Thirty Flashcards
(21 cards)
What do oral contraceptives do? What do they contain? What are monophasic pills like? Triphasic? Progestin only pills?
Oral contraceptives are pills that prevent pregnancy and are used for the treatment of
various menstrual disorders.
Combination Pills contain either estrogen (usually ethinyl estradiol) and one of a variety
of progestins.
Monophasic pills have a fixed dose of estrogen and a fixed dose of progestin.
They are generally in a 28-day pack with the last week consisting of placebos.
Triphasic pills have varying doses of the progestin in hopes of lowering the total
dose of hormones.
Progestin-only pills are taken daily without a placebo break.
NOTE..the placebos are not necessary. One can safely take oral contraceptive pills
continuously without having a break for menstruation.
What are 3 mechanisms of oral contraceptives?
Oral contraceptives work by:
- Suppression of ovulation by the suppression of gonadotropins (FSH LH)
- Cervical mucous thickening which may help prevent sperm passage
- Endometrial changes that lead to thinning of the uterine lining, and therefore decrease the ability for implantation.
What is the theoretical failure rate of OCPs? Actual failure rate? How effective are progestin-only pills? What is their mechanism?
OCPs theoretically have a failure rate of about 1%, however actual failure rate is closer to 3%.
Progestin-only pills are much less effective (3-7% failure). Their primary mechanism involves the cervical mucous and endometrial changes.
Describe some side effects of OCPs both individually and generally.
Side Effects
- Breakthrough bleeding which is very annoying for patients, appears to be related to the estrogen dose and may be seen in lower estrogen dose formulations.
- Nausea, breast tenderness headaches, amenorrhea
Most side effects resolve after 3 months of use, so better to wait than to switch formulations.
Describe various guidelines for OCPs related to CV disease.
- Cardiovascular disease
a. Estrogen (not progestins) increase clotting factors
b. Past users do not have an increase incidence of cardiovascular disease
c. All low-dose OC’s have an increased risk of thromboembolism
d. Smoking affects the risk of arterial thrombosis, not venous
e. Hypertension is an important additive risk factor for stroke
f. Low-dose OC’s (less than 50 micrograms) do not increase the risk of myocardial infarction or stroke in healthy, nonsmoking women, regardless of age
g. Almost all myocardial infarctions and strokes occur in high-dose products, or users with cardiovascular risk factors over the age of 35 (ie women who smoke)
h. Women with hypertension controlled by medication and less than 35 years old can take OC’S
What are 5 other complications of OCPs?
- OC’s can exacerbate systemic lupus erythematous and the vascular disease associated with lupus.
- High levels of triglycerides can be made worse by oral contraception.
- The overall risk of gallbladder disease is not increased, but in the first years of use, prior asymptomatic disease may be activated or accelerated.
- Weight gain on the pill is RARE.
- Hepatocellular adenomas have been reported.
Describe 5 ways in which OC affect cancer rates.
Oral contraception and Cancer
- OC’s PROTECT against endometrial cancer, and protection may last 15 years after discontinuing the pill
- OC’s PROTECT against ovarian cancer
- Studies have suggested that OC’s may cause cervical cancer, but this may be due to enhanced detection.
- Hepatocelluar adenomas
- OC’s decrease the incidence of benign breast disease. Data indicate that young women who begin use before age 20 have higher relative risks of breast cancer during current use and in the 5 years after stopping, this is a time period when breast cancer is very rare; and, thus there would be little impact on the actual number of breast
cancers.
What are some drug interactions with OCs? What is the interaction like?
Drug Interactions
Rifampin, Phenobarbital, Phenytoin, Primidone, Carbamazepin (P450 Induction)
What are some benefits of OCPs?
Benefits of oral contraceptives
- effective contraception
a. Less need for induced abortions and surgical strerlization. - Less endometrial cancer
- Less ovarian cancer
- Fewer ectopic pregnancies
- More regular menses (less flow, less dysmenorrhea, less anemia)
- Less salpingitis
- Probably less endometriosis
- Possibly less benign breast disease, rheumatoid arthritis, protection against atherosclerosis, increased bone density, fewer fibroids, fewer ovarian cysts
premenstrual syndrome.
Definitely Beneficial
- dysfunctional uterine bleeding
- dysmenorrhea
- mittleschmerz
- acne and hirsutism
- hormone therapy for hypothalamic amenorrhea
- prevention of menstrual anemia
What is the pathophys of menopause? Symptoms?
With the onset of menopause (loss of
oocytes/follicles), ovarian production of estrogen is significantly reduced, leading to
dramatic physiologic changes including:
- hot flushes
- mood disturbances
- thinning of genitourinary tissues
- loss of calcium from the skeleton
- metabolic shift to a more atherogenic lipoprotein profile
How does HRT help with CNS symptoms?
Central Nervous System Symptoms
- estrogen is helpful in relieving the symptoms of hot flushes, insomnia, irritability, poor memory, anxiety and headache
- studies suggest that Alzheimer’s disease may be retarded with estrogen use (but not eliminated)
- progestins may be effective in reducing vasomotor symptoms in women who are unable to take estrogens, but are not as effective
Describe post menopausal bone loss. How does HRT help?
-loss of bone density is associated in aging in both men and women. In contrast to bone
loss in men, bone loss in women accelerates at the onset of menopause on average at a
rate of 3% per year for the first 5 years and 1% per year thereafter. However, in some
women bone loss at this time may exceed 5% per year. Hip fractures frequently occur
15-25 years after menopause with an overall mortality rate of 30% within 1 year of hip
fracture. Other fractures associated with osteoporosis include fractures of the vertebrae,
distal forearm, and proximal humerus.
-bone loss is due to loss of mineral density resulting from bone resorption exceeding the
rate of bone formation. Osteoporosis is diagnosed when bone mineral density decreases
to less than 2.5 standard deviations below the young adult peak mean..
-0.03 mg of conjugated estrogens has been shown to be effective in preventing further
bone loss by inhibiting osteoclastic activity when compared with a placebo
Describe the genitourinary changes that occur post-menopause. How does HRT help with these?
-since the urethra and vagina are estrogen responsive tissues, withdrawal of estrogen
during the menopause results in a reduction in the overall mitotic activity in these tissues,
with a decrese in vascularity and thinning of the mucosal layer. The vaginal and urethral
mucosa appear pale, dry and flattened. These hypoestrogenic changes in the vaginal
mucosa are associated withvaginal dryness, dyspareunia, and atrophic vaginitis. Atrophy
of the urethral mucosa is associated with a greater incidence of urethritis, decreased
urethral pressure, and a possible increased incidence of urinary incontinence.
- systemic estrogen and local estrogen creams and rings can reverse most of these
changes. Hormone replacement therapy can decrease the risk of urinary tract infection
and microscopic hematuria.
How can HRT help in hypogonadal conditions?
Individuals who fail to undergo pubertal maturation due to causes such as ovarian failure,
gonadal dysgenesis, isolated gonadotropin deficiency, require estrogen replacement
therapy to induce the normal adult female phenotype.
Summarize the relation between CV disease and HRT.
See slides, but bottom line is that the WHI (Women’s Health Initiative) and HERS
showed that women with an average age of 63 and 68, respectively, should not be given
Hormone Therapy for the prevention of coronary heart disease. The controversy is that
the study did not address women who were perimenopausal (just starting menopause)
who are women more likely to be starting HRT. Several observational and animal
studies show a cardioprotective effect of estrogen in these women. Stay tuned for this
one.
How is HRT used in endometrial hyperplasia or cancer.
-unopposed estrogen (estrogen without progesterone) is associated with endometrial
cancer, therefore, in a woman with a uterus, cyclic or continuous progestin therapy is
required to protect the endometrium from hyperplastic transformation during estrogen
replacement therapy.
What are some guidelines for the estrogen component of HRT? Progestin component?
-the lowest effect dose of estrogen that will relieve the patient’s symptoms and provide
cardiovascular and bone protection should be used. Oral therapy, due to its first past
effect though the liver results in higher increases in HDL cholesterol, decreases in LDL
and increases in triglycerides. This is not seen with the patch.
Progestin component
There are several types of progestin components. The most commonly used is
medroxyprogesterone acetate, given 5-10 mg during the last 12-14 days of estrogen
administration, or 2.5 mg when given daily.
Oral micronized progesterone is now available in doses of 200-300 mg per day is
sufficient to protect against endometrial hyperplasia. This formulation had better lipid
changes than with medroxyprogesterone acetate, but whether or not that translates into a
healthier heart is unknown.
Norethindrone is the most potent oral progestin compound available for hormone
replacement therapy at a dose of 1mg.
What are some estrogen-progestin combination regimens?
Estrogens and progestins can be given in a variety of combinations. Two common
sequential methods that were commonly used were using estrogen continuously, and
giving progesterone for the first 15 days of the month. This will often result in menses
END 30-7
and is not a real hit with post menopausal patients who want their bleeding to be over
with and done. The second sequential method involves estrogen for the first 25 days of
each month, with progestin added the last ten days, also with a resultant menses.
Continuous therapy uses estrogen and progestins continuously, with resultant
amenorrhea. Now, there are pills and patches with the estrogen and the progestin
combined together. PREMPRO was the combination pill that was used in the WHI trial,
but the FDA warns against all hormone formulations for reasons stated elsewhere.
How effective are progestin only regimens? When are estrogen only regimens used? What are the results of estrogen-androgen regimens?
Progestin-Only
For women who can not take estrogen, progestins alone may be helpful in the treatment
of vasomotor flushes and are used for contraception in breastfeeding mothers.
Estrogen-Only
For women who do not have a uterus or women who agree to have their endometrium
monitored closely.
Estrogen-Androgen Regimens
- the use of androgens may increase total cholesterol (increase LDL and decrease HDL
cholesterol) , and may cause hirsutism, acne and weith gain.
What is raloxifene? What does it do? What doesn’t it do?
Selective Estrogen Modulators (SERMS)
-Raloxifene is currently recommended for osteoporosis at 60mg per day. In contrast to
oral estrogen, HDL and triglycerides were unchanged during the treatment. The risk of
venous thrombolic phenomena is similar to estrogen. Raloxifene does not help in the
treatment of hot flashes. Reloxifene may be protective for breast cancer. This is
currently being investigated.
What are some absolute contraindications to HRT? What are some relative contraindications?
ABSOLUTE CONTRAINDICATIONS
Medical conditions related to estrogen exposure
- Recent vascular thrombosis
- Neuroophthalmologic vascular disease
- Recent history of endometrial carcinoma
- History of breast cancer (?)
- Undiagnosed vaginal bleeding
Medical conditions related to estrogen metabolism
- Acute hepatic disease
- Chronically impaired liver function
RELATIVE CONTRAINDICATIONS
- Seizure disorders
- High serum triglycerides
- Current gallbladder disease
- Migraine headaches
