39-Hormonal contraception Flashcards
Contraception continued
-Blockage of implantation \+IUD (can also contain hormones) -Emergency contraception \+Morning after pill \+Prevents implantation \+Not effective after implantation- not an abortifacient)
Development of oral contraceptive
-1920s: observation that ovarian extracts could be used in the control fertility
+Physiological mechanism known: Pregnant women don’t ovulate; persistence of corpus luteum cause infertility
+Progesterone interferes with ovulation (animal studies)
-1930s: potent oral oestrogen synthesised ethinyloestradiol. Progesterone synthesised from steroid found in Mexican yams
-1951: Synthesis of norethisterone, an orally active progesterone analogue
Trials of progesterone
-Stopping progesterone treatment causes a withdrawal bleed
+Not a real period
-21 days with 7 day break: good response and regular bleeding
+BUT when a purified progesterone used: Increased pregnancy rate and menstrual disturbance
-Impurity identified as an oestrogen
+Combined oral contraceptives
Causes of side effects
-First COC in USA late 1950s in UK in 1961. Efficacy quickly established
-Association with cardiovascular disease quickly became apparent (venous thrombosis-embolism
-Oestrogen component of COC responsible
+Original EE dose: 150mcg
+Since 1960s: 50 mcg
+Now commonly: 25-30mcg used
Other problems
-Problems with progesterone component
+Reduction in HDL ChE
-Second and third generation progestogens developed to overcome this risk
+BUT increased risk of DVT with 3rd generation caused dramatic reduction in prescribing
Mechanism of contraceptive effects
-COC inhibit ovulation by suppressing release of gonadotrophins (Suppression of the HPG)
-Feedback inhibition at level of pituitary and or hypothalamus
-FSH secretion suppressed
+No maturation of follicles
-No mild cycle LH surge
+No ovulation
-No development of corpus luteum
Additional effect of progesterone component
-Progestogens
-Increase viscosity and decrease volume of cervical mucus: barrier to sperm
-Modify tubal motility: affect transport of ova from ovary to uterus. May interfere with sperm penetration
-Progestogens provide unreceptive and thin endometrium for implantation
+Disruption of normal cyclical changes in endometrium
+Suppressed endometrial thickening
Indications for COC use
1) contraception
2) Menstrual disorders (NB exclude underlying pathology first)
-Efficacy COCs
-Failure rate low: 0.1-7.0/100 women years
+Caused by missed pills, drug interactions, temporary illness (D&V)
+Enzymes including drugs enhance metabolism of oestrogen and progesterone e.g. rifampicin
+Altered colonic flora interfere with enterohepatic recirculation of oestrogen (antibiotics)
Oestrogens
-Natural hormone is estradiol
-Synthetic hormones ethinylostradiol (EE), mestranol
+Mestranol is a pro-drug of EE
+Not bioequivalent 50 mcg= 35 mcg EE
-Dose oestrogen reduced from original 50 mcg + to combat side effects
+See BNF for preparations
+20-35 mcg EE daily. Mestranol
Progestogens
-Natural hormone progesterone
-2nd generation drugs are derivatives of testosterone
+Noresthisterone, levonorgestrel
+Ethyndiol, norethyndiol, lynoestrenol
-3rd generation drugs are 19-nor or 13-ethyl steroids
+Desogestrol, gestodene, norgestimate
-Relative potency 3rd generation > older
+Developed to try and reduce progestogen linked side effects
Health risks COCs
-Major risks
+CV disease (MI, stroke, VTE)
+Cancer (particularly breast cancer oestrogen can stimulate cancer cells to divide)
-Minor risks
+Oestrogenic: nausea, weight gain, breakthrough bleeding
+Progestogenic: breast fullness; depression
-Health benefits
+Ovarian cancer, endometrial cancer decrease
+PID, ovarian cysts, bengin brett disease decrease
-Protection from maternal mortality
How do progesterone only contraceptives work
-Mini Pill- Sometimes effects HPA and ovulation but not all the time relies on other progesterone effect (increase mucus thickness, thin endometrium, reduced motility)
+Low dose progesterone
+Administered daily
-Injection
+Higher dose; administered as oily injection
+Also available in IUDs, implants
Progesterone oral contraceptives
-Synthetic progestogens suppress FSH and LH at level of pituitary/hypothalamus
+BUT pituitary can still respond to GnRH
+Leads to cycles that are anovulatory OR ovulatory depending on degree of HPG suppression
-Ovum transport decrease and development of endometrium decrease: Fertilisation or implantation decreased
+thin, unreceptive endometrium, thick viscous mucus
Progesterone depot injections
-Medroxyprogesterone acetate (MPA) \+Synthesised in 1950s used for endometriosis and threatened miscarriage (progesterone hormone of pregnancy) -Long term contraceptive \+Social implications -Products available now \+Depot MPA (DMPA) \+Noresthisterone enanthate (NETEN)
Mode of action MPA
-Ovulation inhibited through inhibition of hypothalamus and pituitary
+Release of GnRH inhibited
+Secretion of FSH and LH reduced, mainly anovulatory cycles
+Ovarian secretion of oestrogen and progesterone inhibited
-Endometrial development suppressed and thickening
