AssessmentsEstrogens and antiestrogens
Estrogens and antiestrogens
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 65-year-old woman comes to the hospital for radical mastectomy of the right breast with reconstruction. She was diagnosed with estrogen receptor positive breast cancer of the right breast. The left breast is conserved. Because of concern for recurrence in her other breast, she is prescribed adjuvant therapy with tamoxifen. Which of the following best describes the mechanism of action of this medication?
Content Reviewers:Yifan Xiao, MD
Contributors:Sam Gillespie, BSc, Maria Emfietzoglou, MD, Salma Ladhani, MD, Elizabeth Nixon-Shapiro, MSMI, CMI
Now, antiestrogens, or estrogen antagonists include full antagonists, which antagonize natural estrogens in all tissues, and selective estrogen receptor modulators, or SERMs, which act as estrogen antagonists in some tissues but also act as estrogen agonists in others.
But first let’s talk a bit about natural estrogen, which plays a big role in the menstrual cycle.
The hypothalamus, which is part of the brain, secretes gonadotropin-releasing hormone, or GnRH, which travels to the nearby pituitary gland and stimulates it to secrete two hormones follicle stimulating hormone, or FSH, and luteinizing hormone, or LH.
These hormones gradually increase during the first 2 weeks of the cycle, called the follicular phase, but estrogen is the main hormone synthesized during this phase.
The high estrogen levels also make the pituitary more sensitive to the actions of hypothalamic GnRH, acting as a positive feedback signal, and at the end of the follicular phase, it leads to a massive surge of FSH and LH that leads to ovulation where one of the follicles releases an ovocyte.
Okay, now the 2 weeks following ovulation is called the luteal phase, where the follicle that released the oocyte becomes the corpus luteum.
This structure mainly synthesizes progesterone which helps maintain the uterine lining so a fertilized oocyte can implant.
Other than the menstrual cycle, estrogen along with progesterone are also responsible for the maturation of the female reproductive organs during fetal development.
Estrogens are also responsible for the development of female secondary sex characteristics during puberty, like the growth of breasts and widening of the hips, as well as distribution of fat on the buttocks, hips, and thighs.
Alright, now estrogens also act on a systemic level.
They have a protective effect on the cardiovascular system by keeping the blood vessels’ walls flexible, and by lowering the levels of LDL-cholesterol.
So, they help sustain bone density.
The bad news is that during menopause, which usually happens around age 50, the ovaries run out of functional ovarian follicles.
They can be given orally, via transdermal patches, vaginal creams, or intramuscular injection.
Okay, now synthetic estrogens have various indications.
First, they are used for primary hypogonadism, or primary gonadal dysfunction, in which low gonadal activity leads to low levels of estrogen in the body, resulting in delayed puberty, or delayed sexual maturation.
So, synthetic estrogens can stimulate the development of secondary sexual characteristics and accelerate growth.
They’re also indicated for primary amenorrhea where menses fails to occur by the age of 16 in the presence of normal growth and secondary sexual characteristics.
In this case, synthetic estrogens can be given cyclically to mimic the natural menstrual cycle and trigger menses.
Another indication is estrogen deficiency resulting from surgical removal of the ovaries or from premature ovarian failure, where the ovaries stop ovulating and producing hormones before the age of 40.
Estrogens are also indicated as hormonal contraceptives along with a progestogen.
Alright, now let’s move on to side effects which include vaginal bleeding, nausea, and breast tenderness.
There is also an increased risk for endometrial cancer when given without progesterone to counteract their effects on the endometrium, as well as a small increase in the risk for breast cancer.
Finally, a super important side effect of diethylstilbestrol is that females that were exposed to DES in utero, meaning that they are daughters of women who were treated with DES during pregnancy, can develop vaginal adenosis, and clear cell adenocarcinoma, which is a type of vaginal cancer.
Okay, next we have antiestrogens.
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