Postmenopausal Hormone Therapy and Hormonal Contraceptives Flashcards
Postmenopausal Problems
Osteoporosis Urogenital Atrophy Hot Flushes Sweating Disordered Sleeping Mental Issues
Studies of PHRT
Combined PHRT (estogen and progestin)
Increased CV risk + increased risk of breast cancer
Decreased incidence of colon cancer and Alzheimers
Estrogen Monotherapy
Increased risk of stroke and breast cancer
Carcinogenic risk only significantly increased post long term therapy (>5 years)
Treatments Options for PHRT
Systemic: PO or transdermal
Sequential treatment:
estrogen for 2 weeks followed by combo with
progestin for 10 days. Then drug withdrawal for 5
days–> bleeding.
Continuous combined therapy: no artificial cycle
At first breakthrough bleeding may occur
Local (intravaginal)–> th of vaginal dryness
Tibolon: prodrug
Phytoestrogens: no proven clinical efficacy
Hormonal Contraceptives
General Features
Extensive use and high degree of efficacy measured by Peal Index; used by people who are generally fully healthy
Pearl Index: # unwanted pregnancies/100 women in given year
Hormonal Contraceptives
Causes of Inefficacy
Additional Medical Uses
Causes of Inefficacy
Compliance problems
Diarrhoea
Enzyme inducers
Broad Spectrum ABs: estrogen glucuronidate not
cleaved--> no free estrogen
Additional Medical Uses Dysmenorrhea Hypermenorrhea Endometriosis Acne
Hormonal Contraceptives
Preparation Categories
Combined: Estrogen and Progestin
Progestin Only
Emergency: as either one of two above
Hormonal Contraceptives
Combined Preparations
Drugs, Mechanism of Action
Estrogen compound mainly ethinyl estradiol
Progesterone compound: best would be a gonane es gestodene as no androgen activity
Most efficacious: Pearl Index <1
Mechanism of Action
predom. mech: inhibition of ovulation by both compou.
Hypothamus: decrease frequency of GnRH pulses
Pituitary: decrease GnRH responsiveness and direct
FSH and LH secretion inhibition
Additional Mechanisms:
Progestin mainly: increased viscosity of cervical
secretion–> swimmers have harder time
Decreased uterine duct motlity
Estrogens: –> inhibit breakthrough bleeding
Subtypes of Combined Contraceptives
Preparation
Orally Applied
Generations based on amount of ethinyl estradiol used
1st, 2nd, 3rd gen
2nd and 3rd gen are considered low dose
Mono, bi, triphasic and sequental preps: aim to mimic
physiological menstruation
Non Oral Forms of Combined Contraceptives
Transdermal Patch
Vaginal Ring
IM Depot Injection
Orally Combined Contraceptives
Drug Combinations
1st Gen: <50microg ethinyl estradiol + ex levonorgestrel,
norgestrel
2nd Gen: <30microg ethinyl estradiol + ex levonorgestrel,
norgestrel
3rd Gen: <20microg ethinyl estradiol + ex gestrodene,
desogestrel
Combined Contraceptives
Non Contraceptive Benefits
Contraindications
Non Contraceptive Benefits
Menstral Disorders
Improvement of endometriosis
Acne
Decrease risk of ovarian cysts/ benign fibrotic breast di.
Reduced risk of extrauterine pregnancy
Contraindications Intensive smoking; general CV risk factors Age pre epiphyseal closure and >35 Hormone sensitive tumors Hepatic disease Migrane Pregnancy: teratogenic if continued
Combined Contraceptives
Side Effects
General:
Nausea, vomiting, headache, breast tenderness
Water retention, breakthrough bleeding
Acne, weight gain, hirsutism (due to androgenic effects)
Metabolic:
Increased synth of vit K dep clotting factors
Reduction ATIII
Increased plasma TG level
Gall Stone Formation
CV:
Slight increased risk for venous thrombosis when no
other risk factors present, if there are–> large increase
3rd generation has larger increased risk
Increased risk of AMI and stroke when other risk factors
are present
Tumor Risk:
Increased risk: cervical cc in HPV carriers
Increased risk of hepatic adenoma (not malignant)
Progestin Only Contraceptives
General Features
Preparations
General Features:
overall efficacy same as combined contraceptives
Indications:
If estrogen is CI (smoking, <35 years)
Lactation (progestin doesn’t inhibit milk formation)
Compliance problems: long acting depot available
Preps: Minipill SC Implant IM Depot Injection Vaginal Ring IUD
Progestins
Minipill: Drug Names and Characteristics
Norethindrone, Ethynodiol Diacetate, Norgestrel, Levonorgestrel, Desogestrel
Pearl Index: 0.3-3
SE: Breakthrough Bleedings, Acne
Progestins
SC Implant: Drug Names and Characteristics
Levonorgestrel: slow release into circulation for 5-7 years
Ovulation inhibited in only 75%–> additional mechs +
Progestins
IM Depot Injection: Drug Names and Characteristics
Norethindrone Released into circulation for 3 months Special side effects due to very strong - feedback HDL decrease, LDL increase Reduced bone density Sustained infertility nach Absetzten
