Repro Flashcards

Question

# Sexual Differentiation & Disorders by Dr Gillott What is Gonadal dysgenesis ## Footnote *LOB Relate the process of sexual differentiation to clinical disorders

Answer 1

Incomplete differentiation Missing SRY (male) Partial or complete deletion of second Y (female) Used as general word for abnormal development

Answer 2

Phenotype not congruent with genotype

Answer 3

Components of both tracts or ambiguous genitalia

Answer 4

Disorder of Sexual Differentiation NOT ‘pseudohermaphrodite’ or ‘testicular feminisation'

Answer 5

SRY present Sertoli produce AMH **AMH regresses Mullerian** Leydig produce Testosterone **Testosterone DOESNT develop Wolffian** DHT present **DHT doesnt produce external genitals** **ANDROGEN INSENSITIVITY SYNDROME** 1:20,000 Phenotypically female AFAB Primary amenorrhea, lack of body hair Often ID as female | Why no external? Same receptor, Receptor broken

Answer 6

1:20,000 Phenotypically female AFAB Primary amenorrhea, lack of body hair Often ID as female Undecended testes (U/s) "Male" Karyotype Not surgically reassigned unless option explored w gender ID. Partial AIS | Why no external? Testosterone receptor broken

Answer 7

SRY present Sertoli and AMH present Leydig and Testosterone present Normal internal stucture- epididymus, testis **Testosterone to DHT fails** External genitalia -> phenotypically feminine No fusion of labial scrotal folds No testicular decent

Answer 8

Incidence varies as autosomal recessive Degree of enzyme block varies and therefore so does presentation High testosterone and adrenarche may cause distress

Answer 9

XO Ovaries Female External genitalia Failure of ovarian function **TURNER SYDNROME** May be fertile, may be moasaicism Small ovaries with growth defects and development Hormone support of bones and uterus required.

Answer 10

45 XO Ovaries Female External genitalia Failure of ovarian function May be fertile, may be moasaicism Small ovaries with growth defects and development Hormone support of bones and uterus required.

Answer 11

45XO has error but 46XX has natural repression of one X But cross over for psuedoautosomal region at the gene Has a biological impact on expression ? full purpose unknown

Answer 12

Congenital adrenal hyperplasia Dont be scared of Steroids Produces Ovary Doesnt produce AMH- Mullerian (internal female) Testosterone so Wollfian grow as well DHT present- external male genitalia

Answer 13

**Cholesterol 3 6-sided rings 1 5-sided ring And a chain** All the progestorins are 3 6-sided rings and 1 5-sided ring. They dont have the chain How they differentiate? The enzymes move where the oxygens live Remove 2 more carbons: Have all the androgens like testosterone. How are they different? Enzymes move where the Oxygens live Remove 1 more carbon: You have Oestrogens!!!! Name ends with -one??? Ketone so has =o Name ends with -iol?? Has 2 OH groups

Answer 14

Adrenal glands cannot transform the cholesterols. No cortisol? High levels of ACTH Lots of cholesterol brought in Progestorins build up Androgens build up in foetus adrenal cortex Produces lots of testosteone (no oestrogen as aromatase not present)

Answer 15

Until puberty

Answer 16

Neuroendocrine

Answer 17

Kisspeptin was found to play a role in hypogonadotropic hypogonadism around 2003 and its involvement in the hypothalamic pituitary axis and sexual maturation was uncovered. Influences Hypothalamus to release GnRH

Answer 18

Connect to GnRH Express kisspeptin ? Role in puberty Smae amino terminal but different sizes

Answer 19

Pulsatile release 30-120 minutes Stimulates LH and FSH Slow Pulse: FSH > LH *(F for fast but its actually slow)* High Pulse: LH > FSH If given constantly- shuts down the pituitary Receptor is G Protein so decouples G Protein from secondary messenger

Answer 20

FSH and LH released in response to GnRH Proteins

Answer 21

Transition from non-reproductive to reproductive state Profound physiological and psychological changes Secondaary characteristics development

Answer 22

**Adrenarche** From the adrenal glands maturation of cells Release of androgens leads to ***pubarche***: appearance of pubic and axillary hair **Gonadarche** Follows adrenarche HPG Driven LH FSH Activate gonadal function

Answer 23

**LH** stimulates gonadal steroid synthesis and secondary sex characteristics **FSH** stimulates growht of testis and folliculogenesis with steroid synthesis

Answer 24

Change in adrenal secretion Zona reticularis develops as adrenarche occurs Secretion of DHEA (pubarche) Increases from 10 y.o. to mid 20s then declines through life Sometimes acne **Causes** ?Unknown molecular Body weight Leptin, insulin??? Normal remodelling

Answer 25

**Sebaceous PSU** glands that secrete for hair sudden increase of angrogens over production of sebum ***acne*** **Vellous PSU** Fine hair that cover body Androgen exposure develops for terminal PSU (**beard**) develops for Apocrine (**axillary and pubic hair**) scent glands

Answer 26

HPG first activated at 16wk until 1-2y.o GnRH neurones are restrained until 10 y.o Reactivated at **Gonadarche** Rise in pulsative GnRH release ?????Kisspeptine role????? Activation of gonadal steroid production Production of viable gametes

Answer 27

Epiphysal Fusion "Growth Spurt" Ends of long bones As oestrogen levels become higher you get epiphyseal fusion and growth stops. Higher oestrogen in females so epiphyseal fusion occurs earlier- smaller height in women.

Answer 28

Theoretically... **Genetic**: maturation of GnRH neurones, environmental/ genetic factors **Body fat**/ Nutrition: earlier as nutrition improved, 17-18% fat and 22% to maintan menstrual cycle- link with leptin **Kisspeptin** potential activates GnRH neurones

Answer 29

Progression of changes Order of changes that happen remains the same

Answer 30

**Examining a patient** Uses shape and size of external genitals Shape and size of breasts Sexual Hair

Answer 31

**GnRH- dependent (central)** Excess GnRH- idiopathic or secondary Excess Gonadotrophin secretion- pituitary tumour Maintains consonance Accelerated linear growth, advanced bone ages, increased FSH, LH, estradiol and testosterone Use GnRH analogues until later age Surgery, radio or chemotherapy

Answer 32

Testoxicosis activating mutation of LH receptor leading to early androgen production No FSH (no spermatogenesis) Causes Sex steroid secreting tumour or exogenous steroids – secondary sexual characteristics McCune Albright - constitutive activation of adenylyl cyclase - hyperactivity of signalling pathways including those of gonadotrophin hormones. Congenital adrenal hyperplasia – androgen production by the adrenal glands.

Answer 33

More common in boys Absence of secondary sex maturation by 14 yo (m), 13 yo (f) or absence of menarche by 18 yo Constitutional Delay- secondary to chronic disease Hypogonadotrophic hypogonadism - low LH, low FSH, low activation of gonads Hypergonadortophic hypogonadism- high LH, high FSH, Klinefelter XXY, Turners, **gonadal dysgenesis**, mumps

Answer 34

Period of time from changes in menstrual pattern to menopause

Answer 35

A period of changing ovarian function preceding menopause by 2-8 years Not consistently defined

Answer 36

Permenant cessation of menstruation due to loss of ovarian follicular function Amenorrhoea for 12 months Retrospective diagnosis (Think contraception)

Answer 37

Menopause < 40 yo

Answer 38

Sometimes none Reduced cycle length- **Reduced follicular phase** Some experience irregular periods with episodes of amenorrhea- **why?** Year before: hot flushes, distrubed sleep -**declining oestrogen** Dry Vagina -**oestrogen declined** Impaired fertility

Answer 39

**Reduced number of follicles per ovary** Due to increased cell death Increased follicular recruitment **Reduced number and function of granulosa cells** Low AMH -> High FSH Low Inhibin A and B -> High FSH Reduced Oestrogen and Progesterone for survival factors for ovum Fewer FSH receptors impair recruitment **Oocyte Function** Lack of growth factors / impaired from granulosa Increased anueploidy Impaired follicle recruitment Anovulatory cycles and increased miscarriage rate.

Answer 40

**Shortened Cycle (early MT)** Decline in inhibin B (granulosa) Increased FSH in follicular Early elevated oestrogen and early LH surge **Delayed/ Absent Ovulation (late MT)** Oestrogen early in cycle by high FSH but levels dont induce GnRH surge (impaired granulosa) Ovularion delayed/ not occuring FSH insensitivity due to fewer granulosa cell receptors **Heavier periods** Longer oestrogen stimulation of endometrium **Breast tenderness** Transitiory increases oestrogen for long time **Hot fluses** Low oestrogen -> serotonin disturbance, resets thermoregulatory nucleus

Answer 41

AMH levels first show declining ovarian function Inhibin B declines FSH vary each cycle, increasing towards menopause LH increases but later in menopause Oestrogen falls close to menopause No progesterone after menopause

Answer 42

**HRT** **Non-Hormonal ** incl clonidine, SSRI, SNRI, Gabapentin **Non Pharm** Phytoestrogens (soya), Herbal (Black cohosh, St Johns Wort) **Behavioural** CBT, Hypnotherapy

Answer 43

60-80% efficacy reducing hot flushes FHx Risk of cancer **Progesterone use for 13 days with Uterus as protects against Endometrial Hyperplasia- 56% . ** Contraception if < 1 amennhorea Low dose to avoid mastalgia, nausea, Low risk for short term use, **Combined Oestrogen and Progesterone HRT** Continous combined or Cyclical Progesterone **Oestrogen Alone**

Answer 44

* ??? Chronic disease prevention * Licensed for menopausal symptoms only * Increased risk of breast cancer and stroke/ thrombosis * Alzheimers- NO RCT, no cognitive impact * Worsening of prevalent incontinence and no change in incident incontinence with HRT * Non-significant increase in ovarian carcinoma in users of combined HRT * Oestrogens prevent osteoporosis just while being used * Endometrial Hyperplasia- 56% . But protection with 10-13 days progesterone * Gain in QoL from sleep, nil else

Answer 45

Fezolinetant is a non-hormonal neurokinin 3-receptor antagonist that modulates neuronal activity in the hypothalamic thermoregulatory centre. ◦ MHRA approved 2023 ◦ Awaiting NICE appraisal so currently only pp. ◦ No long term data on safety

Answer 46

* selection of a single oocyte * correct number of chromosomes in eggs i.e. haploid * regular spontaneous ovulation * cyclical changes in the vagina, cervix and Fallopian tube * preparation of the uterus * support of the fertilised dividing egg

Answer 47

Feedback loop between Hypothalamus, Ant Pituitary and the Ovary, led by GnRH, FSH/ LH, Oestrogen and Progesterone

Answer 48

When GnRH is continuous, it causes levels of LH to drop due to desensitisation of the pituitary gland

Answer 49

Cyclical 2 Phases: follicular and luteal, seperated by ovulation. In a 28 day cycle, day 1 is 1st day menses

Answer 50

Growth of antral follicles up to ovulation Dominanted by oestradiol production from antral follicles Approx 14 days. Ends with Ovulation (middle of the cycle)

Answer 51

formation of corpus luteum from the remaining cells of follicle dominated by progesterone production from corpus luteum Occurs after Ovulation, Approx 14 days Menstruation if no pregnancy

Answer 52

**Luteal phase** Negative feedback by Progesterone **Follicular phase=variable** 1. Release/removal of negative feedback 2. Negative feedback is reinstated, then 3. Switch from negative to positive feedback

Answer 53

Raised FSH present a “window” of opportunity to recruit antral follicles that are at the right stage to continue growth Oestradiol levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth

Answer 54

* One follicle from the group of antral follicles in ovary is just at the right stage at the right time to survive declining FSH * This becomes the dominant follicle which goes onto ovulate * Known as “selection” * Can be in either ovary

Answer 55

LH increases DF acquires LH receptors on granulosa cells Other follicles do not, so they lose their stimulant and die

Answer 56

If oestrogen levels are high enough long enough (threshold) Triggers pituitary to start an LH rise LH increase causes 3' follicle to "pop' Ovulation

Answer 57

* Egg is released * Large rise in LH = luteinisation i.e. formation of the corpus luteum * Corpus luteum has both luteinised granulosa and theca cells * E2 production falls, but still produced and Progesterone is stimulated & dominates

Answer 58

* blood flow to the follicle increases dramatically * appearance of apex or stigma on ovary wall * Local release of proteases and inflammatory mediators * Enzymatic breakdown of protein of the ovary wall * 12-18 hrs after peak of LH, the follicle wall is digested and ovulation occurs with release of cumulus-oocyte complex (COC) * Oocyte with COC extruded * Follicular fluid may pour into pouch of douglas, * Egg collected by fimbria of uterine tube * Egg progresses by peristalsis and cillia action

Answer 59

After ovulation the follicle collapses Progesterone production increases greatly E2 increases CL contains many LH receptors, so only requires low LH levels If pregnancy occurs, hCG bing to LH receptors to maintain it

Answer 60

Maternal steroids increase size of new-born uterus. Grows with height during infancy. Myometrium dependent on estradiol. Corpus of uterus undergoes greater increase in size than cervix.

Answer 61

Outer muscular myometrium grows gradually throughout childhood. Increases rapidly in size and configuration during puberty. Changes in size through the cycle. Capable of vast expansion during pregnancy. Inner layer circular fibres. Middle layer figure of 8 or spiral fibres. Outer layer longitudinal fibres.

Answer 62

Very thin in childhood. Begins to thicken at puberty. Dependent on steroids and responds cyclically to hormone changes. Estrogen principally causes growth in proliferative phase. Can be seen and measured on an ultrasound scan. Good ‘bioassay’ of estradiol level…7-16mm. Changes in glandular and epithelial cells through the cycle. Progesterone causes mainly differentiation in secretory phase. At menstruation most of the endometrium is lost. After menstruation - stromal matrix with small columnar cells with glandular extensions 2-3mm thick glands are simple and straight.

Answer 63

Proliferative phase (follicular phase of ovary) following menses. Stimulated by estrogen from the growing follicle. Stromal cell division, ciliated surface. Glands expand and become tortuous, increased vascularity, neoangiogenesis. Maximal cell division by days 12-14. When endometrium >4mm induction of progesterone receptors and small muscular contractions of the myometrium.

Answer 64

**Secretory phase (luteal phase of ovary) 2-3 days after ovulation, the gradual rise in progesterone causes a reduction in cell division.** Glands increase in tortuosity and distend. Secretion of glycoproteins and lipids commences. Oedema, increased vascular permeability, arterioles become increasingly convoluted to increase surface area. Myometrial cells enlarge and blood supply increases.

Answer 65

Corpus luteum stimulated by LH from pituitary during luteal phase. The fertilised oocyte becomes a blastocyst and produces human chorionic gonadotrophin (hCG) which acts like LH (binds to LH receptor) and ‘rescues’ the corpus luteum. In the absence of this, falling levels of steroid from the corpus luteum results in menstruation.

Answer 66

Prostaglandin release causes constriction of spiral arterioles. Hypoxia causes necrosis. Vessels then dilate and bleeding ensues. Proteolytic enzymes released from the dying tissue. Outer layer of endometrium shed, 50% lost in 24hrs, up to 80ml is considered normal. Bleeding normally lasts 4+ days. Basal layer remains and is then covered by extension of glandular epithelium. Estrogen from follicle in next follicular phase starts cycle off again.

Answer 67

Epithelial cells express high numbers of estrogen receptors & undergo differentiation in response to estradiol increase in height mid-cycle. Oocyte can only pass down the tube during mid-cycle. Cilia beat and secretory cells are active along with muscle layer contractions, all in response to estrogen. After a few days of exposure to progesterone the estrogen receptors are supressed and estrogen effects are overcome causing decrease in height mid-luteal onwards.

Answer 68

**Laparoscopy and dye** Combined Approach: Laparoscopy utilizes small incisions and a laparoscope, enhanced by injecting dye for improved visualization. Diagnostic & Surgical Benefits: Allows minimally invasive direct viewing of pelvic organs, aiding in both diagnosis and surgical procedures. **Hystero Salpingo-contrast Sonography (HyCoSy)** Fertility Assessment: Evaluates fallopian tubes and uterine cavity without invasiveness. It involves injecting a saline solution mixed with a contrast agent (usually a microbubble contrast agent) into the uterus through the cervix while simultaneously using ultrasound imaging to monitor the flow of the solution through the fallopian tubes. Alternative to HSG: Uses ultrasound instead of X-rays, comparable accuracy.

Answer 69

Muscular structure capable of great expansion. The endocervical mucosa is about 3mm thick, lined with a single layer of columnar mucous cells, containing numerous tubular mucous glands which empty viscous alkaline mucus into the lumen. Protective barrier to infection... However, it has to allow passage of motile sperm. The ectocervix is covered with nonkeratinized stratified squamous epithelium, resembling the squamous epithelium lining the vagina.

Answer 70

Estrogen in the follicular phase causes… Change in vascularity of cervix and oedema. Mid-cycle estrogen levels cause change in mucous to become less viscous. Change in mucous composition. Mucus contains glycoproteins glycoproteins which become aligned and form microscopic channels. Sperm swim up the channels!

Answer 71

Progesterone in luteal phase causes… Reduced secretion and viscous mucous (reduced water content). Glycoproteins now form mesh like structure: acts as barrier to sperm and microogranisms. One mechanism of action of oral contraceptives.

Answer 72

Thick-walled tube approx 10cm. Lined by specialised ‘squamous epithelial’ cells. Warm damp environment containing glycoprotein… Susceptible to infection, which is prevented by… Layers of epithelial cells shed constantly and ‘flow’ downwards with the secretions. Secretions are from cervix and transudation from vaginal epithelium. Secretions change with cycle and are generally acidic providing anti-microbial protection. Bartholins glands located slightly posterior and to the left and right of the opening of the vagina secrete mucus to lubricate the vagina and are homologous to bulbourethral glands in males.

Answer 73

The progenitor cell for ova and sperm Can ID in the yolk sac at 3 weeks Undergo many cycles of mitosis Migrate to the genital ridge in the foetus (becomes the Gonad)

Answer 74

Germ cells become oogonia when in the ovary Oogonia are ova-precursors Diploid, divide by mitosis **KNOWN AS PRIMARY OOCYTES when meiosis occurs** Following LH surge, Meiosis 1 and extrusion of first polar body

Answer 75

All the ova that will be possessed over a lifetime will be made at this stage Mitosis provides all the ova required

Answer 76

All the ova that will be possessed over a lifetime will be made at this stage Mitosis provides all the ova required Paused in Prophase 1 until LH surge

Answer 77

Primary oocytes remian in the first phase of meiosis (prophase 1) until ovulation (meiosis 1) or cell death Up to 52 years!

Answer 78

Each primary oocyte is surrounded by protective layers and cells In foetal ovary, surrounding cells condense and diffx into **Granulosa cells GC** The **GC** secrete acellular layer called **Basal Lamina** **This is the primordial follicle**

Answer 79

Growth and development of follicles from "resting" to ovulation Most follicles are not growing After puberty a cohort initiate growth each day

Answer 80

* Puberty- cohort of follicles initiate growth each day * Still Meiosis 1 * As follicles grow GC mutliple * Oocyte secretes protective acellular layer **Zona Pellucida** * A second layer of cells differentiate around the basal lamina forming the **Theca** (vascular) * Gaps form in granulosa layer called **Antrum, filled with Follicular fluid** and these are called **Secondary Follicles**

Answer 81

Enlarge whilst in Meiosis 1 Early factors are unknown FSH independent (follicles grow in FSH suppression- oestrogen dip in proliferative phase_ FSH drive the next phases 2 Phases of follicle grwoth are labelled by absence or presence of antrum

Answer 82

* Characterised by a cavity or “antrum” *Contains fluid formed as exudate of plasma containing secretory products of oocyte & GC *Known as “follicular fluid” *As follicular fluid volume and antrum expands, oocyte is displace to one side * A cohort of early antral follicles will reach the right stage and size that corresponds to the start of the intercycle rise in FSH. * These antral follicles continue growing. * This is known as follicle recruitment **One will be selected for Ovulation**

Answer 83

**Oocyte**- female germ cell **Theca Layer-** The theca interna contains steroidogenic cells that produce androgens, which are precursors to estrogen. **Basement Membrane**- structural support, regulate movement of molecules **Follicular Fluid**- hormones, nutrients, growth factors, and other molecules that support the growth and development of the oocyt **Granulosa Cell Layer**- support, interact w surrounding cells during fertilization, hormones

Answer 84

Theca Cells have LH Receptors and no FHS Receptors Granulosa cells have FHS Receptors and LHR (in midfollicular phase) 2 Cell 2 GnTrophin Theory Theca cells via LHR convert Cholesterol That converted molecule (androstenedione) is transported to Granulosa Cells FSH receptors can convert to Estradiol

Answer 85

Theca Cells have LH Receptors and no FHS Receptors Granulosa cells have FHS Receptors and LHR (in midfollicular phase)

Answer 86

The Graafian follicle is the follicle that ruptures during ovulation, releasing the secondary oocyte into the fallopian tube. After ovulation, if fertilization occurs, the Graafian follicle transforms into the corpus luteum, which plays a crucial role in supporting early pregnancy by secreting progesterone.

Answer 87

**Theca** contain enzymes to convert cholesterol to androgens **Granulosa** enzymes to convert androgens to estrogen INCL AROMATASE **Oovyte**- ? signalling role

Answer 88

- Follicle development begins with FSH stimulation. - Oocyte maturation involves meiosis I until ovulation (M2) - Ovulation is triggered by LH surge, releasing the oocyte. - Fertilization occurs when sperm penetrates the oocyte. - Chromosome number reduction happens during fertilization, where the secondary oocyte completes meiosis II.

Answer 89

* Ejaculated semen is coagulated * Movement through cervical mucus removes seminal fluid/ abnormal sperm and cellular debris * Cervical mucus is less viscous in the absence of progesterone allowing sperm to pass. * Can inhabit cervical crypts to form a reservoir (poorly understood) * ? Chemoattractants from oocyte cumulus complex may attract sperm (unkown) * Sperm hyperactivated * Fertilisation w/in 24-48 hr, sperm alive approx 5 days.

Answer 90

* Cervical crypts * Incorrect uterine tubule * ? chemoattractants * Capacitation 4-18 hours

Answer 91

* Removing the sperm from the seminal fluid * uterine or tubal fluid may contain factors which promote capacitation. * 4-18 hours * Biochemical rearrangement of the surface glycoprotein * and changes in membrane composition must occur * before the acrosome reaction can occur.

Answer 92

* Occurs in contact with the zona –cumulus complex * the acrosomal membrane on the sperm head fuses releasing * enzymes that cut through the complex. * Acrosin bound to the inner acrosomal membrane digests the zona pellucida so the sperm can enter

Answer 93

**Usually** 14 day life span Regression of CL essential for new cycle Stops progesteron production Endometrium is loss **In pregnancy: ** hCG (similar to LH, binds LHR) hCG binds to CL DOESNT DIE! Produced progesterone Maintained endometrium

Answer 94

1. The **acrosome reaction** occurs in contact with the zona-cumulus complex. Sperm penetrate cumulus and bind to ZP. 2. Sperm enzymes cut through ZP, fuses w plasma membrane 3. Sperm taken in by phagocytosis. Phospholipase Zeta activated by basal Ca2+ inside egg. PIP2 → DAG + IP3 Causes release of intracellular Ca2+ leading to large Ca2+ spike. 4. Cortical reaction as wave of Ca2+ sweeps around egg...release of proteases, peroxides and hyaline prevents polyspermy.

Answer 95

Entry of spark causesan increase Ca2+ in phospholipase Z from sperm Cas2+ causes completion of meiosis 2 expelling polar body Sperm nuclear membrane breaks down, chromatin decondenses and c.s separate 4-7 hours after sperm the two haploid c.s surrounded by membranes= pronuclei to synthesise DNA for mitosis Pronuclei fuse Mitosis occurs

Answer 96

1) fertilised egg w 2 pronuclei (in ampulla) 2) developing embryo contains 6-8 cells within 3 days (tubule) 3) Blastocyst approx 5 days (tubule to isthmus) 4) Blastocyst diffx ICM, blastocoel, trophoblast 5) READY TO IMPLANT

Answer 97

* Predicting fertile window to avoid * 7 days before ovulation and 1 day after * Ovulation is 14 days before period. * Monitor for 12 months first * Basal body temp, cervical mucus consistency, urinary LH detection * Failure rate 24% with typical use

Answer 98

**Condom** **Advantages**: * Protects against STIs * No serious health risks * Easily available **Disadvantages**: * Needs to be taught * May cause allergies * May cause psychosexual difficulties * Oily preparations rot rubber * Failure rate quite high with typical use **Diaphragm** Needs spermicide and left in 6 hours after SI **Advantage** Woman in control * Can be put in in advance * Offers protection against cervical dysplasias * No hormone **Disadvantage** Needs to be taught * Messy * Higher failure rate than most other methods * Higher UTI & Candidiasis MCondom failure 18% Perfect 2% FCondom Failure 12% Perfect 6%

Answer 99

Pill, Patch, Ring 12 days, 7 break (breaks can be 3 pack, 1 pack etc) Oestrogen and Progesterone Rings: 21:7 Patch changed weekly then 21:7 **Advantages** Reliable * Unrelated to coitus * Woman in control * Rapidly reversible * Halve cancer of ovary & endometrium risk * Helps endometriosis, premenstrual syndrome, dysmenorrhoea, menorrhagia Combined oral contraception **Disadvantage** * VTE PE MI Stroke Risk * Breast cervix liver Cancer risk * Mood and libido * Liver metabolism caution in LFT compromised * Many contraindications Failure 9%, Perfect 0.3%

Answer 100

Making cervical mucus hostile to sperm * Making the endometrium hostile to implantation * Reducing cilia motility in the fallopian tubes

Answer 101

* Making cervical mucus hostile to sperm * Making the endometrium hostile to implantation * Reducing cilia motility in the fallopian tubes * Inhibition of ovulation by feedback on the HPO axis (*main method of action of desogestrel and drosperinone but not of older POPs*) Taken continuously (except new DRSP) If missed >3 hrs 1st/2nd generation, >12 hrs desogestrel, >24hrs DRSP Condoms for 48 hrs **Advantages** * As effective as COCP * No oestrogen related CIs (e.g. VTE/migraine/BMI) * Favourable side effect profile in newer POPS **Disadvantages** * Systemic side effects (e.g. headache / bloating / acne) * Irregular bleeding Failure 9% Perfect 0.3% **Injection**: 13weeks or 8weeks (Failure 6% perfect 0.3%) **Implant**: 3 years (0.05% F and P)

Answer 102

* Lasts 5 years * Useful for menorrhagia and dysmennorhoea, endometriosis * Progesterone * "Mirena Coil" * May be expelled * The uterus may be perforated very rare * Miscarriage if left in situ if a pregnancy * If pregnancy occurs, more likely to be ectopic, but ectopic less likely than if no contraception **Absolute contraindications** * Current pelvic inflammatory disease * Suspected or known pregnancy * Unexplained vaginal bleeding * Abnormalities of the uterine cavity Failure 0.2% Perfect 0.2%

Answer 103

* Copper Coil * Lasts 5-12 years * Kills sperm in 1st part of the cycle; prevents implantation in 2nd part of the cycle * May cause bleeding to be heavier * Risks and CIs same as for hormonal IUS * Can also be used as emergency contraception Intrauterine device (IUD) – Copper bearing Failure 0.8% Perfect 0.6%

Answer 104

**Copper Coil/ IUD** within 5 days of UPSI or before est ovulation **Pills** Postponed ovulation- not effective after ovulation, Can be used twice if same cycle IF SAME TYPE **Levonorgestrel (Levonelle)*** * Can be taken up to 72 hours after UPSI * Can quick start contraception **Ulipristal acetate (EllaOne)** * Can be taken up to 120 hours after UPSI * More effective than levonelle * Need to defer starting hormonal contraception for 5 days

Answer 105

"male" sex hormone but testosterone is not exclusive Testes, ovary and the adrenal cortex secrete androgens

Answer 106

Testosterone is synthesised from cholesterol in Leydig cells. Secretions from the gonads are under the influence of follicle stimulating hormone (FSH) and luteinising hormone (LH) which are under the influence of gonadotropin releasing hormone (GnRH) Androgen secretions from the adrenal cortex is under the influence of adrenocorticotropic hormone (ACTH)

Answer 107

**High levels of testosterone in the blood feedback to the hypothalamus to suppress the secretion of GnRH and also feedback to the anterior pituitary, making it less responsive to GnRH stimuli.** * Throughout the reproductive life of males, the hypothalamus releases GnRH in pulses every 1 to 3 hours. Despite this pulsatile release, however, average plasma levels of FSH and LH remain fairly constant.

Answer 108

turn cholesterol into testosterone. * LH regulates the initial step in this process, by binding to LH receptors * This stimulates intracellular signalling pathways which promote cholesterol transport into mitochondria and increases transcription of genes involved in testosterone biosynthesis

Answer 109

Activated by FSH from the pituitary * Sertoli cells supply the developing germ cells with nutrients and growth factors. * Spermatogenesis is dependent on the presence of an adequate intratesticular level of testosterone. * Sertoli cells express the Androgen Receptor * Sertoli cells, in response to testosterone, will secrete inhibin B protein, this circulates in the blood and inhibits FSH production and secretion from the pituitary. Contributes to the negative feedback mechanism.

Answer 110

Steroid hormones cross into the cell cytoplasm where they will bind to their receptor 2. Binding to the receptor causes a conformational change in the nuclear receptor, causing it to become activated (some nuclear receptor dimerise at this point) 3. Nuclear receptors then translocate into the nucleus 4. Nuclear receptors bind to specific DNA sequences called response elements located in the promoters of steroid responsive genes. 5. Steroid responsive genes are switched on and upregulated.

Answer 111

When these receptors bind steroid hormones they are activated. – Thus they are called ligand-activated receptors – The binding of steroids to the ligand binding domain causes a physical restructuring of the polypeptide chains in the receptor, activating it

Answer 112

1. Ligand binding to the ligand binding site causes a shift in an a-helix, activating the receptor. 2. Receptor dimerises, moves into the nucleus and binds to specific DNA sequences 3. Receptor then recruits DNA modifying enzymes e.g. histone deacetylases, other transcription factors and RNA polymerase to promoters of hormone responsive genes.

Answer 113

Embryonic testes secrete testosterone, which drives differentiation and growth of the genital tissues and Wolffian structures. * Testosterone is responsible for the development of the male outer genitalia i.e. testes and phallus, as well as the inner genitalia e.g. prostate gland and seminal vesicles. * Without the SRY gene – the default developmental pattern is female.

Answer 114

Metabolism to the more potent agonist dihydrotestosterone (DHT) by 5alpha-reductase enzymes in target cells, drives the growth of the prostate, scrotum and phallus. * Reduced androgen signalling in males can result in undervirilization and infertility

Answer 115

Libido Growth of larynx Facial and body hair Muscle Mass Ext Genitalia

Answer 116

Genetically male, (XY). Are unable to respond to androgens, they may have mostly female external sex characteristics or signs of both male and female sexual development.

Answer 117

Mutations in the 5a reductase gene (SRD5A2). * Results in a spectrum of phenotypes including overt genital ambiguity, female appearing genitalia, & hypospadia. * Affected males still develop typical masculine features at puberty (deep voice, facial hair, muscle bulk) since most aspects of pubertal virilization are driven by testosterone, not DHT. * Either gender may be assigned at birth, or treatment with DHT may aid in development of male characteristics.

Answer 118

* Decreased hormonal output from the gonads * Decreased testosterone synthesis * Caused by genetic diseases, damage to testes, undescended testes, mumps, pituitary and hypothalamus abnormalities. * Requires testosterone supplementation

Answer 119

Early onset of puberty, with the associated development of secondary sexual characteristics * Due to genetic disorders, thyroid gland disorders, brain damage, brain tumours, gonadal tumours * Treated with agents to stop gonadotropin releasing hormone (GnRH antagonists).

Answer 120

Often women with polycystic ovary syndrome will produce excess androgens, due to ovulatory dysfunction and impaired folliculogenesis. * Leads to hirsutism, acne, & alopecia * May be treated with androgen receptor antagonists

Answer 121

Androgens are converted to more potent agonists at target tissues e.g. at the prostate, or at hair follicles. * This is done by the actions of 5a-reductase * DHT can damage hair follicles, resulting in alopecia * Finasteride is a 5a – reductase inhibitor, reduces DHT production at the site of hair follicles

Answer 122

Stable, synthetic androgen mimics * Used by body builders and athletes * Large doses may be effective in increasing muscle mass/athletic performance in some individuals * All anabolic steroids virilise (i.e., masculinise) * Attempts to separate the anabolic from virilising effects of anabolic steroids have been unsuccessful

Answer 123

Normal uses: wasting conditions, severe illness, anaemia, oedema, genetic diseases, hypogonadism, osteoporosis

Answer 124

Stanozolol, nandrolone and other anabolic steroids can be detected in the urine of athletes abusing these drugs Abuse of anabolic steroids cause the following: * ↓ testicular size and sperm count * Changes in libido, regression of testes with suppression of spermatogenesis * ↑aggression * Hepatotoxicity with cholestasis, hepatitis or hepatocellular tumours * ↑ LDL and ↓ HDL → vascular disease * Weight gain * Acne

Answer 125

In many cases, several androgens (e.g. testosterone, nandrolone, oxymetholone and stanozolol, etc.) are used for prolonged periods and their continuous use can cause: * Hypertension and oedema: testosterone and other anabolic steroids such as nandrolone, stanozolol have calcium, sodium, and water-retaining actions * Cholestatic jaundice: anabolic steroids (nandrolone, stanozolol) may lead to liver cancer * Suppression of gonadotrophin (FSH & LH) release with testicular regression and reduced spermatogenesis * Virilisation; hirsutism; male pattern baldness; acne * Premature closure of epiphyses of long bone in boys * Gynaecomastia – due to conversion of testosterone to oestrogens by aromatase

Answer 126

Testosterone is converted in the prostate to a more potent androgen – dihydrotestosterone – which drives prostate growth and function

Answer 127

The prostate gland is an androgen sensitive and dependent tissue * Prostate cancer cells retain this sensitivity and dependency – androgens are a key driver of prostate cancer growth. * Therefore, this can be used as an inherent vulnerability that can be exploited for treatment. * Switch off AR signalling, switch off the the cancer growth. * AR targeting is the “Achilles Heel” of prostate cancer. * ‘Androgen deprivation therapy’

Answer 128

Bone thinning-Osteoporosis Erectile dysfunction Fatigue Growth of breast tissue Heart disease Hot flashes Loss of sex drive Loss of muscle mass Dementia & Alzheimers Disease Weight gain

Answer 129

GnRH agonists and antagonists – inhibit testes production Inhibition of Tes conversion to DHT Inhibition of cholesterol conversion to Tes Inhibition of testosterone binding to receptor: Androgen antagonists

Answer 130

Endometrial changes reach their maximum about 7 days after ovulation. The implantation window 6 – 10 days after the LH spike. Pre-decidualizaton 9 to 10 days after ovulation decidual cells cover surface of uterus. Decidualization if pregnancy occurs, decidual cells (modified become filled with lipids and glycogen. Decidua becomes maternal part of the placenta. Glandular secretions of endometrium contains growth factors, adhesion molecules, nutrients, vitamins, matrix proteins and hormones.

Answer 131

Decidual cells on surface of endometrium become filled with lipids and glycogen- becomes maternal part of the placenta. The syncytiotrophoblast results from cell fusion (forms a multi-nucleated cytoplasmic mass) and invades the endometrium. Chorionic gonadotropin is an autocrine growth factor for the blastocyst.

Answer 132

**Implanting day 7-8** **Syncytiotrophoblast erodes the endometrium**. Cells of the embryonic disc form epiblast and hypoblast. **Epiblast** develops fluid filled amniotic cavity. **12-day blastocyst** Implantation complete as **extraembryonic mesoderm forms discrete layer** beneath cytotrophoblast. **16-day embryo** **Cytotrophoblast and associated mesoderm have become the chorion** and chorionic villi are extending. Lacunae filled with maternal blood mingle with villi.

Answer 133

Human chorionic gonadotrophin (hCG) secreted by the syncytiotrophoblast increases rapidly and is basis of pregnancy test. hCG **prevents the death of the corpus luteum** so the endometrium is not shed.

Answer 134

Serum hCG maximal by 9 – 11 weeks. Estrogen and progesterone continue to rise as corpus luteum still produces steroids

Answer 135

**Progesterone** * Synthesised directly from cholesterol * Decidualization (CL) * Smooth muscle relaxation – uterine quiescence * Mineralocorticoid effect – cardiovascular changes * Breast development (glands and stroma) **Estrogens - Estradiol (E2), Estriol (E3)** * Development of uterine hypertrophy * Metabolic changes (insulin resistance) * Cardiovascular changes * Increased clotting factor production * Breast development (glands and stroma)

Answer 136

* About 2.0 kg in total in the first 20 weeks * Then approximately 0.5 kg per week until full term at 40 weeks * A total of 9 -13 kg during the pregnancy. * Failure to gain or sudden change requires investigation. * Constant weight monitoring can cause anxiety.

Answer 137

* Rises by: * 350 kcal/day mid gestation * 250 kcal/day late gestation * (75% foetus and uterus; 25% respiration) * 9 calories = 1g fat, therefore 40g fat for 350kcal * Glucose increases in the maternal circulation in order to cross the placenta.

Answer 138

1. Maternal Store (increased pancreatic cells and insulin) 2. Foetal Store (Placental lactogen) 3. Transfer to foetus

Answer 139

**Estrogen and progesterone** when high acy as mineralcorticoid, retain sodium from kidney to increase blood volume **RAAS - placental renin production.** Estrogen upregulates angiotensinogen synthesis by liver leading to increased angiotensin II and aldosterone. Despite higher ANGII women resistant to AT2 receptor mediated vasoconstriction because progesterone decreases vasosensitivity. **Connective tissue and ligaments** take on water and become a bit softer. **Resetting osmostat** decreased thirst threshold. Decrease in oncotic pressure (albumin). **Up to 8.5 litres total water gain**

Answer 140

* Increased efficiency of iron absorption from gut. * Circulating volume increases from 4.5 to 6.0 litres. * Haemodilution - apparent anaemia as concentration of Hb falls. * Increase in white cells and clotting factors, blood becomes hypercoagulable. * Increased fibrinogen for placental separation, but increased risk of thrombosis.

Answer 141

**Expanding uterus** * pushes heart * changes ECG and heart sounds **Peripheral vasodilation** * mediated by endothelium dependent factors such as nitric oxide synthesis upregulated by E2 * 20-30% fall in TPR so CO increases... **Increased cardiac output** * increased heart rate (8-10bpm) but primarily stroke volume * begins as early as 3 weeks to max 40% at 28 weeks * BP decreases in 1st 2 trimesters * Extra work exacerbates pre-existing conditions, eg aortic valve defects, pulmonary hypertension. **Increased cardiac output and vasodilation by steroids.** * Reduced peripheral resistance * Increased flow to: - Uterus - Placenta - Muscle - Kidney - Skin * Neoangiogenesis, including extra capillaries in skin (spider naevi) to assist heat loss. **Pregnancy characterised by low pressure and high blood volume.**

Answer 142

Folic Acid supplementation

Answer 143

**CRH released into maternal and foetal circulation by placenta.** Increases cortisol (positive feedback) and stimulates adrenocorticotrophic hormone (ACTH) & so DHEA in foetal HPA axis **DHEA is aromatized into estrogen by the placenta**. Increasing E:P ratio snd stimulating prostaglandins which activate blood flow, uterine contractions & cervical ripening.

Answer 144

Increased production of thyroid hormone to meet increased metabolic demand of pregnancy leads to **a risk of gestational thyrotoxicosis** **hCG may act on TSH receptor.** Suppressed TSH and high serum T4 may indicate gestational thyrotoxicosis.

Answer 145

* **Primary function is to retain the pregnancy** * **Increase in vascularity** * **Tissue softens from 8 weeks** * changes in connective tissue * begins gradual preparation for expansion * **Proliferation of glands** * mucosal layer becomes half of mass * great increase in mucus production * Protective ie anti-infective

Answer 146

**Prolactin** * produced by myometrium and placenta * in response to high estrogen and progesterone. * However, **estrogen and progesterone inhibit** the stimulatory effects of prolactin on **milk** production. * The **abrupt drop in estrogen and progesterone** levels following placental delivery allows **high levels of prolactin to induce lactation.** * After birth, sucking activates nipple mechanoreceptors signaling the hypothalamus and causing anterior pituitary prolactin secretion.

Answer 147

**Oxytocin** * Stretching of uterus and cervix during childbirth causes release of oxytocin * which helps with the birth and emotional bonding with the baby. * Suckling stimulus triggers the release of **oxytocin from the posterior pituitary** gland, which triggers **milk ejection.** *

Answer 148

**Gestational Diabetes Mellitus (GDM):** Impaired glucose tolerance between 24-28 weeks of gestation. **Preeclampsia:** high blood pressure signs of damage to other organ systems, usually developing sfter 20 weeks of gestation. **Hyperemesis Gravidarum:** Severe nausea and vomiting can lead to dehydration, electrolyte imbalances, and weight loss. **Placenta Previa:** placenta partially or completely covers the cervix, leading to bleeding, especially during the third trimester. **Deep Vein Thrombosis (DVT):** can be more common during pregnancy due to increased blood coagulability and decreased venous return.

Answer 149

Outer longitudinal fibres Middle figure of eight shaped fibres Inner circular fibres All smooth muscle When contraction causes increases in uterine pressure forcing contents to cervix Acts as a natural ligature to prevent blood loss

Answer 150

* Myometrium is spontaneously active – myogenic * Spontaneous contractions are highly sensitive to neurotransmitters, hormones (oestrogen and progesterone) * Progesterone – Inhibits contraction * Oestrogen, Oxytocin, Prostaglandins – Increases contraction * **Non-pregnant uterus: **Weak contractions early in cycle, * Strong contractions during menstruation (low progesterone, high PGs) * **Pregnant uterus: **Weak and uncoordinated in early pregnancy (high progesterone), Strong and co-ordinated at labour (high oestrogen/oxytocin/prostaglandins) * ***Remember: Increased Oestrogen/Progesterone ratio during labour***

Answer 151

* Myometrium is spontaneously active – myogenic * Myometrium is innervated by **sympathetic** nerves (not parasympathetic) * Myometrium contains both α and β receptors * Stimulation of α produces contraction * Stimulation of β2 produces relaxation

Answer 152

* Myometrium contain pacemaker cells - I**nterstitial Cells of Cajal (ICCs)**, which initiate and coordinate contractions * ICC electrical conduction pass via gap junctions from sm muscle to sm muscle * Uterus acts as syncytium * Oestrogen and oxytocin increases gap junction expression in labour

Answer 153

**Slow waves:** slow depolarisations produced by pacemaker cells (**ICCs**) **Electrical activity spreads via gap junctions to SMCs** Activates action potentials in SMCs - upstroke of APs are carried by Ca2+ through VGCCs which leads to increase in [Ca2+]i AND contraction **Slow waves/SMCs are modulated by neurotransmitters /hormones**

Answer 154

* PGE2 (dilate) and PGF2α (constrict) synthesised in myo and endo metrium * Can increase myometrium contractions * NSAIDS can help dysmenorrhoea and menorrhagia * Act to coordiante increased freq/force contractions, gap junctions, soften cervix and increased oxytocin * PG effective in early / middle pregnancy * Induce labour preterm * Induce abortion, postpatum bleeding, softe ncervix * BUT system vasodilatation and CVS collapse, PG hypertonus fetal distress

Answer 155

* ergot fungus from rye and cereal * ergotism, gangrene, convulsion, abortion * powerful prolonged uterine contraction when myometrium relaxed * Stimulates α adrenoreceptors, ?5-HT * Used in post partum bleeding

Answer 156

* Salbutamol * Relax uterine contractions by a direct action on the myometrium * Used to reduce strength of contractions in premature labour * May occur as a side effect of drugs used in asthma

Answer 157

nifedipine (used in hypertension) or magnesium sulfate

Answer 158

* NSAIDs * (low prostaglandin) * why NSAIDS are useful to treat dysmenorrhoea and menorrhagia * but may cause fetal renal dysfunction (reduce renal blood flow

Answer 159

* These drugs may be used in premature labour * Important: Delay delivery by 48 hrs, so Mother can be transferred to specialist unit, and given antenatal corticosteroids * Aid foetal lung maturation and increase survival

Answer 160

* These drugs may be used in premature labour * Important: Delay delivery by 48 hrs, so Mother can be transferred to specialist unit, and given antenatal corticosteroids * Aid foetal lung maturation and increase survival

Answer 161

Primary germ cells or spermatogonia on the basement membrane Walls of tubule made up of tall columnar endothelial cells Sertoli cells. Tight junctions between these form Adluminal compartment. Allows specific enclosed environment for spermatogenesis which is filled with secretions from Sertoli cells. Spaces between the tubules are filled with blood and lymphatic vessels, Leydig cells and interstitial fluid.

Answer 162

Leydig cells contain LH receptors and primarily convert cholesterol into androgens. Intra- testicular testosterone levels are 100x those in plasma. Androgens cross over to and stimulate Sertoli cell function and thereby control spermatogenesis. Sertoli cells contain FSH receptors and converts androgens to oestrogen. FSH establishes a quantitatively normal Sertoli cell population, whereas androgen initiates and maintains sperm production.

Answer 163

Seminal Vesicles Secretions comprise 50-70% of the ejaculate. Contains proteins, enzymes, fructose, mucus, vitamin C and prostaglandins. High fructose concentrations provide energy source. High pH protects against acidic environment in vagina. Prostate Secretes milky or white fluid roughly 30% of the seminal fluid. Protein content is less than 1% and includes proteolytic enzymes, prostatic acid phosphatase and prostate-specific antigen which are involved in liquefaction. High zinc concentration 500–1,000 times that in the blood is antibacterial.

Answer 164

No SRY Wollfian lost as no testosterone Mullerian continue to development External female genitalia as no 5a Reductase.

Answer 165

SRY Testis -> Leydig -? Testosterone AMH production inhibits mullerian. Wollfian develop into epididymus External Male genitalia as 5a reductase present so DHT occurs.

Repro Flashcards

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