Therapeutics of Estrogens/Progestins Flashcards
At what age does menopause most often occur naturally?
45-55 years
What causes menopause?
The woman’s body stops ovulating, so estrogen levels drop significantly. The negative feedback of estrogen in the HPO axis is halted, so FSH levels rise sharply as well.
How long must a woman go from her last period until the diagnosis of menopause?
12 consecutive months
Name and describe the 3 stages surrounding menopause.
premenopausal: endocrine changes that occur leading up to menopause
perimenopause: endocrine changes that occur surrounding menopause, symptoms often occur starting here
postmenopause: endocrine changes after cessation of menstruation
When do the worst symptoms of menopause occur?
usually during the first 1-2 years, but sx overall can occur for 7 or more years
Describe the effect of estrogen/progesterone on the HPO axis, and the effects of high/low levels.
Estrogen and progesterone provide negative feedback (mediated by inhibin) on the hypothalamus and the anterior pituitary. When levels are low, as in menopause, the body tries to compensate by increasing GnRH, FSH, and LH as negative feedback is lost.
What factors affect the age of onset of menopause?
(1) genetics
(2) ethnicity
(3) smoking
(4) hysterectomy with ovarian conservation
clinical presentation of menopause
vasomotor sx (most common–hot flashes/night sweats)
irregular menses
mood changes
sleep disturbances
episodic amenorrhea
genitourinary syndrome (vulvovag. atrophy, dryness, dyspareunia)
What are the long-term consequences of menopause?
CV dx bone loss osteoarthritis skin changes (wrinkles) balance issues change in body composition
When is hormonal therapy indicated in menopausal women?
severe vasomotor sx, vulvovaginal atrophy, osteoporosis prevention
What are the absolute contraindications of hormone replacement therapy?
clotting disorders unexplained vaginal bleeding liver disease estrogen dependent malignancies (endometrial/breast cancer) stroke pregnancy
What is the main principle guiding estrogen monotherapy?
ONLY indicated for women without a uterus (no uterus -> do not have to worry about endometrial cancer)
In estrogen/progestin combination therapy, what dosage forms of estrogen that do not require a progestin component?
topical products, low dose patches, Estring - stay relatively local, systemic exposure not great enough to warrant progestin
What is the difference between Estring and Femring?
Femring has a higher level of estrogen, and therefore may require a progestin component, at least temporarily. Estring has a low enough estrogen dose that a progestin is not required.
“A ring is bigger than a string.”
What is the general guideline for use of oral/transdermal estrogen use? Topical?
prescribe at the lowest dose for the shortest period of time for relief of vasomotor sx
topical exclusively for women experiencing vulvovaginal atrophy
Women with an intact uterus require what in order to protect from risk of endometrial cancer/hyperplasia?
progestin
Describe the results of the Women’s Health Initiative Study (in terms of number of CV events, cancers, and fractures).
Combo therapy resulted in increased CV events and breast cancers. There were, however, lower numbers of colorectal cancers and fractures. In estrogen monotherapy, there were increased strokes and VTEs. Heart attacks and cancers were not changed significantly. Fractures were still decreased.
Both studies demonstrated that there was no protection from cognitive impairment.
What was the result of the extended post-intervention phase of the WHI? What recommendations came from these results?
The increased risk of these adverse effects from HRT depend on the age of initiation and the time since menopause. Thus, HRT is recommended only in women less then 60 y.o. and within 10 years of menopause with no evidence of CHD. Women outside 10 years of menopause are at an increased risk of CHD within the first two years of therapy. Women aged 70-79 and >20 years menopausal are at the highest risk. Women with previous CHD attain no additional protection from events with HRT.
What was the ELITE trial designed to test?
the time-dependance of postmenopausal HRT. Women were divided into groups (within 6 years of MP, outside 10 years).
What were the results of the ELITE trial?
Evidence showed that initiation of HRT within 6 years of menopause provided some protective effect, but not after 10 years of MP.
What are the four types of estrogen/progestin combination therapies?
continuous cyclic, continuous long cycle, continuous combined, and intermittent combined
Describe continuous cyclic hormone combination therapy.
Estrogen given daily, progestin given for at least 12-14 days every month. (Premphase and combipatch)
How often will women on continuous long cycle therapy have a period?
every other month when progestin component is given
What is one major concern with both continuous cyclic and continuous long cycle therapy?
both carry an increased risk of developing endometrial cancer
