Womens Health: Combined Oral Contraceptives (Case 2)

menstrual suppression risks

-unschedualed bleeding and spotting -although most say safe to use; there is limited evidence regarding long term safety -increased cost of the medication -unknown effect on fertility

Vaginal Contraceptive Ring NUVARING (Ethinyl Estradiol and Etonogestrel)

ESTOGEN AND PROGESTIN COMBINATION MOA: similar to COC Combination hormonal contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility associated with less unscheduled bleeding than the COC and the duration of menstrual bleeding is significantly shorter than that seen with the contraceptive patch PK -release rate is constant or not time dependent (zero order) - F= 100% for etonorgestrel and 55% for ethinylestradiol BIOPHARM -nuvaring is a flexible soft transparent ring made of ethylene vinyl acetate copolymer with an outer diameter of 54mm and a cross sectional diamter of 4 mm DOSING The ring releases 15 mg of EE and 120 mg of the progestin ENG (the active metabolite of desogestrel) per day, which is absorbed through the vaginal epithelium. sustainable plasma concentrations for 3 weeks (should be removed at the end of the 3rd week) non contraceptive benefits: -reduction in menstrual blood loss and an improvement in duration of menses and in hemoglobin and ferritin levels after 3 cycles of treatment. -a reduction in dysmenorrhea, premenstrual syndrome, menstrual headaches and migraines, hirsutism and hyperandrogenemia, and endometriotic nodule volume patient education: During intercourse the ring could be felt.... The ring does not need to be removed during intercourse, although some women may choose to do so. If it is removed, it should be reinserted within 3 hours.

GQ 14)

GQ14 Tricyclen: contains 35 micrograms EE With carbamazepine, increase Cl by 2.5 x and decrease F by 50%. Calculate dosage adjustment necessary to maintain same Css of EE. Css= F x D/Cl Css1=Css2 aka F1 x D1/Cl1 = F2 x D2/Cl2 => 35 x 1/1 = D2 x 0.5/2.5 => D= 35 x 2.5/0.5 => D=175 micrograms EE which is 5x the normal amount.

combined hormonal contraceptives (CHC)

contraceptive methods that contain both an estrogen and a progestin

Generic products

generic formulation manufacturing processes and facilities must meet Health Canada standards for Good Manufacturing Practices. Generic products are not required to, and have not had, the safety, side effect, and efficacy trials that have been done for the original branded products. There is no evidence that generic oral contra- ceptive pills are either equally or less effective or safe compared with their brand name equivalents.

vaginal drug delivery

vaginal canal is on average 4-6 inches -vaginal tissues are highly perfused and drained directly into vena cava by passing first pass metabolism by the liver. -vaginal lumen has a normal pH 4-5 due to continuous secretion of ovarian hormones and high concentrations of lactic acid

Risks of using Diane 35 long term after acne is cleared GQ 9 e

- Discontinue 3-4 cycles after acne resolved ADVERSE EFFCECTS of DIANE 35: Major: thromboembolism (rare), stroke, retinal artery thrombosis, MI, benign liver tumor, cholelithiasis, hypertension, liver carcinoma!!! 4X more risk of VTE comapred to other COCs using it for long term is an off label use.

3 types of estrogen used in COCs

-Ethynyl Estradiol (EE) -Estradiol Valerate (E2V) -7 beta-estradiol (E2)

menstrual suppression: potential indications

-PMS -Endometriosis -abnormal uterine bleeding -women experiencing estrogen withdrawal Sxs on HFI (headaches) -perimenopause -women undergoing cancer tehrapy which may experience severe uterine bleeding

Transdermal delivery of estrogen disadvantages

-contact dermatitis -topical side effect (increase in skin thickness) -absoprtion is affected by skin condition (skin thickness, degree of hydration etc) >>>> INCREASED AUC of EE is observed when the patch is applied in condition like exercise, heat, humid conditions. this increase was not observed with norelgestromin

menstrual suppression benefits

-fewer menses may lead to: less dysmenorrhea, less premenstrual syndrome and less bleeding. -fewer symptoms related to the hormone free interval (headaches) -convenience -cost savings (pads) -enhanced compliance -maintains and may even increase contraceptive efficacy

COC Disadvantages

-increased risk of venous thromboembolism COC and Breast Cancer: no increase in the risk of breast cancer or breast cancer mortality in women who have used combined oral contraceptive pills (COCs) compared with non-users (II-2). There may be a slight increase in breast cancer in current and/or recent COC users (II-2). The use of COCs in BRCA1/2 carriers is controversial but appears to be associated with a decreased risk of ovarian cancer and no increase in the risk of breast cancer

Transdermal delivery of estrogen advantages

-minimize GI AE (HOWEVER: higher rate of nausea has been reported with Evra patch comapred to the ring and COC) -avoid first pass effect in liver (HOWEVER... watch out for risk of CV events in heavy smokers and elderly) -minimize indiction effect on liver protein synthesis -more balanced therapeutic effects -enhanced complicance

factors affecting percutaneous drug absorption

-surface are of drug application -particion ccoefficient and state of ionization of the drug -molecualr size -skin condition (hydration will elad to inc absorption) -skin texture (inc abs from thin and horny skin comapred to thick skin) -contact duration

PMS and Drospirenone

Drospirenone is related to the aldosterone antagonist spironolactone and has both progestational and antiandrogenic activity.[20] A Cochrane review of 5 trials shows drospirenone-containing COCs may benefit women with premenstrual dysphoric disorder (PMDD), but there is limited evidence of benefit for milder disease or for greater than 3 cycles of use. (for yaz PMS was a side effect....)

GQ 12 c - is there anyway to tell if a COC is not working (aside from pregnancy)

Drug interactions may diminish the efficacy of birth control meds. -side effect of an antibiotic would be diarrhea and nausea.. which means backup contraception should be used aside from the COC as some of the COC may not be absorbed. diarrhea would eliminate enterohepatic circulation thus decreased absorption of the COC >>>>>>check thiiiisssss Due to other medications, the effect of Estrogen or Progestin may be diminished What to look out for when concerned about Estrogen deficiency - early bleeding and spotting on days 1-9 - pelvic relaxation SX -atrophic vaginitis - Vasomotor SX - continuous bleeding or spotting - decerase in flow -absence of withdrawal bleeding -nervousness What to look out for when concerned about Progestin deficiency: - late bleeding and spotting days 10-21 - delayed withdrawal bleeding What to look out for when concerned about Estrogen Excess: - hypermenorrhea, clotting, menorrhagia -inc breast size -inc uterine fibroid growth -dysmenorrhea -hypertension -UTI What to look out for when concerned about progestin excess: -depression -breast tenderness -libido decrease -weight gain -inc appetite -fatigue -hypertension

Difference between Yasmin, Yaz and YazPlus

YAZ (EE 20 mcg, Drosperinone 3 mg) YAZ PLUS ( EE20 mcg, Drospirenone 3 mg, levomefolate calcium 0.45 mg) YASMIN (EE 30 mcg, Drospirenone 3 mg) YAZ PLUS>>>> Levomefolate is the active form of folic acid. Folic acid is needed for the body to produce blood cells. For women who take birth control pills, the body is not able to turn folic acid into levomefolate as easily as it could when she was not taking birth control. The levomefolate replaces the folic acid the body is not creating. (28 day regimens: ALL contain more than 21 days of active medication)

what is meant by LOW dose and how do these differ from current higher dose COCs on the market

the dose is referring to the estrogen component of the COC. LOW dose: 20-25 mcg ethinyl estradiol ULTRA LOW dose: 10 mcg ethinyl estradiol High dose: 30-40 mcg ethinyl estradiol

MRI and CT scan concerns with the Evra Patch GQ 3

the evra patch does not contain any metals components, thus it would be ok to stay applied on the skin while the patient gets an MRI or CT scan

Weight gain and COC?

weight gain could be an observed ADR with COC use. this may be due to increased appetite in the first month >>>may be cyclical due to Na+ and H2O retention... - studies have failed to show any association between COCs and weight gain - overall little or no weight gain is observed with low dose OCs or POP. >>> YASMIN, YAZ have possibly less weight gain associated with them due to their diuretic effect?

CONTRAINDICATIO NS for COC , ring, patch check thisssssssssss

- medical conditions are categorized into 4 categories. (MEC: Medical Eligibility Criteria) category 4> represents unacceptable health risk if contraception method is used. category 3> risks > advatanges if contraception method is sued category 2> advatanges> risks for using contraception method category 1> no restriction for use of contraceptive method category 4: <4 weeks postpartum (breastfeeding) <21 days postpartum (not breast feeding) smoker > 35 years (>15 cigs/day) vascular disease Hypertension (systolic > or eq to 160 or diastolic > or eq to 100) Acute DVT/PE orrrr history of DVT/PE, not receiving anticoagulant therapy Current breast cancer category 3: 4-6 weeks postpartum (breast feeding) 3-6 weeks postpartum (not breast feeding) history of DVT history of breats cancer certain anticonvulsant use ABSOLUTE CI to COCs: - breast cancer -cerebrovascular disease/ complicated valvular heart disease -curent or past history of thromboembolism -diabetes with microvascular complications -history or current MI or heart disease -<6 weeks postpartum if BF -migraines with aura at any age -hypertension -severe cirrhosis or liver tumor -smoker >35 years of age (> or equal to 15 cigs/day) category 4.... if less than 15 cigs per day category 3 TRANSDERMAL PATCH: For women weighing 90 kg or more, this method may not be effective. Obesity may also affect follicular development through various mechanisms in patients taking oral contraceptives VAGINAL RINGL: CONTRAINDICATIONS: Although not contraindications to use of the ring, women with significant pelvic relaxation, vaginal stenosis, or obstruction (if they prevent retention of the ring); condi- tions that make the vagina more susceptible to irritation or ulceration; or an inability or unwillingness to touch their genitals may not be good candidates for the ring.1

Eligibility for COC

-A blood pressure measurement is the only examination and/or investigation that is required prior to initiating COC in healthy women. -baseline BMI may be important to measure for future monitoring -the CHC can be started at anytime duirng the menstrual cycle provided that the patient is not pregannat. (pill exposure just prior to or during preganancy is not associated with an increased risk of major birth defects) - Health care providers should consider advising women who are initi- ating contraception to start their combined hormonal contraception (CHC) immediately (Quick Start) provided that they are reasonably certain that the woman is not pregnant. Back-up contraception (barrier method) or abstinence should be used for the first 7 consecutive days of CHC use unless CHC was initiated on the first day of menses

Effectiveness of COCs

-Although highly effective with perfect use, typical use failure rates for combined hormonal contraceptives, including the combined oral contraceptive pill, are as high as 9%

COC Benefits

-Decreased menstrual bleeding - incerassed BMD -Decreased acne -fewer endometriosis related symptoms -decreased risk of ovarian and endometrial cancers

GQ 13) Clinically significant drug interactions with COCs

Anticonvulsants Phenytoin, carbamazepine, barbiturates, topiramate, oxcarbazepine, primidone) decrease serum concentration and efficacy of COC's due to induction of CYP3A4 - category 3 (((((((((MANAGEMENT: Ensure an ethinyl estradiol dose of at least 30mcg while on concurrent anticonvulsant therapy Alternatively, if a women is taking an enzyme-inducing medication short term (≤2 months), an option is to take one COC pill daily (at least 30 mcg EE) for 3 or 4 cycles without a break (extended regimen or "tricycling") followed by a hormone-free interval of 4 days. For patients on enzyme-inducing medications long term, the use of 2 monophasic COC pills containing at least 50 mcg EE (e.g., 20 mcg and 30 mcg COCs) with a pill-free interval of 4 days can be used))))) check thissssssssssssssss " Several antiepileptic drugs induce SHBG, resulting in lower levels of free serum progestins, which may contribute to COC failure " (progestins are primarily bound to SHBG and estrogens are primarily bound to albumin) Anticonvulsants Lamotrigine : decreased lamotrigine effect is observed MANAGEMENT: may need to increase the dose of lamotrigine. Increases in lamotrigine clearance and evidence of increased formation of the lamotrigine N-2-glucuronide suggest that the most likely mechanism for this interaction is enhanced lamotrigine glucuronidation Anticoagulants COC may decrease effect of these. use with caution and monitor INR Rifampin/ rifabutin/griseofulvin Decreases efficacy of COC's due to induction of CYP3A4 - category 3 MANAGEMENT: Ensure an ethinyl estradiol dose of at least 30mcg while on concurrent rifampin/rifabutin therapy. use backup contraception Antiretroviral therapy may lead to increased or decreased contraceptive effect. St.John's Wort May decrease efficacy of COC's and increase incidence of BTB and ovulation due to induction of CYP3A4 - category 2 MANAGEMENT: Interaction dependent on dose and concentration of active ingredients in selected St. John's Wort preparation, just avoid St. John's Wort altogether >>> Reduced effectiveness of the oral contraceptive, should it occur, is more likely with the low-dose formulations. (Especially with ultralow dose like LOLO) some drugs may increase COC concentrations: acetaminophen and ascorbic acid (competing for sulfate and glucuronide conjugation)

Using hormonal contraceptives for ACNE GQ 7

COCs also lower the amount of androgens in the body, which results in decreased sebum. - However, certain birth control causes acne. Those that contain progestin can promote acne and worsen breakouts. This is oftentimes why some people say that they experience increased acne on birth control. this is because progestin binds to SHBG and displaces testosterone, thus leading to more free testosterone which then bind to testosterone receptors more readily leading to androgenic effects (testosterone increases sebum production as it enhances sebaceous gland activity) - Skin clears up faster with a birth control pill that contains a moderate to high level of estrogen.(All CHCs can be beneficial in acne due to estrogen binding to SHBG). Products containing third-generation progestins (e.g., desogestrel, norgestimate) are less androgenic and may be useful in acne > official acne indication: ALESSE,Tri-Cyclen, YASMIN, YAZ and Diane35/ CYESTRA-35 DIane 35 is not indicated for contraception in Canada. - it contains (2 mg cyproterone acetate and 0.035 mg ethinyl estradiol) While not approved by Health Canada for contraception, cyproterone acetate is a progestin with antiandrogenic activity that is used in combination with EE for the treatment of moderate to severe acne. 1.decrease androgen production at the level of the ovary 2. through the metabolization of estrogen in the liver, estrogen increases sex hormone binding globulin (SHBG), binding free circulating testosterone and rendering it unavailable to bind and activate the androgen receptor. 3. COCs reduce 5-alfa-reductase activity (converts testosterone to dehydrotestosterone which is the active form of testosterone) and block the androgen receptor

COC regimens: Monophasic vs multiphasic COCS

CYCLIC : traditional with 21 days of the active pill and 7 day HFI SHORTENED HFI : 24 days of active pills with 4 day PFI (YAZ) or 26 days of the active pills with 2 days PFI (LOLO) EXTENDED CYCLE: 84 days of the active pills, 7 day PFI (Seasonale) or 84 day E and P, 7 day E only. (Seasonique) multiphasic formulations were intially developed with the intent of loweing the total steroid content of COC and improving cycle control significnat diferences have not been shown between monophasic and triphasic COCs in regards to bleeding pattern or efficacy. MONOPHASIC: each tablet contains a fixed amount of estrogen and progestin (ACTIVE PILLS AND PLACEBO PILLS) >>>> 2 colors MULTIPHASIC: different days contain diffrent amounts of estrogen and progestin (HENCE BIPHASIC AND TRIPHASIC) BIPHASIC PILLS: deliver the same amount of estrogen every day for the first 21 days of the cycle. During the first half of the cycle, the progestin/estrogen ratio is lower to allow the lining of the uterus (endometrium) to thicken as it normally does during the menstrual cycle. During the second half of the cycle, the progestin/estrogen ratio is higher to allow the normal shedding of the lining of the uterus to occur. >>>> 3 colors TRIPHASIC PILLS: have constant or changing estrogen concentrations and varying progestin concentrations throughout the cycle >>>> 4 colors

Transdermal Contraceptive patch EVRA (Ethinyl Estradiol and Norelgestromin)

ESTROGEN AND PROGESTIN COMBO release approx 200 microgram/day of norelgestromin (active metabolite of norgestimate) and 35 microgram per day of ethinyl estradiol (POLYMER MATRIX TDS or monolithic)>> drug release rate is first order (time dependent) however, drug absorption is zero order (time independent) MOA: similar to COC Combination hormonal contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility EDUCATION: one patch is applied weekly for 3 consecutive weeks, followed by 1 patch free week. delivers 200 mg of norelgestromin (the primary active metabolite of norgestimate) and 35 mg of EE daily to the systemic circulation -apply to: abdomen, buttock, upper outer arm, and upper torso ADRS: associated with less breakthrough bleeding and spotting but more breast discomfort or pain, nausea and vomiting and dysmenorrhea PRECAUTIONS: The contraceptive patch may be less effective in women with a body weight more or equal to 90 kg DRUG INTERACTIONS: few have been studied with the patch thus the same ones studied with COC are assumed to apply here as well.

PK of EVRA and NuvaRing and how they differ from COCs? considering the PK differences, suggest one clinical situation when the patch or Ring may (should not ) be recommended over the oral tablets GQ 4

EVRA Absorption: Topical: Equivalent when applied to abdomen, buttock, upper outer arm, and upper torso Ethinyl estradiol and norelgestromin: Rapid; reaches plateau by ~48 hours. Absorption of ethinyl estradiol may be increased with heat exposure due to sauna, whirlpool, or treadmill. Bioavailability: Ethinyl estradiol: ~60% greater using the topical patch when compared to oral tablets. higher exposure of estrogen thus we would expect more side effects NUVARING Duration: Serum levels (contraceptive effectiveness) decrease after 3 weeks of continuous use Absorption: Ethinyl estradiol and etonogestrel: Rapid (Zero order) Tampons do not interfere with absorption. Metabolism: Ethinyl estradiol: Hepatic via CYP3A4; forms metabolites (weak estrogenic activity) Etonogestrel: Hepatic via CYP3A4; forms metabolites (activity not known) Unlike the COCs (which undergo enterohepatic circulation), the patch and the ring bypass first pass metabolism. patch delivers the highest concentration and the COC has the highest variability interms of exposure its patch>COC>ring patch gives more nausea than the ring due to the excess amount of estrogen in the ring. if person has malabsorption syndrome dont give coc oral contraceptives inhibit Cyp450s but induce UDP-glucuronyl transferase

Missed doses of the COC....

If 1 combined oral contraceptive pill or other combined hormonal contraception (CHC) method is missed in the first week of use, back- up contraception or abstinence should be used until the CHC method has been used for 7 consecutive days. In the case of missed CHC in the second or third week of hormones, the hormone-free interval should be eliminated for that cycle. Back-up contraception should be used when 3 or more consecutive doses/days of combined hormonal contraception (CHC) have been missed in the second or third week of hormone use until the CHC has been used for 7 consecutive days. For practical reasons, the scheduled hormone-free interval should be eliminated in these cycles (I RISK for ovulation -higherst risk for ovulation occurs when the hormone free interval is prolonged for more than 7 days, either by delaying the start of CHC or by missing active hormone doses during the first or third weeks of CHC. -ovulation rarely occurs after 7 consecutive days of CHC use. Is EC required? - particualrly when the hormone free interval has exceeded 7 days. >>>>>>>>>>>>EC is rarely indicated for missed CHC in the sec- ond or third week of the cycle unless there are repeated omissions or failure to use back-up contraception after the missed doses (III).>>>>>>>>> whaaaatttt does it mean WHEN IS EC NEEDED: - 1 missed COC in the first week - 3 or more combined oral contraceptive pills missed in the 2nd or 3rd week -1 or more pills missed on Progestin only pill Or when Depo-Provera injection late by 2weeks or more.

Non-oral routes of administration of CHC

Implanon >>> progestin only implanted into the biceps Lunelle >>> combination of estrogen and progestin injection

what are the proposed mechanisms for the interaction between ampicillin and COCs GQ 12 a

LexiComp was used to check for an interaction among ampicillin ad Tri-Cyclen (COC) Results: No action needed to be extra care-full: For short course, use additional method or use another drug. For long course, use another method. Penicillins may diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Concerns generated by anecdotal reports have been refuted by more rigorous scientific and clinical data. > Anecdotal data indicate the possibility that penicillin antibiotics might inhibit the efficacy of hormonal contraceptives. These are almost exclusively related to estrogen-containing products. Thus, the likelyhood that COC will not work is low the bacteria available helps with the concnetration of free estrogen as they help with the hydrolysis of the conjugated estrogens or re-absorption. (enteroheaptic recycling)... this doesn't apply to the progesterone component

Combined Oral Contraceptives (COCs)

MOA: -have multiple due to both the estrogenic and pro-gestational components -main: Combination hormonal contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility SIDE EFFECTS: >common in the first 3 months and are then self limitng. -irregular bleeding -breast tenderness and nausea -weight gain -mood changes -sexual function -headaches RISKS (ACHES) A- abdominal pain: blood clots in pelvis or liver.. tubal pregnancy C- chest pain: blood clots in lungs; heart attack, angina H- Headache: stroke, migraine headaches,blurred vision, high BP E- Eye problems: blurred vision, double vision, loss of vision, blood clots in the eyes, change in the shape of the cornea S- Severe Leg Pain: inflammation and blood clots of a vein in the leg -VTE (COC users have a 2-3 fold increase risk) -stroke and MI : Low-dose combined oral contraceptive pills (containing less than 50 mg of ethinyl estradiol) are not associated with an increased risk of myocardial infarction or cerebrovascular accident in women with no additional risk factors -Breast cancer: There may be a slight increase in breast cancer in cur- rent and/or recent COC users (II-2). The use of COCs in BRCA1/2 carriers is controversial but appears to be associated with a decreased risk of ovarian cancer and no increase in the risk of breast cancer

Progestins used in COCs

Most progestins are 19-nortestosterone derivatives. Pro- gestins may be classified according to their chemical struc- ture as an estrane (norethindrone, norethindrone acetate, ethynodiol diacetate) or as a gonane (LNG, desogestrel, norgestimate) These progestins may also have estrogenic, antiestrogenic, androgenic, antiandrogenic, or antimineralocorticoid activity. > in general the gonane progestins appear to be more potent than the estrane derivatives (smaller doses can be used) > Newer progestins (norgestimate and desogestrel) have little or no androgenic activity, whereas other progestins (cyproterone acetate, drospir- enone, and dienogest) have antiandrogenic activity. >>>>Drospirenone has antiandrogenic activity **All COCs are "progestin-dominant," meaning that the progestin ef- fects on the organs of interest exceed the estrogen component.**

GQ 9 b

Of nine placebo-controlled trials with data for analysis, all showed COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo no big differences among the different COCs and beter than placebo Cochrane review included 31 trials with the following results: 1. A levonorgestrel-COC group had fewer total lesion counts, inflammatory and non-inflammatory lesion counts, and were more likely to have a clinician assessment of clear or almost clear lesions and participant self-assessment of improved acne lesions vs PLACEBO 2.A norethindrone acetate COC had better results for clinician global assessment of no acne to mild acne vs PLACEBO 3.a norgestimate COC showed reduced total lesion counts, reduced inflammatory lesion and comedones counts, and more with clinician assessment of improved acne vs PLACEBO 4. For two combined trials of a drospirenone COC, investigators favoured the despejidone group. In one trial, the drospirenone-COC group showed greater improvement in total lesion count, inflammatory and non-inflammatory lesion counts, and papule and closed comedone counts vs PLACEBO 5. A dienogest-COC group had greater percentage decreases in total lesion count and inflammatory lesion count, and more women assessed with overall improvement of facial acne vs PLACEBO 6.A CMA-COC group had more 'responders,' those with 50% or greater decrease in facial papules and pustules vs PLACEBO 7.COCs that contained chlormadinone acetate or cyproterone acetate improved acne better than levonorgestrel. 8. A COC with cyproterone acetate showed better acne outcomes than one with desogestrel, but the studies produced conflicting results. 9. levonorgestrel showed a slight improvement over desogestrel in acne outcomes, but results were not consistent. 10.A drospirenone COC appeared to be more effective than norgestimate or nomegestrol acetate plus 17β-estradiol but less effective than cyproterone acetate.

Safety concerns with Yasmin/Yaz

Recent scientific focus has been placed on estimating the risk of VTE associated with the use of drospirenone (DRSP), i.e. Yaz & Yasmin, relative to older progestins. Small, observed differences in VTE risk have been reported among different progestins, suggesting the estimated risk may be slightly higher with DRSP compared to levonorgestrel. Drospirenone is frequently referred to as a 4th generation progestin. It is the first synthetic progestin not derived from a sex hormone. Instead, it is chemically related to spironolactone and possesses antimineralocorticoid and antiandrogenic activity DRSP containing CHCs should not be used in women with renal, hepatic or adrenal insufficiency. When used in combination with other medications that may ↑K+ (e.g. ACEi, ARB, NSAID), serum levels should be checked during the first treatment cycle.

different transdermal delivery systems (TDDs)

TDDSs may be categorized into two types, monolithic and membrane- controlled systems. Monolithic systems incorporate a drug matrix layer between the backing and the frontal layers (Fig. 11.3). The drug-matrix layer is composed of a polymeric material in which the drug is dis- persed. The polymer matrix controls the rate at which the drug is released for percutaneous absorption Most TDDSs are designed to contain an excess of drug and thus have drug-releasing capacity beyond the time frame recommended for replacement. This ensures continuous drug availability and absorption as used TDDSs are replaced on schedule with fresh ones. EVRA: first order drug release (time dependent) and zero order drug absorption (time independent) Membrane-controlled transdermal systems are designed to contain a drug reservoir, or pouch, usually in liquid or gel form, a rate- controlling membrane, and backing, adhesive, and protecting layers Membrane- controlled systems have the advantage over monolithic systems in that as long as the drug solution in the reservoir remains saturated, the release rate of drug through the controlling membrane remains constant zero order drug release (time independent) the rate of drug transport in all TDDSs, monolithic and membrane, is controlled by either artificial or natural (skin) membranes. EVRA patch is monolithic

LOLO

ULTRA LOW DOSE COC (EE 10 mcg, Norethindrone 1 mg) - Extnded Cycle COC - LOLO provides a regimen consisting of 24 blue estrogen-progestin tablets, 2 white estrogen-only tablets, and 2 lilac placebo tablets. The patient is instructed to begin taking LOLO on either Day 1 of menstruation (Day 1 Start) or the first Sunday after the onset of menstruation (Sunday Start). If menstruation begins on a Sunday, the first tablet (blue) is taken that day. One blue tablet should be taken daily for 24 consecutive days followed by one white tablet for 2 consecutive days, followed by one lilac tablet daily for 2 consecutive days.

Extended or continuous use of COC

Use of extended cycles (with planned hormone-free intervals) or continuous use of combined hormonal contraceptives (CHC) such as pills, rings or patches without a hormone-free interval may provide patients with relief from severe dysmenorrhea, heavy flow or socially undesirable flow. This can be achieved with products marketed for extended use (84 active tablets and 7 placebo tablets) or by the use of any pill, patch or ring in a continuous regimen (users take no break in between packages). Hormone-free intervals between cycles of any length should not exceed 7 days. Compared with a 28-day cycle, extended cycles or continuous use of CHCs results in fewer bleeding days, decreased likelihood of side effects (e.g., pelvic pain, headache, bloating, swelling and tenderness) and helps improve symptoms of endometriosis and polycystic ovary syndrome. One of the side effects or disadvantages of extended/continuous use is irregular unscheduled bleeding. If an inadvertent pregnancy occurs (due to several missed pills or forgotten change of patch or ring), a woman may not realize she is pregnant without the amenorrhea that might otherwise alert a cyclic contraception user that she could be pregnant.

Extended or Continuous use of CHCs

Use of extended cycles (with planned hormone-free intervals) or continuous use of combined hormonal contraceptives (CHC) such as pills, rings or patches without a hormone-free interval may provide patients with relief from severe dysmenorrhea, heavy flow or socially undesirable flow.[37] This can be achieved with products marketed for extended use (84 active tablets and 7 placebo tablets) or by the use of any pill, patch or ring in a continuous regimen (users take no break in between packages). Hormone-free intervals between cycles of any length should not exceed 7 days. Compared with a 28-day cycle, extended cycles or continuous use of CHCs results in fewer bleeding days, decreased likelihood of side effects (e.g., pelvic pain, headache, bloating, swelling and tenderness) and helps improve symptoms of endometriosis and polycystic ovary syndrome.[37] One of the side effects or disadvantages of extended/continuous use is irregular unscheduled bleeding. If an inadvertent pregnancy occurs (due to several missed pills or forgotten change of patch or ring), a woman may not realize she is pregnant without the amenorrhea that might otherwise alert a cyclic contraception user that she could be pregnant.

St Johns Wort Interactions

consider therapy modification for people taking COC and St.Johns wort. St John's Wort may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers)..... estrogen derivatives are CYP3A4 substrates A report describes several cases of breakthrough bleeding that occurred in patients receiving concomitant oral contraceptives and St John's wort.

Stopping menstruation while on vacation.... (triphasic and biphasic pills) GQ 10 + GQ 11

delay period by a week or a month (skiping the hormone free interval) may be achieved with COCs (monophasic, multiphasic or extended cycle), patch and the ring -21/7 vs 42/7 vs 84/7 regimens (CHEeeeeeeck thissss) -no differences are noted in safety or efficacy... more studies are needed

Fish Oil interactions

no interactions were found between fish oil and Aleese aleese may decerase the absorption of fatty acids

male contraceptives

not as effective as femlae contraceptives due to associated ADRS. (altered male sexual response and male infertility) in the future.... -reversible inhibition of sperm under guidance (injected into vasdeferens which kills sperms and lasts for 10 years.) (reversible) -hormone combiantion (progestin to block testosterone needed to create sperm (testosterone replacement) -vitamin A (it is needed to make sperm thus various ways could be used to block this)