Gonadal Hormones and Inhibitors Flashcards
Natural Estrogens
Estradiol- major secretory product of the ovary
Estrone, Estriol - liver or peripheral tissues
Pregnant Mare urine - “Premarin”
Synthetic Estrogens
Steroidal- ethinyl estradiol, mestranol, quinestrol
Non-steroidal- diethylstilbesterol, chlorotrianisene. methallenestril
Estrogens:
MOA
Bound to alpha-2 globulin (sex hormone binding globulin - SHBG and albumin)
Estrogen Absorption, Metabolism, Excretion
Well absorbed oral (effect of food insignificant)
Metabolized in liver - high ratio of hepatic to peripheral effects (increased production of clotting factor)
Renal excretion
Clinical Uses for Estrogens
- Primary hypogonadism (failure to develop ovaries, premature menopause, castration, menopause)
- Postmenopausal hormonal therapy (prevention of osteoporosis (maintain bone density), vasomotor symptoms, sleep disturbances, atrophic vaginitis)
- Ovulation suppression in patients with severe dysmenorrhea
- Treatment of hirsutism and amenorrhea secondary to excessive androgen production by the ovary
- Combination Contraception (cycle control)
- Male to female transition
Adverse Effects of Estrogen
- Uterine bleeding
- Breast cancer (post menopausal, short term therapy more acceptable)
- Endometrial cancer (post menopausal)
- Nausea, Breast tenderness, bloating, HA
- Depression, mood disturbances
- Thrombosis
- Heart disease, HTN, MI
Natural and Synthetic Progestins
Natural: Progesterone
Synthetic: Hydroxyprogesterone Medroxyprogesterone Megestrol acetate Desogestrel Norethynodrel Norethyndrone Levonorgestrel
Progestins Pharmacokinetics
Rapidly absorbed, short half-life
Metabolized in the liver
High first-pass metabolism
Bioavailability = 10-15% (food increases)
Which Progestins do not have androgenic activity:
Desogestrel (Mircette, Desogen), Norgestimate (Ortho-Cyclen, etc)
What is Progesterone’s effect on insulin?
Increases basal insulin levels and insulin response to glucose: Promotes ketogenesis
Clinical Uses of Progestins
- Hormone replacement
- Contraception
- Prevention of menstruation
- Secondary physiologic amenorrhea
- Delay of premature labor
- Endometrial hyperplasia prophylaxis
- Diagnostic use – test of estrogen secretion
- Adjunct female infertility
- Hyperandrogenism/polycystic ovary syndrome
Adverse Effects of Progesterone
- Nausea
- Headache
- Sleep disorder, fatigue
- Breast tenderness
- Depression, mood swings
- Thrombosis, CVA, TIA
- Hepatic dysfunction
Is a combo contraceptive a good option for women who are breast feeding? why or why not?
It is not a good option because it will suppress lactation. Some of the drug can go to breast milk but not bad for baby, for those that will have some lactation.
Adverse effects of combination pill
Mild: Nausea (MC), mastalgia, edema Changes in serum proteins and endocrine function Headache, worsening migraine Withdrawal bleeding not occurring (!)
Moderate:
Breakthrough bleeding – progestational agents
Weight gain (if high androgen content, change drug if a problem)
Acne – higher if androgen content is high, lower if estrogen content is high
Ureteral dilatation and increased bacteriuria
Vaginal infections
Amenorrhea
Severe:
Thromboembolism (taken in consideration for all pts, regardless of age,wt,smoke)
MI (higher risk in smokers)
Cerebrovascular disease (highest risk smokers over 35)
GI: cholestatic jaundice, symptomatic gallbladder disease
Depression, mood disturbances
Cancer (questionable HPV/cervical)
Which oral contraceptive is the least effective
Progestin-only “mini” pill
