phase ▪ Secretory phase
FOLLICULAR PHASE
→Begins with onset of menses →Ends with LH surge →Early phase, the ovary secretes little estrogen →A rise in FSH stimulates follicular growth & estrogen production → ESTROGEN IS SECRETED BY THE FOLLICLE ▪ Stimulates uterine epithelial cells ▪ Growth of blood vessels ▪ Development of endometrial gland PROGESTERONE PRODUCTION OVULATION egg is released from the biggest follicle & travels through the fallopian tube where it can be fertilized. It is not fertilized and dissolves in about 24-48 hours FOLLICULAR PHASE This is when several eggs mature inside small cysts or follicles MENSTRUATION This is the “period” when the endometrium or lining of the uterus sheds over 3-7 days if there is no pregnancy LUTEAL PHASE This is when the endometrium (lining of the uterus) is thick & prepared to support a pregnancy or be released in a period OVARIAN CYCLE BODY TEMPERATURE AP HORMONES (GONADOTROPIC) OVARIAN HORMONES UTERINE CYCLE PHASES OF THE UTERINE CYCLE PROLIFERATIVE PHASE^ SECRETORY PHASE Inhibin PRIMARY FOLLICLE THECA (^) ANTRUM MATURE
→ OLIGOMENORRHEA- Irregular menstrual bleeding w/ cycle
length 35 - 40 days
→ MENORRHAGIA- Uterine bleeding >7 days
INFERTILITY
CAUSES
TARGET RESULT CAUSE
Hypothalamus ▪ GnRH ▪ Drugs
▪ Increased tress
▪ Diet
Pituitary ▪ FSH & LH ▪ Destructive tumor
▪ Vesicular lesion
Ovaries ▪ estradiol &
progesterone
▪ Organ failure
▪ Organ dysgenesis
▪ Anti-ovarian antibodies
▪ Malnourishment
▪ Very low weight
▪ Metabolic disease
Fallopian tubes
Uterus
▪ Inadequate
endometrium
▪ Low progesterone
output
▪ Cervical infections
▪ Pelvic inflammatory
disease
Conception ▪ Immobilization
▪ Destruction of sperm
▪ Antisperm
antibodies
HYPOGONADOTROPIC HYPOGONADISM
→ FSH & LH
→ Estrogen & Progesterone
→ CAUSES
1) Secondary Amenorrhea
2) Pituitary tumors
3) Weight loss (Anorexia nervosa)
4) Intense physical exercise (Runner’s amenorrhea)
5) Prolactinomas
HYPERGONADOTROPIC HYPOGONADISM
→ FSH & LH
→ Estrogen & Progesterone
→Ovarian failure
▪ Premature menopause
▪ Turner’s syndrome
POLYCYSTIC OVARIAN SYNDROME
▪ Reverse with weight loss & increased physical activity
▪ Infertility
▪ Chronic anovulation
▪ Hirsutism
▪ Glucose intolerance
▪ Hyperlipidemia
▪ Hypertension
HIRSUTISM
→Abnormal, abundant, androg-n sensitive terminal hair growth
in areas
in which terminal hair follicles are sparsely distributed or not
normally
found in women
→Should only be considered in the context of a woman’s ethnic
origin
→ POSSESS MORE ANDROGEN-SENSITIVE TERMINAL HAIR THAN
MOST NORTHERNERN EUROPEAN WOMEN
▪ Italian
▪ Eastern European
▪ Eastern Indian
▪ Irish
→ 5 - 10% of American women have hirsutism quantified using
Ferriman-Gallwey Scale
→Idiopathic etiology (60%)
→PCOS (35%)
CAUSES
COMMON UNCOMMON
▪ Idiopathic
▪ PCOS
▪ Drugs (Danazol)
▪ OCP w/ androgenic progestins
▪ Congenital adrenal hyperplasia
▪ Hyperprolactinemia
▪ Cushing syndrome
▪ Adrenal tumors
▪ Ovarian tumors
ANDROGEN LEVELS IN HIRSUTISM AND VIRILIZATION
ANALYTE
CONDITION TOTAL
TESTOSTERONE
FREE
TESTOSTERONE
DHEAS
Idiopathic hirsutism^ ^
PCOS ^ ^
Congenital adrenal
hyperplasia
VIRILIZING TUMORS
Ovarian ^ ^
Adrenal ^ ^
FERRIMAN-GALLWEY SCALE
→ NINE AREAS EVALUATED IN FERRIMAN-GALLWEY SCALE
▪ Lip ▪ Lower back
▪ Sideburn ▪ Chest
▪ Chin ▪ Thigh
▪ Neck ▪ Abdomen
The cause isn’t clear but may be genetic. In some cases, the condition seems to be linked to weight gain. The most common symptom is irregular periods. CYSTS IN OVARY ACNE DEPRESSION INFERTILITY Physical & pelvic examinations and blood tests are done to check hormone levels OTHER SYMPTOMS Too much hair on face, chest, & stomach Usually starts in women younger than 30. It is a hormonal condition in which ovaries have fluid-filled sacs (cysts)
▪ Upper back
→A score of 1- 4 is given for nine areas of the body
→A total score of <8 is considered normal
→A score of 8 - 15 indicates mild hirsutism (consistent w/ diagnosis)
→A score >15 indicates moderate or severe hirsutism
→A score of 0 indicates absence of terminal hair
UPPER LIP^1 Small no. of terminal hairs over upper lip & outer lip border
2 Thin moustache Covers <50% of upper lip or at the outer border 3 Moustache covers 50% from outer margin of the lip or 50% of the lip height 4 Moustache covers most of the lip & crossing the lip height
SIDEBURN AREA^1 Sparse terminal hairs
2 Sparse terminal hairs w/ small, thickened areas 3 Light hair growth over sideburn area 4 Thick growth over sideburn area ]
CHIN^1 Sparse terminal hairs
2 Sparse terminal hairs w/ small, thickened areas 3 Entire chin covered w/ light growth 4 Entire chin covered w/ heavy growth
LOWER JAW & NECK^1 Sparse^ terminal^ hairs^ over^ lower^ jaw^ &
upper neck 2 Sparse terminal hairs w/ small, thickened areas 3 Entire area covered w/ light growth 4 Entire area covered w/ heavy growth
UPPER BACK^1 Sparse terminal hairs^ on terminal back
2 Increased number of spread terminal
hairs
3 Entire area covered w/ light growth
4 Entire area covered w/ heavy growth
LOWER BACK^1 Sacral area w/ hair coverage^ <4cm
wide
2 Increased side coverage
3 75% of LB covered w/ terminal hairs
4 Entire area covered w/ heavy growth
CHEST^1 Circumareolar or midline terminal hairs
2 Circumareolar and midline terminal
hairs
3 75% of chest covered w/ terminal hairs
4 Entire area covered w/ terminal hair
growth
THIGH^1 Scattered terminal hairs over <25% of
thigh
2 Increased but incomplete coverage
3 75% of LB covered w/ terminal hairs
4 Entire area covered w/ heavy growth
UPPER ABDOMEN^1 Scattered midline terminal hairs
2 More terminal hairs, still midline
3 50 % of UA covered
4 Entire area covered w/ terminal hair
growth
LOWER ABDOMEN^1 Small terminal hairs^ number the length of linea alba^ of^ scattered^ midline
2 Midline concentration of terminal hair the length of the linea alba 3 A middle-thickened band od terminal hair <^1 / 2 width of pubic hair at base 4 An inverted V-shaped coverage 1 / 2 width of pubic hair at base
PERINEUM^1 Scattered perianal terminal hairs
2 Spread of terminal hair to the gluteal
cleft
3 75% of perineum covered w/ terminal
hairs
4 Entire area covered w/ terminal hair
growth
UPPER ARM^1 Scattered terminal hairs over <25% of
UA
2 Increased but incomplete coverage
3 75% of LB covered w/ terminal hairs
4 Entire area covered w/ heavy growth
ESTROGEN REPLACEMENT THERAPY
→HORMONE REPLACEMENT THERAPY
▪ Reductions in bone loss, colon polyp formation, &
menopausal symptoms (hot flashes & vaginal dryness)
▪ Decreased progression of subclinical atherosclerosis in
women started < or = 6 years of menopause ELITE trial
(Early versus Late Intervention Trial with Estradiol)
▪ Increased evidence of invasive breast cancer (hazard
ratio is 1.26), stroke, venous clot formation, CHD, & no
benefit in cognitive decline
-------- NOTHING ELSE FOLLOWS --------
