Chapter 23 - Reproductive

FSH

stimulates follicle development in early days of cycle

LH

large spike about 1-2 days before ovulation

Estrogen

increases as follicle develops, then again mid-luteal phase

Progesterone

very low until just before ovulation, then large increase during luteal phase

Which hormones peak just before ovulation

- LH

- FSH

- Estrogen

Which hormones peak after ovulation in the luteal phase?

- estrogen

- progesterone

How does LH surge trigger ovulation?

- 1. high levels of estrogen from the developing follicle causes postive feedback which increases GnRH and LH

- 2. increased LH causes enzymes and prostaglandins produced to break down membranes of follicle and ovary to release the egg in ovulation

Negative Feedback during Luteal Phase

estrogen and progesterone secreted by the corpus luteum inhibit FSH and LH secretion which prevents another ovulation from occuring

Corpus Luteum

empty ovarian follicle that secretes progesterone after release of the egg cell and degenerates within 14 days, removing the inhibition of FSH and LH unless fertilization happens

Endometrium

lining of the uterus

Effect of Estrogen

causes proliferation during ovarian follicular phase

Combination of Epinephrine & Progesterone on Endometrium

during luteal phase it makes endometrium favorable to implantation of developing embryo

Effect of Progesterone

inhibits uterine contraction during luteal phase and pregnancy & causes thicker cervical mucus

Removal of progesterone =

contraction/dysmenorrhea (menstrual cramps)

Egg is viable for _____ days

1-2

Sperm are viable for _____ days

4-6

Window for conception

5 days before to 1 day after ovulation

Contraceptives

work prior to implantation to prevent pregnancy & suppresses ovulation

Emergency Contraceptives

taken after unprotected intercourse or barrier method failure & suppresses ovulation

Abortifacients

terminate existing pregnancy post-implantation

Combination Hormonal Contraception

consists of estrogen/progestin combination which are metabolized slowly

What estrogen is in the pill?

ethinyl estradiol

Primary Mechanism of the pill

progestrin is a negative feedback inhibitor of the FSH/LH surge and estrogen makes hypothalamus more sensitive to progestin so ovulation never occurs

Traditional dosing

21 days active, 7 days placebo

Monophasic

same hormone dose throughout

Triphasic

dosage varies at different points in the cycle

Alternate delivary systems

transdermal patch or vaginal ring

Secondary contraceptive effects

- making uterus inhospitable to implantation

- thickening of cervical mucus

- inhibiting transport in fallopian tube

Non-Contraceptive Uses of Hormonal Preparations

- irregular or heavy menstrual bleeding

- severe menstrual cramps

- PMDD

- acne

- menstrual migraines

- HRT

- management of endometriosis

- PCOS

- reduction in cancer risk

Adverse effects of combination pills

- breakthrough bleeding

- headache

- nausea

- breast tenderness

- increased skin pigmentation

- weight gain

- thromboembolism risk increased

- increased risk of gallstones

- migraine

Drug interactions with combo pills

- antibiotics (rifampin)

- some anti-seizure medications

- St. John's Wort

Enterohepatic cycling

estrogens are metabolized by the liver and are secreted into the small entestine where bacteria can convert it back to the active form & it is reabsorbed back into the body

Progestin-Only Contraception

avoids adverse effects that occur with estrogen in the combi pills such as clotting, gallstones, & mirgraine but it is somewhat less effective at suppressing ovulation

Types of Progestin-Only

- pill form

- depot injection

Pill form (minipill)

slightly higher failure rate so regular dosing is more important compared to combo pills

Depot Injection

must get shot every 12 weeks but otherwise low maintenance and very effective

Side effects of progestin-only

related to androgenic effects of progestin incluidng acne, hirsutism, and mood changes

Long-acting reversible contraception

the most effective contraception and is progestin-only with several delivery methods

Different delivery methods:

- subdermal

- intrauterine device

Subdermal

nexplanon; device for the arm

Intrauterine devices

- mirena

- skyla

Advantages of LARC

- little chance of human error

- can be left in place for 3+ years

Adverse effects of LARC

- irregular/frequent mestruation

- amenorrhea after several months

- unpleasant insertion/removal procedures

Emergency contraception drugs

- levonorgestrel

- ulipristal

Levonogestrel

- one or two doses

- available OTC

- must be taken within 72 hours of intercourse

Mechanism of levonogestrel

suppression of ovulation & is ineffective after the LH surge has begun

Effectiveness of levonogestrel

75-90% effective

Ulipristal

- single dose taken within 120 hours

- prescription only

Ulipristal Mechanism

selective progesterone receptor modulator that blocks LH surge if it has not already begun & prevents follicular rupture

Effectiveness of Ulipristal

85% effective

Copper IUD

this IUD can be used as emergency contraception or long-term but must be inserted within 5 days & is the msot effective emergency contraception

Copper IUD mechanism

copper ions are released and are toxic to serm; also exhibits foreign body effect where endometrial inflammatory changes inhibit implantation

How long can copper IUD be left?

up to 12 years; it lacks hormonal methods but still works as a contraceptive

Main disadvantages of copper IUD

menstruation may be irregular, heavier and/or longer

Medication Abortion

works after implantation and is approved for up to 70 days gestation

Preferred Regimen of Medication Abortion

- mifepristone

- misoprostol

Mifepristone

selective progesterone receptor modulator that blocks endometrial progesterone receptors, resulting in degredation

Misoprostol

prostaglandin agonist that stimulates uterine contraction and can be used alone if mifepristone is not available

Safety of Abortion

- often produces bleeding and cramping much heavier than normal menses

- side effects of nausea/vomiting/diarrhea/headache/dizziness/fever/chills

Efficacy of Abortion

typically 95-98% effective at ending pregnancy without any further procedures necessary

Erection

occurs when aterioles dilate and allow blood flow into corpus cavernosa/spongiosum & works as a spinal reflex but also heavily influenced by the brain

Erectile dysfunction

often is a symptom of another medical problem such as cardivascular or endocrine issues

What type of drugs are used for erectile dysfunction?

phosphodiesterase type 5 inhibitors

What are the phosphodiesterase type 5 inhibitor drugs?

- sildenafil

- tadalafil

PDE5 Inhibitor Characteristics

- take 60 min before sexual activity

- 60-80% effective

Which drug lasts longest?

tadalafil (36 hr)

Adverse effects of PDE5

- headaches

- facial flushing

- visual effects

PDE5 Contraindications

- never use with nitrates

- alpha-blockers for BPH may also cause hypotension when used together but generally considered safe with other antihypertensives

Steps of Action

- 1. sensory stimulation and/or brain inputs activate non-adrenergic & non-cholinergic neurons

- 2. nitric oxide released from NANC neurons activates guanylyl cyclase which produces cGMP

- 3. cGMP causes relaxation of arteriole smooth muscle, allowing blood to flow into corpus cavernosum

- 4. process is terminated by PDE5 breaking down cGMP, but PDE5 inhibitors prevent the breakdown of cGMP which makes erection easier to achieve and maintain