Female Reproductive System - Overview
- Ovaries are the main reproductive organs and house oocytes (immature eggs)
- The ovaries contain follicles in different stages of development
- Ovulation occurs when a follicle bursts, releasing an oocyte into the peritoneal cavity
- Post-ovulation, the follicle transforms into a corpus luteum
- If fertilization doesn't occur, the corpus luteum turns into scar tissue
- If fertilization occurs, the corpus luteum continues secreting progesterone and a bit of estrogen to support early pregnancy
- Fallopian tubes are funnel-shaped with fimbriae located near the ovaries
- Fertilization usually occurs inside the fallopian tubes
- They move the egg toward the uterus
- The uterus is a thick, muscular organ that hosts a fertilized egg
- The uterus has 3 layers:
- Perimetrium: outer layer
- Myometrium: smooth muscle that contracts during labor
- Endometrium: inner lining with 2 layers
- Functional layer sheds during menstruation
- Basal layer: remains and regenerates
- The cervix is the neck of the uterus and opens into the vagina
- The cervix secretes mucus, which acts as a barrier to pathogens and sperm when not ovulating
- The vagina is a muscular canal that connects the uterus to the outside world
- The vagina serves as a passage for menstrual blood, semen, and a baby during childbirth
Ovarian and Uterine Cycles
- The ovarian cycle involves changes in the ovaries, including the follicular, ovulation, and luteal phases
- During the follicular phase (days 1-14), FSH stimulates follicle development, and one follicle becomes dominant, leading to increased estrogen
- Ovulation happens around day 14 and involves an LH surge that causes follicle rupture and egg release
- During the luteal phase (days 15-28), the corpus luteum forms and produces progesterone
- If no pregnancy occurs, the corpus luteum breaks down, causing a hormone drop and the start of menstruation
- The uterine cycle involves changes in the endometrial lining which includes menstrual, proliferative, and secretory phases
- During the menstrual phase (days 1-5), the functional layer of the endometrium is shed
- During the proliferative phase (days 6-14), estrogen helps rebuild the lining
- During the secretory phase (days 15-28), progesterone prepares the lining for implantation
- If there is no pregnancy from the secretory phase, the lining breaks down, and the cycle repeats
Key Hormones of the Menstrual Cycle
- FSH (Follicle-Stimulating Hormone) stimulates follicle growth in the ovary
- LH (Luteinizing Hormone) triggers ovulation and supports corpus luteum formation
- Estrogen is dominant in the follicular phase and thickens the endometrium, and peaks just before ovulation helping the LH surge
Progesterone
- Dominant in the luteal phase
- Prepares endometrium for fertilized egg
- If pregnancy does not occur, progesterone levels drop, leading to menstruation
Follicular Phase (Days 1-14)
- Hormones: FSH increases, leading to follicle maturation and increased estrogen
- Ovaries: Follicles develop
- Uterus: Endometrium rebuilds during the proliferative phase
- Cervical mucus: Becomes thin, watery, and fertile
- Temperature: Low-normal
Ovulation (Around Day 14)
- Hormones: LH surge triggered by high estrogen levels
- Ovaries: Egg is released
- Uterus: Lining is ready
- Cervical mucus: Stretchy and egg-white-like (spinnbarkeit)
- Temperature: Slight drop, then sharp rise after
Luteal Phase (Days 15-28)
- Hormones: Corpus luteum produces increased progesterone and some estrogen
- Ovaries: No more follicle activity
- Uterus: Secretory phase which thickens lining and secretes nutrients
- Cervical mucus: Thick and sticky
- Temperature: Stays elevated until next period or longer during pregnancy
Incidence and Consequences of Unintended Pregnancy
- Approximately 6 million pregnancies occur per year in the U.S
- Around 50% of pregnancies are unintended, and about half of those end in abortion
- 11% of pregnancies occur when people use no contraception
- 89% of unintended pregnancies occur due to inconsistent/imperfect contraceptive use or contraceptive failure
Consequences for the Fetus/Child
- Decreased Prenatal care
- Increased Exposure to harmful substances
- Decreased Birth weight (<5.5 lbs)
- Decreased likelihood of Breastfeeding
- Increased Risk of death in the first year, abuse, or developmental issues
Consequences for Parents
- Increased Maternal depression
- Increased Risk of abuse toward mother
- Increased Breakup/divorce rates
Consequences for the Healthcare System
- One birth = $$$
- In 2008, $1.9B spent on family planning saved $7B in Medicaid costs
- Every $1 spent resulted in $3.74 saved
- In 2006, family planning prevented 1.94M pregnancies and 810K abortions
Nonprescription STI and Pregnancy Prevention Methods
- Male Condoms:
- Protect against STIs and pregnancy
- Materials: Latex (standard), synthetic (for allergies), or natural membrane (pregnancy prevention ONLY)
- ADRs: ↓ sensitivity, latex allergy
- Tip: leave ½ inch space at the tip and withdraw right after ejaculation
- Internal (female) condoms:
- Latex-free
- Can be inserted up to 8 hours before sex
- Covers vulva + vaginal canal for more protection
- Cons: More expensive and can be noisy and cause irritation
- Spermicides (nonoxynol-9, etc):
- Kills sperm and forms a barrier
- Can cause increased genital irritation with frequent use and does not prevent STIs
- Contraceptive Sponge:
- Contains spermicide
- Insert before sex and leave in ≥6 hrs after
- Should not be used during period or less than 6 weeks postpartum
- increased Risk of toxic shock
- Diaphragm & Cervical Cap:
- Covers cervix with spermicide
- Must be fitted which requires prescription
- Leave in 6-24 hours for diaphragm and 6-48 hours for cervical cap
- Doesn't protect against STIs
- Phexxi:
- Vaginal pH modulator that requires a prescription
- Use before each sex act
- Should not be used if you have UTIs or use vaginal rings
Counseling Points for Non-Pharmacologic Contraceptive Methods
- No method (besides abstinence) is 100% effective
- Know the difference between perfect use vs. typical use
- Always check expiration dates, storage conditions, and proper technique
- Use backup if condom breaks such as spermicidal foam/jelly ASAP
- Recommend dual protection with barrier + FAB or barrier + spermicide for higher effectiveness
- Educate about STI protection limits since only condoms protect
- Know when NOT to use certain methods for example, a sponge + menstruation = NOPE
- Provide non-judgmental, private counseling
Fertility Awareness-Based (FAB) Methods of Contraception
- Calendar Method: Tracks cycle lengths with a perfect use failure rate of 3% and a typical use failure rate of 15-19%, and only works if cycles are regular
- Standard Days: Avoid sex on days 8-19, has a perfect use failure rate of ~5% and a typical use failure rate of 12%, and only for 26-32 day cycles
- Cervical Mucus (Billings): Observes mucus consistency, has a perfect use failure rate of ~3% and a typical use failure rate of 23%, and raw egg white mucus indicates fertility
- TwoDay Method: Determines that if any secretions today/yesterday the user is fertile, has a perfect use failure rate of ~4% and a typical use failure rate of ~14%, and is easy to use
- Symptothermal: Combines mucus observation + basal body temperature, has a perfect use failure rate of 0.4% and a typical use failure rate of 2%, and needs daily temperature charting
- LAM: Exclusive breastfeeding + less than 6 months + no menses, has a perfect use failure rate of ~1-2% and a typical use failure rate of 2-6%, and is not reliable with formula/supplementing
- Withdrawal (Coitus Interruptus): Pull out before ejaculation, has a perfect use failure rate of 4% and a typical use failure rate of 22%, and does not protect against STIs
Hormonal Contraceptives - Mechanism of Action
- Suppress ovulation by inhibiting FSH & LH via negative feedback
- Thicken cervical mucus to block sperm entry
- Leads to Altered endometrium which is hostile to implantation
Benefits
- Regulates menses
- Decreases cramps
- Decreases blood loss
- Decreases anemia
- Decreases ovarian & endometrial cancer risk
- May help acne, migraines, PMDD, etc
Adverse Events
- Common (early): nausea, bloating, spotting which usually resolves by cycle 3
- Serious: ACHES = D/C. immediately
- A= Abdominal pain
- C = Chest pain
- H = Headaches (severe)
- E = Eye issues (vision changes)
- S = Severe leg pain
Drug Interactions:
- Rifampin: confirmed ↓ efficacy so use backup x 7-28 days
- Antiepileptics: phenytoin, carbamazepine, phenobarbital = trouble
- Lamotrigine: levels drop for seizure risk
Oral Contraceptives - Types and Considerations
- COCs (Combined Oral Contraceptives):
- Ideal for: Healthy, <35yo, no major risk factors
- Not ideal for: Smokers >35, HTN w/ complications, DVT/PE hx
- Pearls: Can start anytime with backup for >5 days after menses
- POPs (Progestin-Only Pills):
- Ideal for: Breastfeeding, migraine w/ aura, HTN, high VTE risk
- Not ideal for: Forgetful folks (strict timing needed)
- Pearls: Backup if late >3 hours
- Patch (Xulane):
- Ideal for: Non-obese, prefers weekly dosing
- Not ideal for: >90 kg = ↓ efficacy
- Pearls: Increased estrogen exposure (60%) leading to an increased VTE risk
- Ring (NuvaRing):
- Ideal for: Wants monthly option
- Not ideal for: If ring falls out often
- Pearls: Leave in for 3 weeks, and remove for 1 week
- Injection (Depo):
- Ideal for: Poor adherence, breastfeeding, seizure pts
- Not ideal for: Quick return to fertility
- Pearls: Weight gain and decreased bone density
- Implant (Nexplanon):
- Ideal for: Long-term, low maintenance
- Not ideal for: Irregular bleeding
- Pearls: Effective for 3 years
- IUD (LNG or Copper):
- Ideal for: Most effective and forget-proof
- Not ideal for: Wants STI protection or has PID
- Pearls: Fertility returns in ~30 days after removal
Oral Contraceptives - EE Content, Phases, and Progestins
- EE Content: High: >35 mcg, Low: 30-35 mcg, Ultra-low: <30 mcg
- Phases:
- Monophasic = a consistent dose throughout most flexible
- Triphasic = hormone dose varies by week
- Progestins to consider:
- Norgestimate is less androgenic
- Drospirenone is anti-androgenic for acne, but increases the VTE risk
Oral Contraceptives - Additional Considerations
- Levonorgestrel is the gold standard and has moderate androgenic activity
- Extended cycle: fewer less periods/year
- Continuous cycle: no placebo week eliminates menstruation altogether
- Use in dysmenorrhea, PMDD, migraines, and endometriosis
Starting options for Hormonal Contraceptives:
- Quick start anytime, use backup for the first 7 days
- Sunday start start Sunday after bleeding begins
- Day 1 start: Start on the 1st day of menses for immediate contraception.
Missed Doses (COCs):
- 1 pill: take ASAP/ no backup required
2 pills: take the most recent, discard the remainder/ use backup for 7 days.
- If this occurs in the last active week, skip placebo and start new pack
ADRs:
- BTB (breakthrough bleeding)= wait out three cycles
- Nausea: decrease estrogen dose
- Mood Swings? Rule out depression first
Factors to consider when prescribing hormonal contraceptives:
- Age, smoking, VTE= avoid estrogen
- Adherence Problems= use a shot, IUD, or implant
- Breastfeeding= POP, IUD, or injection
- Acne= drospirenone, or low-androgen progestin
Contraceptive changes based on ADRs:
- BTB (late cycle) = increase progestin dose.
- BTB( early cycle)= increase Estrogen
- Nausea = decrease estrogen.
- Acne/ Hirsutism= decreased androgenin progestin
Emergency Contraception
- Plan B (levonorgestrel) 1.5 mg x 1, up to 72 hours (up to 5 days) OTC, Less effective if the patient has a BMI >30
- Ulipristal (Ella) 30 mg x1 within 5 days, requires a Rx -Hold high-dose contraceptive administration x 5 days post EC use.
- Copper IUD, insert within / less than 5 days, it's the most effective and also a solid long-term option!
- Yupze (High dose combo, <72 hrs) More nausea, less preferred.
Abortifacients
- Mifepristone + Misoprostol!
- Blocks progesterone leading to the uterus shedding its lining
- Used up to 10 weeks gestation
- Side effects= cramping heavy bleeding + nausea
- Illegal in Texas
Hormonal Contraception: Goal is to Suppress Ovulation.
- Progestin ( + or - estrogen )--> inhibits GNRH, FSH and LH
- Progestin Action= thickens cervical mucus, prevents implantation and decreases mobility of the fallopian tubes= no menstruation!
- If you have Progestin Action decreases FSH, which decreases follicle development
Progestins ( synthetic form of progesterone)= Longer lasting than natural
- Estrogen has a T1/2 of ~36 h--> metabolized by the liver via CYP enzymes. Then it becomes an active via enterohepatic recirculation
Adverse Effects:
- Irregular Bleeding with minipills
- Breast Tenderness/ Nausea
- Higher VTE risk wiht estrogen!
- Lower bone density with injectable depo prevention!
Pharmacodynamics of Combination Oral Contraceptives (COCs):
- Combo of estrogen and progestin
- Block Ovulation by suppressing GnrH/ FSH and LH.
- Estrogen stabilizes the endometrium while Progestin thickens the mucus
Adverse effects:
- Higher vte risk (mostly in smokers/ elderly)
- Nausea + Mood Swings
- Breakthrough Bleeding
Progestin-Only Pills:
- MOA: thickens the cervical mucus, there is weak suppression of ovulation
- Strict daily timing, very short 1/2 life- easy to missproection when timing is delayed
Adverse Effects:
- Irregular/ Unpredictable Bleeding
- Slightly Less effective
Non-oral Contraceptives:
- Depo-provera = progestin/ injection /every month/ bone density depletion
Emergency Contraception: Progestins
- Levonorgesteral ( 1x of 1.5mg or 2 doses of 0.75mg) take within 72 hours
- Blocks/delays Ovulation and does Not disrupt existing pregnancy.
SRPMs- Ulipristal =Single dose of 30mg: up to 120 hours- but Rx only
Anti -Progestin
- Mifepristone
- Competitive PR Antagonist, used to terminate early pregnancy / Used for Cushings
- Blocks Progesterone.
Causes Uterine Contractions ---> treat with Misoprostol
Estrogen
- Binds ER alpha and beta. Affects gene expression. Stimulates growth & improves lipids
- Give Orally- metabolized via the liver excreted in the bile
- Can increase endometrial cancer unless paired with progestin. Can increase breast cancer, VTE, and gall bladder issues.
SERMS Selective Estrogen Receptor Modulators:
- Mixed Agonist/ Antagonist depending on the tissue
- Ex: Tamoxifen- Antagonist in the breast but an agonist in the uterus
SE = hot flashes/ DVT risk/ endometrial Thickenening
Progestins
- Binds to Progesterone receptors - effects the endometrium & blocks ovulation
- Can administer in many ways synthetics are much better with pregnancy
Androgens
- Increase Muscle and Bone Mass
- Side effects= decrease testicular size and sperm production- Acne and Aggression
GNRH Receptor
- Analgoues!
- Inital surge LH and FSH with long term use pituitary decreases and suppresses Estradiol and Testosterone
- Treats Endo & Cancer - administered via SQ/IM Implant
Analgoues w/ GNRH receptors
- Side fx: Bone Loss/ Hot Flashes
- Elagolix direct agonist and receptor blocker , decreasing LH and FSH which decreases estrogen and progesterin
Armoatase Inhibitors
- Anastrozole and Leztrozole: Block aromatase , so you cant synthesise hormones --> so decrease Andorgens + Estrogens
- Use it to treat Breast Cancer
- AE - Hot Flashes
Menstrual Disorders - Amenorrhea
- No menses for >90 days causes are anorexias, PCOSs, Thyroid Issues
- Signs/ symptoms is amenorrhea and no fertility and vaginal dryness
- Test: HCG, FSH, Prolactin, Pelvic US!
Heavy Menstrual Bleeding
- Is defined when there is >80ml per cycle ore 7 or more days causing fatigue
- Coagulation or Endo issues, Treat with CBC!
AB with Ovulation
- Caused when there is hyperplasia can occur wth PCOS, thyroid issues
- Check Testetorone/ Glucose and TSH levels!
Dysmenorrhea
- Painful 8 to 72 hours wthin menses/ cramps/ nausea!
- Could be Prostagladin related or secondary related to Fibroids/ anatomical blockage
PMS/PMDD
- PMS = 80% of women!PMDD= 9% of women!
- All the PMS signs + More!
MOA Meds Used to Manage
- Amoorhoea/ Lestrozone and Dopamine to stimulate ovulation!
- HMB= Tranexemic Acid to reduce bleeding! -or- IUD!
Treatment Safety
- CHC = clot for AUB
- Tranexemic= Cautious of clotting issues
Patient -Centeread Care
- Check for: the Cause (PCOS v Atoneriua)
- Patients Goals + Comobitidies.
Plan= Anoohea with a PCOS
- Prescribe Lestrozone
- Check Glucose level
Menses with more heavy bleed
- Use IUD + Back with tranaxemic Acid
- Severe Mood Issue
- Fluoxetine !
- or
- -add a CHC in drospirenone if needed!!
Hormon Replacement Therapy
- MEnoupause = no Menstruation for more than a year ~Age51
- This process is triggered with a decrease in Estogen Production
- Trigger- Surgival- radiation- kemo!
Goals
- The goal of the patient is to reduce symptoms with hot flashes and improve mood!
- Non-Pharm--> fans and layered clothing!
Pharm
- Is Estogen/ Progestin.
- If Uterus---> estopgen + progestin!
- -else-Give Estrogen Solos!
- Locak Estrogen= Creams .
MOA
- Estrogen to reduces vasomotor GSM
- Give oral
Absolute Contradictions
- Breast cnacer
- CHC-CVA Liver Disease/Pregnancy
Assesses Risk/Benefit
- Improves mood , gives bone Protection etc decreases the risk of VTE stroke
- Take it if your Younger than 80 but less than 10 years post- menoupause - if not Transemdla- which decreased VTE risk!
Gender Afrriming Therapy
- Hormoanl --> Estridol and Testoreone
- Note, you can allter- Non- Pharm options/ Chest binding
- Social Support System
Goals
PAtient MUST BE well documented/ show capacity!-For Estridol= it binds receptors= so feminize--Side effects are==> VTE/ gall Stiomes - Liver enzymes - can monitor Estrodial and tester torone levels
- Anti-Testrone = is Sprioloactrone
Decrese tester one - side effect- hyperkalmic, to monitor- Psa if indicated
Also, GnrH Agalogues
Tranmsc Patients
Give Tester toner
- -Side Effects ---> acne , alopecia
monitor for: testosterone level / LFT's/ Lipids / weight
Goals
- Align theraputic goals+ lab value, check and do screening and therapy and adjust based on lab valus ect.Check for Labs --> VTEand for Steroids-> Hyperkelemia!
