Oral Contraceptives, HRT and SERMS Flashcards
Oral Contraceptive Pill (OCP):
-Synthetic combination of Progesterone and Estrogen.
•Combination of Estrogen and progestin through 21 days- 7 days placebo
•When the combined pill is withdrawn, normal bleeding occurs, mimicking normal menstruation (but during the cycle there is NO ovulation)- pregnancy is avoided.
–>Blocks ovulation by keeping FSH/ LH levels low.
-Administration of progesterone changes the endometrium lining, ensuring it stays thick so sperm stays impermeable to the wall.
-Keep FSH/ LH levels low throughout a women’s cycle.
True or False: Estradiol undergoes first pass metabolism in the liver.
True
Ethinylestradiol (EE2) or Mestranol
Synthetic Estrogen
Levonorgestrel, Norethynodrel, Norgestrel
Synthetic Progesterone
Adverse Effects and Contraindications of OCP:
- Estrogen Beneficial Effect- Includes plasma HDL levels and decreases bone resorption caused by PTH
- Estrogen’s undesirable effects: Includes nausea, vomiting, mastalgia (breast pain), edema and skin hyper pigmentation- Chloasma, and increased withdrawal bleeding.
- ->If noticed, decrease the dose of EE2 in the OCP.
- COULD increase coagulation factors (clots/ venous thromboembolism risk)
-Always watch for symptoms or family history of stroke, heart failure, VTE, Peripheral Artery Disease, ect. with OCP
OCP risk of DDI’s?
-OCP have decreased efficacy when taken with antibiotics (reduces efficacy due to increased intestinal excretion by reducing the enterohepatic reabsorption of estrogen.
- Estradiol glucuronide (E2- G) presented in the gut from the liver via bile is broken down by bacterial beta- glucuronidase to free E2, which undergoes enterohepatic circulation.
- ->In the absence of gut microflora following a long term antibiotic regimen, more estradiol is excreted as E2 glucuronide conjugate in the feces, reducing E2 reabsorption resulting in decreased E2 bioavailability.
-Drugs which cause this decrease in efficacy include Carbamazepine, Phenytoin & Rifampin (increase hepatic metabolism of EE2 in OCP)
Transdermal Hormonal Contraceptive Patch:
- Wearing the patch containing estrogen/ progesterone for 3 weeks on and 1 week off.
- Better adherence compared to OCP- presents a higher level of EE2.
Drawbacks:
- Lower efficacy in obese women
- Possibility of increased thromboembolic risk
The Nuva Ring
- Type of Vaginal Ring
- Inserted on the 5th day of the menstrual cycle and releases 15 ug of Ethinyl Estradiol (EE2) and 120 ug of Etonogesterl.
–Give 1 week off and start again on day 5 after menses.
Drawbacks: Sudden expulsion- lowers its efficacy
Progesterone- Only Preparations:
- Parental Administration
- Ideal for women intolerant to estrogen
3 Types:
- Depot Medroxyprogesterone Acetate (DMPA): 150 mg (deep IM administration every 3 months).
- DMPA- given SC (longer duration of action)
- Subdermal Depot Progestin Implant
- Norplant is effective for 6 months
- Nexplanon is 68 mg Etonogesterel (4cm implant placed under the skin, which slowly releases Etonogesterel (60-30ug/ day) over 3 years.
* All are 99% effective.
Drawbacks: Irregular bleeding, vaginitis, lack of menstrual cycle and delayed onset of ovulatory cycle, as well as not having a regular menstrual cycle is worrisome.
Copper IUD:
- Copper wire in the IUD interferes with sperm movement and Nidation (Implantation).
- Requires a health professional to insert (can caused painful periods- dysmenorrhea), increased uterine PG formation, uterine/ pelvic inflammation and allergy to copper are all adverse effects.
- Expulsion is the drawback
- ->Cost= $200 (Safe for up to 5 years)
Progesterone Releasing Plastic IUD (Mirena):
- Superior over Copper- T IUD
- Higher cost ($600-900)- low and sustained Levonorgestrel release serves as an effective contraceptive.
- -Mirena is the drug Trade name
- Efficacy is much better (>99%)
- Drawbacks include expulsion, reduced and irregular menstruation, cramping pain, weight gain, acne and hair growth.
Emergency Contraception/ Plan B:
- Post Coital Progestin
- Taken within 72 hours of coitus
- 1 tablet is a high dose Levonorgesterel
- 1 tablet is an intermediate dose of 1. 1 tablet is a high dose Levonorgestrel followed by another tablet within 12 hours.
- Ulipristal Acetate (a SPRM) -single dose (30mg) tablet within 120 hours of coitus
- -SPERM is a selective progesterone receptor modulator
Ulipristal Acetate:
- -Progestin Antagonist
- -Doesn’t allow for maintenance of the fertilized egg.
- A single dose (30mg) tablet within 120 hours of coitus
- -SPERM is a selective progesterone receptor modulator
Mechanism of Action:
-Both estrogen and progestin together is required for implantation to maintain pregnancy. A very high dose of progestin per se interferes with the process of implantation. With the sudden decrease in progestin, there is withdrawal bleeding and the fertilized egg dislodges.
Mifepristone (RU486):
- Progesterone Antagonist
- dosed at 400-600 mg per day for 4 days with prostaglandin (PGE1 or 15 methyl PGF2alpha)
- Mifepristone is a steroid- acts as a competitive blocker of both progesterone and glucocorticoid.
- Allows for the termination of pregnancy up to 53 days.
- Also useful in the management of Cushing Syndrome (Excess Cortisol) & Endometriosis.
Methotrexate:
- First trimester abortifacient (MTP)
- Cytotoxic agent towards the placenta- given along with uterine stimulants such as Misoprostol- PGE1 analog (600-800 mg) or 15 methyl PGF2alpha administration would stimulate uterine contraction and disrupt the fetus, leading to fetal expulsion.
- -In Canada, Methotrexate & Prostaglandins aren’t used for the termination of pregnancy.
Hormonal Replacement Therapy– Benefits of Ethinyl Estradiol (EE2):
Advantages: Better Sleep, CV protective, reduced osteoporosis, reduced urethritis, vaginal atrophy, as well as reduced hot flashes.
Drawbacks: Susceptible to breast cancer, endometrial cancer, VTE and Stroke
How can we overcome these potential drawbacks of HRT using EE2?
SERMS
- Selective Estrogen Response Modifiers
- Using SERMS instead of Estrogens to overcome the disadvantageous aspects of estrogens
Fulvestant:
- non selective SERM
- A steroidal competitive antagonist at all Estrogen receptors (derivative of estradiol)
- Effective in the early management of estrogen dependent breast carcinoma when Tamoxifen fails.
Tamoxifen*:
- A non-steroidal partial agonist and a SERM
- Blocks estrogen receptors in the breast, and therefore is useful in the early stages of treatment of estrogen- dependent breast carcinoma.
Drawbacks:
- Promotes estrogenic activity in the endometrium and a cause for a risk of endometrial carcinoma.
- Enhances deep vein thrombosis and pulmonary embolism.
- It can enhance clotting factor production like estradiol, although it blocks the estrogen receptors in the breast.
Clomiphene Citrate*:
- SERM
- A non steroidal agent
- Increases FSH/ LH release and induces ovulation.
- A weak estrogen receptor with striking antagonist effect selectively on the HPA axis estrogen receptors. BY binding tightly, it blocks estrogen induced inhibition of FSH/ LH release and induces ovulation.
*Used to treat secondary amenorrhea and anovulatory menstrual cycles.
Adverse Effects:
-Hot flushes, alopecia and headaches.
Toxicity: Multiple pregnancies, ovarian hyper stimulation syndrome (OHSS) and ovarian rupture (can lead to ovarian cancer)
(hMG- Human Menopausal Gonadotropin; hCG) and Bromocriptine:
- Ovulation Inducing Agents:
- ->(In case there is Hyperprolactemia- can cause secondary amenorrhoea)
Raloxifene*:
- A non steroidal SERM
- Mimics estrogen effect on the bone and decrease PTH induced bone resorption
- Helpful in the treatment of osteoporosis in post-menstrual women
- Likelihood of estrogens- induced breast/ endometrial carcinoma (when estrogen is used for the HRT) is avoided by using this agent.
–A good alternative to estrogens to protect against osteoporosis in post- menopausal women.
Drawback: Could cause deep vein thrombosis and pulmonary embolism.
