M4s2 Regulation Of Fertiliy Flashcards
Introduction to regulation of fertility and contraception
-medical science has contributed to allowing individuals to have more precise control of their reproduction by the development of various forms of contraception
-while hormonal and non-hormonal types of contraception exist only know hormonal including oral contraceptives, injectable contraceptives (I.e., Depo-Provera), intrauterine devices (IUDS) and the transdermal patch
Contraception
The prevention of conception
The monthly ovarian cycle
-involves the intricate and coordinated interaction of number of hormones and factors
-mechanism of action of hormonal contraceptives is associated with changes to the hormones in the ovarian
Mechanism of action of hormonal contraceptives
-mechanism of action of all hormonal contraceptives is essentially the same
Inhibit hormone release
-hormonal contraceptives inhibit the release of gonadotropin-release hormone (GnRH) from the hypothalamus
-as a result, pituitary not stimulated to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in no follicular maturation and the inhibition of ovulation
Inhibit sperm migration
-hormonal contraceptives commonly include progestins, which alter the secretions of the endometrial gland to a scant, think fluid not optimal for sperm migration
Infinity ovum implantation
Finally, hormonal contraceptives cause the endometrium to not fully develop making it unsuitable for implantation of fertilized ovum
*refer to goodnotes for image
Homornal contraceptives that modify ovarian cycle: oral contraceptives
Oral contraceptives
-refers to product containing both estrogen and a progestin
-preparations which contain both estrogen and progestin are the most effective oral contraceptives developed to date, and are widely used
Types of oral contraceptives
-vary in amping and type of hormones present in pill, as well as how often pill taken
Fixed combination:
-pill have fixed combination of estrogen and progestin
- one preparation is intended to be taken for 21 dats out of a 28 day cycle with menses occurring during the 7 day pill-free/placebo period
-first product Enovid-E became available in Canada in 1961
-some foxed combination pill regimens taken for 28 dats each cycle with no or very infrequent drug free periods
-advantage of this preparation is that menstruation eliminated for duration of therapy, which particularly useful for women who have difficult or problematic menstruations
Multiphasic
-contain fixed amount of estrogen and variable amounts of progestin: progestin increases week to week
-these “phasic” preparations are currently the oral contraceptives of choice
-within oral contraceptives, hormone dose kept to minimum and adverse events believed to be reduced as compared to fixed-dose combination
-advantage: hormonal sequence more closely mimics pattern of hormones released in normal ovarian cycle
Progestin only pill
-aka mini-pill
-contains a daily low dose of progestin
-taken as long as the drug is needed
-patient acceptability less than with the estrogen-progestin combinations, since breakthrough bleeding (bleeding between periods) is often problem
-efficacy in preventing pregnancy is slightly less than with combination products
Adverse effects of combination oral contraceptives
-approximately 20 million women in North America taking these preparations daily
-as such, oral contraceptives are probably one of the most studied drug class in terms of toxicities
-large number of toxicities been reported and range from mild to severe
Mild:
-nausea which caused by estrogen component and usually abates 1 or 2 cycles
-edema as estrogen and progestin cause water retention
- headache (if severe drug must be stopped)
Moderate:
Breakthrough bleeding, weight gain, increased skin pigmentation (due to estrogen), acne and hirsutism (abnormal growth of hair on a person’s face and body, especially female) (progestin is believed to cause these two responses, as some of them have androgenic properties) and increases vaginal and uterine infections
-post drug amenorrhea (absence of menstruation) occurs in a few patients and may persist for months
Serous adverse effects of combination oral contraceptives
Blood clots - estrogen induce production of some factors that required for blood coauglation, increasing the death rate from blood clots from 1 per 100,000 women per year for non-users of pill to 3 per 100,000 women per year for users. It can be argued that this is very low incidence, but it is nonetheless increased
Heart attack - estrogen-progestin oral contraceptives are associated with a small increased risk of heart attack. Risk greater if patient obese, or if patient smokes. Believed to be associated with progestin component. Some newer progestins may be free of this effect
Stroke - women taking oral contraceptives have increased risk for cerebrovascular disease (stroke). Risk is greater if patient over age 35 but all ages affected
Hypertension - cardiovascular disease more prevalent in women over 35 years of age
Cancer - endometrial and ovarian cancer risks reduced and no apparent increased risk of developing breast cancer. No clear decision made with respect to cervical cancer, as complicated by human papilloma virus (HPV) infection
Due to adverse effects, women should not be taking a combined estrogen-progestin oral contraceptive if they have
-thromboembolic disease (blood clotting disease)
-cerebrovascular disease
-impaired liver function or overt liver disease
-carcinoma of the breast or estrogen-dependent neoplasia
-undiagnosed bleeding
-migraines with auras
-pregnancy or suspected pregnancy
-oral contraceptives during pregnancy may be associated with congenital limb deformities, masculinization and cryptorchildism (undescended testes)
Non-contraceptive benefits of oral contraceptives
-reduced risk of ovarian cysts
-reduced risk of ovarian and endometrial cancer
-reduced in incidence of ectopic pregnancy ( a fertilized egg implants itself outside of the uterus, typically in the fallopian tubes
-less iron deficiency anemia, as menstrual flow is reduced
-less acne and hirsutism (for those containing newer progestins with less androgenic effects
Homornal contraceptives that modify ovarian cycle: Depo-Provera
-also known as “the shot”
-type of contraceptive injection
-progestin dose is injected intramuscularly every 3 months and provides contraception for roughly the same timeframe
Adverse effects
-both depo-provera and the mini-pill are progestin-only hormonal contraceptives, resulting in similar adverse effects
-breakthrough bleeding
-alter the profile of plasma lipids, increasing low density lipoproteins and decreasing high density lipoproteins, which causes a small increase in risk of coronary vascular disease *effect does not occur with some newer agents
Homornal contraceptives that modify ovarian cycle: (INTRAUTERIN DEVICES) IUD
-implanted into uterus by medical professional
-most common type releases levonorgestrel (a progestin) and effective for 5 years
-good choice for women who wish to have long term reversible contraception and where estrogen is contraindicated
Adverse effects:
Heavy menstrual flow
Pelvic discomfort
Increased uterine infections
Homornal contraceptives that modify ovarian cycle: transdermal contraceptive patch
-contains estrogen and progestin in a attach that applied to skin
-drug deleivered at constant rate for 7 days, requiring three patches per cycle
-mechanism, of action is same for combined estrogen-progestin oral contraceptives
Pros and cons of hormonal contraceptives
-best method vary per patient
‘*refer to goodnotes chart
Efficacy of hormonal contraceptives
- refer to goodnotes chart
*refer to table in goodnotes
Spermatogenesis
Sperm development
Male contraceptives
-historically contraceptives have been targeted to females
-now researchers do men too
-can be taken orally or injected
-not yet reached Canadian market
-attempts to inhibit spermatogensis have been largely unsuccessful, with most drugs and processes studied resulting in unacceptable rates of fertility
Process of spermatogenesis
*refer to goodnotes for flow chart and info
Potential male contraceptives
-4 main compounds (or combinations of compounds) have been tested for use as male contraceptives
-primary administered orally or via injection
Androgen-based
-inhibit release of GnRH and thus spermatogenesis
-studies conducted to date, typically an injectable form of androgen was administered intramuscularly and two major problems were encountered
-only 80% of subjects responded with a lowering of sperm count to less than 4 million/mL
-the excess androgen enhanced the secondary sex characteristics, including aggression
Estrogens
-when administered to men (did they mean to say women?) suppress GnRH release and in turn spermatogenesis
-when estrogens are given to men however, testosterone production decreases, as dose sex drive, and men develop feminine characteristics
-thus, subject infertile but also lost interest in sex
-to overcome deleterious effects of estrogen on secondary sex characteristics, small amounts of androgens were added to regimen. With this combined estrogen-androgen regimen, only 60% of subjects became infertile, and adverse effects from estrogen were too numerous
Progestin and androgen
- a synthetic progestin used to inhibit the release of GnRH
- results in loss of spermatogenesis as well as testosterone production, decreasing male secondary sex characteristics
-androgen is added to regimen to replace the lost testosterone and hence maintain the secondary sex characteristics
-method has shown more promise than other methods, but finding the appropriate dose of exogenous androgen major challenge
Gossypol
-compound obtain from cottonseed
-destroys elements of seminiferous tubules, decreasing sperm production, but does not alter sex drive or function of testosterone
-drug has undergone extensive clinical trials in china; appropriate use led to infertile sperm counts in 99% of subjects. Recovery of sperm count after discontinuing use of gossypol not always guaranteed, but more apt to occur if sperm count does not fall too low and duration of treatment does not exceed two years
-hypokalemia (low potassium) has been major problem reported, resulting in transient paralysis. Drug was undergoing clinical trials in North America but how abandoned
