Hormonal contraceptives

What are the hormones controlling the menstrual cycle? GnRH FSH LH Estrogen Progesterone

GnRH release will cause FSH and LH release from the anterior pituitary FSH will stimulate follicles to grow, especially the Graafian follicle, which is the 'main' follicle. Normally 10 or so eggs are stimulated per cycle, but only one develops to maturity. The follicles will produce estrogen which is important for two processes Causes endometrial regeneration (gets endometrium ready for implantation) Causes the cells responsible for LH secretion to become more sensitive to GnRH, causing a massive spike in LH release The spike in LH and estrogen causes ovulation LH will stimulate the corpus luteum to develop, which then produces estrogens and progesterone Progesterone causes endometrial build-up to prepare for implantation It also triggers negative feedback to reduce the release of GnRH, FSH and LH. The cycle is split into two phases: Follicular phase (variable, days 1-14) Menstration (shedding of endometrium) Secretion of FSH and estrogen to develop endometrium and follicles Luteal phase (fixed, days 14-28) Growth of the endometrium Development of the corpus luteum

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How does the combination pill work? Contains an estrogen and a progesterone analogue Estrogen will: Inhibit FSH secretion due to feedback loop No FSH= no follicle production Stops the endometrium from breaking down as well, stops bleeding Progesterone will: Inhibit LH secretion due to feedback loop Prevents ovulation, as there is no LH spike Also thickens up the mucus in the cervix, which makes it hard for the sperm to get through Both will work together to make the endometrium unsuitable for implantation Remember: both progesterone and estrogen are released by the corpus luteum and placenta during pregnancy. Therefore, the body thinks it is pregnant How has the combination pill changed over the years? Initially used high doses of estrogen and estrane progestins Not suitable for use as the high doses of estrogen were linked to thrombosis formation The second generation used less estrogen and gonanes as the progestins One of the progestins is levonorgestrel, which is still used by itself in the emergency pill Problem is, the gonanes just have too much androgenic activity (women growing beards) The third generation used even less estrogen but still used gonanes Not available in NZ, had too much DVT risk But had a reduced androgenic effect due to other gonanes being used Fourth generation pills haven't dropped the estrogen levels, but have switched to non-testosterone derived progestins They have anti-mineralocorticoid and anti-androgenic effects, so they have a low side effect profile
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a low side effect profile Another change we saw was to do with the amounts of hormones in the pills: Monophasic pills had the same amount of hormones in each pill Biphasic pills has two types of pills in the pack with differing amounts of hormone Triphasic pills had three types of pills, each with a different amount of hormones, making them more complicated They thought having multiphasic pills would lead to better control But it's not true There are other routes of administration to consider: Patches Useful due to a continuous release of hormones (making hormone levels flat) while having a better adherence due to the long duration of action per patch. Otherwise same as the oral form Not available in NZ Vaginal rings Can also be used long term (3 weeks), which leads to good compliance Beware of rings being displaced Otherwise the same as the oral form Not available in NZ Side effects of contraceptives Generally mild symptoms are common Estrogen Breast tenerness Mood Weight gain Progestins Acne Etc Nausea Spotting/breakthrough periods Longer, heavier bleeds or more severe cramps But there are rarer (more severe) ones available MI (myocardial infarction) , DVT (Deep Vein Thrombosis) and stroke Estrogen causes hypercoaguability (makes the blood more prone to clotting) Therefore, it is contraindicated for women suffering from hypercoaguability; and treated as a caution for smokers Note: although it increases the chance of DVT, pregnancy has a greater chance for DVT Increased chance of breast cancer Remember: increased exposure to estrogen is a risk factor for breast cancer Endometrial cancer, colon cancer and ovarian cancer All reduced in chance Contraindications and cautions Undiagnosed endometrial bleeding Might make it worse Past or present circulatory disease Estrogen causes hypercoaguability Thrombophillia Estrogen causes hypercoaguability
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 Estrogen causes hypercoaguability Estrogen-induced hypertension Would increase hypertension Migrane with aura Migranes suggests reduced blood flow to the brain, estrogen increases the chance of stroke Liver disease Metabolised by the liver Lupus Pregnancy Daughters have an increased chance of cancer of the uterus Not contraindicated, but cautioned Smokers Hypertension Diabetes Interactions Metabolised by CYP3A4 Therefore, need to be very careful with CYP3A4 inducers, as they can cause failure (observe 7 day rule) Phenytoin Carbamazepines Rifampacin Anti-retrovirals 7 day rule is: Use barrier contraceptives during the unsafe period PLUS another 7 days after treatment is finished Broad-spectrum antibiotics? Normally, estrogen is conserved due to enterohepatic recycling If broad-spectrum antibiotics are used, the bacteria responsible for the recycling may be killed off, leading to therapeutic failure Only in combined oral contraceptives only, because estrogen is important Progesterone only pills have no estrogen, so they are not affected This has shown to be not true Then why do antibiotics cause therapeutic failure? Diarrhoea. It causes the loss of the pill, leading to treatment failure of both the combined oral contraceptive and progesterone only pill Observe 7 day rule Progesterone only Pill (POP) Also called the mini-pill Given continuously Compared to the COC which has 7 days of placebo pills Only contains progesterone analogues (progestins) Used for: Women with contraindications or cautions (see above) Breastfeeding females Estrogen causes negative feedback inhibition of prolactin, caused reduced milk production May also be given as a long acting implant in case of poor compliance Only has a 3 hour window, compared to 12 hours for the COCs Although it has a chance to prevent ovulation, its main mechanism of action
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 Although it has a chance to prevent ovulation, its main mechanism of action differs from COCs Instead, the progesterone will cause the mucus around the cervix to thicken, which prevents sperm from entering Theoretically, it's just as effective as COC But in reality, poor compliance leads to higher failure rates Male pills Not a popular idea Females just don't trust males Plus it's much easier to make a pill for females, as there are easy and safe methods to prevent pregnancy How would we pharmacologically use male contraception? Continuous treatment with testosterone Causes negative feedback inhibition as well Problem is we don't know its long term health effects, and it takes 3 months to work and a 3 month washout

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