Term
|
Definition
estradiol-17
ethinyl estradiol (Estinyl)
conjugated estrogens (Premarin; others) |
|
|
Term
|
Definition
progesterone
norethindrone
medroxyprogesterone
drospirenone |
|
|
Term
|
Definition
Combination estrogen-progestogen oral contraceptives
Progestin only contraceptives |
|
|
Term
|
Definition
Conjugated estrogens
Estrogen replacement therapy (Premarin®)
Hormone replacement therapy (PremPro®) |
|
|
Term
| For emergency contraception |
|
Definition
mefepristone (RU-486)
misoprostol |
|
|
Term
| Selective Estrogen Receptor Modulators |
|
Definition
clomiphene (clomifene; Clomid®; others)
raloxifene (Evista)
tamoxifen (Nolvadex®) |
|
|
Term
|
Definition
anastrozole [Arimidex®]
exemestane [Aromasin®] |
|
|
Term
| Androgen receptor antagonist |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
Primary female sex steroid
Feminizes
Used pharmacologically for contraception, menopausal symptoms, infertility |
|
|
Term
| Progestogens (Progesterone, P) |
|
Definition
Both facilitates and opposes estrogen actions
Used for contraception and to counter undesired effects of estrogens |
|
|
Term
| Androgens (Testosterone, T) |
|
Definition
Primary male sex steroid
Has androgenic (virilizing) and anabolic (growth-promoting) activities |
|
|
Term
|
Definition
Proceeds from Cholesterol
Note the position of the enzyme aromatase.
Many actions of T in men are mediated after conversion to estrogen.
During gestation, masculinization of the fetus is due to activation of estrogen receptors. |
|
|
Term
| Estrone (E1), estradiol (E2) and estriol (E3) |
|
Definition
are in equilibrium in circulation.
E2 is the most potent of the circulating estrogens.
Dihydroepiandosterone (DHEA) sold as anti-aging supplement |
|
|
Term
Examples of
conjugated forms of Progestogens |
|
Definition
megestrol (oral)
hydroxyprogesterone caproate (injection)
medroxyprogesterone acetate (oral or injection) |
|
|
Term
Examples of
synthetic forms of Progestogens |
|
Definition
norgestrel
levonorgestrel
norgestimate
desogestrel
norethindrone |
|
|
Term
|
Definition
Pituitary: regulate the release of LH and FSH
Ovary: stimulate follicular growth
Uterus: stimulate growth and proliferation of non-secretory endometrium
Vagina: change in skin tone
Cervix: increase thin mucus favoring sperm
Development and maintenance of internal and external genitalia
Development and maintenance of female secondary sex characteristics |
|
|
Term
| Non-reproductive Actions of Estrogens |
|
Definition
Bones
maintain calcium content of bones (decreased resorption)
Liver
improve cholesterol profile (increase HDL; decrease LDL; small decrease in total cholesterol, small increase in triglycerides)
Blood
increase coagulation |
|
|
Term
|
Definition
Structure of steroids similar
Steroid receptors similar
There is some “cross-talk” – one kind of steroid may interact with another kind of receptor, especially for synthetic analogs.
Example: gestational diabetes |
|
|
Term
|
Definition
Most are combinations of a synthetic estrogen plus a synthetic or conjugated progesterone.
(eg. ethinyl estradiol + norgestimate)
Blocks LH surge and prevents ovulation
Also changes endometrium and vaginal mucus to reduce fertility
Use for 21 days, with “off” period of 7 days.
But extended treatment options available
99% effective.
Rapidly reversible. Cycles usually reinitiate ovulation in 1-3 mo after cessation. |
|
|
Term
|
Definition
Have 20-35 μg of either ethinyl estradiol or mestranol plus a synthetic or conjugated progesterone in a constant ratio
Doses were higher in the past.
21 hormone containing pills are the same
55 brands/formulations available in US
Most prescribed worldwide |
|
|
Term
| Combination Birth Control Pills |
|
Definition
Biphasic (7 forms) or Triphasic (12 forms)
Have varying ratios of estrogen and progesterone
21 hormone containing pills are NOT the same
Most common in US are triphasics like “Ortho Tri-Cyclen, ” with constant synthetic estrogen and increasing, then decreasing progestin content |
|
|
Term
| Benefits of Oral Contraceptives |
|
Definition
Menstrual
More regular, reduced blood loss, reduced anemia, less pain
Reduced pelvic inflammatory disease
Reduced endometriosis
Reduced ectopic pregnancies |
|
|
Term
| The Down Side of Estrogens |
|
Definition
Rare but serious side effects
Increased risk for
Venous thromboembolism (VTE) or blood clot, especially in smokers
Hypertension
Older preparations increased BP in 5% of women with normal BP and 10-15% of women with previously high BP; newer formulations less but new users still need to be monitored.
Gall bladder disease |
|
|
Term
| “Progesterone” Only Birth Control |
|
Definition
“Mini-pill” – 1 pill daily; no “off” period
Several different preparations containing different progestins in various doses.
Injections - last 12 weeks
Implants - small rods which release slowly
Intra-uterine devices - 1 or 5 year versions |
|
|
Term
| Mechanisms by which progestin only methods prevent pregnancy |
|
Definition
Changes in cervical mucus that are not conducive to sperm
Changes in endometrium that are not conducive to implantation
Less effective at blocking ovulation, but depends on dose.
(Low dose blocks ovulation in 50% of cycles, but high dose preparations may inhibit ovulation up to 99%.) |
|
|
Term
| Contraceptives and cancer risk |
|
Definition
Current consensus is NO INCREASED RISK.
Estrogens stimulate cellular proliferation in many tissues.
Long-standing concern
Some studies show risk, especially with older preparations
Some populations may be more vulnerable.
Risk of breast cancer is increased 30% more in women already at high risk because of BRCA 1 mutation.
Longer duration of use may increase vulnerability.
Newer studies suggest more of a role for progestogens in cancer risk than previously appreciated.
However, weight of the evidence is no increased risk of breast cancer for most women. |
|
|
Term
| Combination contraceptives decrease risk for |
|
Definition
Endometrial carcinoma
Ovarian cancer |
|
|
Term
|
Definition
Can be either combined synthetic estrogen + progestin or progestin only
Should be started as soon as possible after unprotected sex (99% effective if started within 72 hours)
Probable mechanisms to prevent pregnancy:
Prevention or delay of ovulation
Changed rate of tubal transport of ovum
Changes in the endometrium unfavorable to implantation
Induces nausea in 40%.
Sometimes given combined with anti-emetic
Progestin only version supposed to have less |
|
|
Term
|
Definition
Progesterone receptor antagonist (anti-progestin)
Causes endometrial shedding
Typically used in conjunction with a prostaglandin to induce uterine contractions
may be effective up to 50 days after |
|
|
Term
|
Definition
Agents that act as estrogen receptor antagonists
Examples
Clomiphene
Tamoxifen
Raloxifene
BUT agents are not pure antagonists
Mechanism appears due to interactions with estrogen receptor accessory proteins in different tissues |
|
|
Term
| Selective Estrogen Receptor Modulators (SERMs) |
|
Definition
Estrogenic activities are tissue specific
Goal = “good” estrogen effects in bone, brain, liver + no “bad” estrogen effects in breast or endometrium, where proliferation leads to cancer |
|
|
Term
|
Definition
was the first
Antagonist in breast
Used as treatment for breast cancer and as a prophylactic to prevent recurrence
Agonist in non-breast tissue
Beneficial Effects
Bone
Liver
decreased total cholesterol, decreased LDL, no increase HDL
different than estrogen
Adverse Effects
Vasomotor
Increased risk of deep vein thrombosis, stroke
Can cause hot flashes
Endometrium (increased risk of uterine cancer) |
|
|
Term
| Clomiphene = Clomifene (SERM) |
|
Definition
Used for infertility
Typically given for 5 days in follicular phase
Antagonist at the estrogen receptor in the anterior pituitary gonadotrope
Prevents negative feedback of LH and FSH
FSH, LH levels increase; better follicular recruitment; better ovulation
Major side effect is that it works too well: induces multiple ova, resulting in twins or greater multiple births |
|
|
Term
|
Definition
Agonist in bone
Used for osteoporosis
Agonist in liver
Benefits cholesterol balance
different from estrogens (decreased total cholesterol, decreased LDL, no increase HDL)
Agonist for vasomotor symptoms, deep vein thrombosis and stroke
No effects on endometrium
May be antagonist in breast
Current clinical trials for prevention of breast cancer |
|
|
Term
|
Definition
androgen receptor antagonist
Flutamide
Used in prostate cancer |
|
|
Term
|
Definition
Converts androstenedione and testosterone to estrogens (produced primarily by adrenal gland in women)
Also known as cytochrome P450#19 |
|
|
Term
|
Definition
Can reduce estrogen levels
Used for breast cancer
Either as first line treatment
or as second line after tamoxifen
Steroidal vs nonsteroidal
Do not increase risk of uterine cancer or deep vein thrombosis
Can cause hot flashes |
|
|
Term
| Aromatase Inhibitors STEROIDAL |
|
Definition
Exemestane
Substrate analog
Irreversibly inactivates aromatase enzyme as “suicide inhibitor” |
|
|
Term
| Aromatase Inhibitors NONSTEROIDAL |
|
Definition
Anastrozole
Interacts reversibly with heme groups of P450s, including aromatase |
|
|
Term
|
Definition
Inhibit enzyme that converts testosterone to dihydrotestosterone
Used primarily for benign Prostatic hypertrophy
dutasteride (Avodart®)
finasteride (Proscar®; Propecia® for male pattern baldness) |
|
|
Term
|
Definition
Vasomotor instability
Hot flashes, night sweats, or chills
Urogenital atrophy
Vaginal dryness, urinary incontinence
Disrupted sleep
Insomnia, nighttime or early-morning waking
Skin/Soft tissue
Breast atrophy, skin thinning, decreased skin elasticity, formication
Sexual dysfunction
loss of libido
Psychological symptoms
Depression, mood swings, irritability, fatigue
And LATER
Skeletal
Increased risk of osteoporosis |
|
|
Term
|
Definition
Systemic skeletal disease
Low bone mass
Microarchitectural deterioration
Bones more fragile
More susceptible to fracture
Significant medical problem
8 million women, 2 million men in USA
40-50% of women will have osteoporotic bone fracture in life time |
|
|
Term
| Estrogen Replacement Therapy at Menopause |
|
Definition
First thing tried was administration of a low dose of conjugated estrogens (Premarin®), about ½ bioequivalent dose to current combination birth control pills)
Still widely used
Causes increased risk of endometrial cancer in women with a uterus
Must include progestogen to counteract; called HRT (Hormone Replacement Therapy)
Now wide variety of non-oral administration routes |
|
|
Term
|
Definition
Some plants produce substances that have weak estrogenic effects = Phytoestrogens
Used for menopause symptoms
Examples
Soy – genistein
Black cohosh roots
Generally concentration of active ingredient too low to have much effect
Inconsistent
Possibly contaminated
Not regulated
For a drug, must prove safety and efficacy.
For an herbal, FDA must prove it is unsafe for removal from market. |
|
|
Term
| Old Evidence Suggested that HRT Improved Quality of Life |
|
Definition
Menopause Symptoms
Hip and Vertebral Fractures
Skin thinning and loss of elasticity
Tooth Loss
Age-related diseases
Death < Age 80 |
|
|
Term
| Women’s Health Initiative Findings |
|
Definition
Increased risk
Coronary Heart Disease
Invasive breast cancer
Stroke
Venous thromboembolism
Reduced risk
Colorectal cancer
Hip fracture |
|
|
Term
|
Definition
Loss of testosterone with aging is small and inconsistent.
Most men do not require replacement therapy.
Significant side effects
undesired growth of prostate, lack of sperm production, mental changes (rage), others |
|
|
Term
|
Definition
| Primary female sex steroid. Feminizes. Used pharmacologically for contraception, menopausal symptoms, infertility |
|
|
Term
|
Definition
| Both facilitates and opposes estrogen actions. Used for contraception and to counter undesired effects of estrogens |
|
|
Term
|
Definition
| Primary male sex steroid. Has androgenic (virilizing) and anabolic (growth- promoting) activities. |
|
|
