When we talk about female hormonal drugs, the biggest treatments that come to mind are for breast cancer, menopause, contraceptives, and fertility.
As estrogen often causes breast cancer to grow, breast cancer can be treated with hormonal drugs. There are two major ways to tackle breast cancer via hormonal therapy. One, you can either suppress breast cancer’s response to estrogen, or two, you can prevent estrogen from being made. With the first method, we can use a group of drugs called Selective Estrogen Receptor Modulators, or SERMs. The two main types of SERM drugs are Tamoxifen and Raloxifene. They are called “selective” because they act differently on estrogen receptors in different parts of the body. Tamoxifen acts as an agonist on estrogen receptors in bone and lipid, but acts as an antagonist in breast and partial agonist in the endometrium. Being a partial agonist means that the drug can bind to estrogen receptors, but its effects are only partially as strong as that of normal estrogen. Because of this property, they essentially act as antagonists in the presence of estrogen, and agonist in the absence (or with low level) of estrogen. And so while Tamoxifen block estrogen response in the breast, tackling breast cancer, being a partial agonist in the endometrium means the patients taking tamoxifen increase their risk of getting endometrial cancer.
On the other hand, Raloxifene acts as an agonist on estrogen receptors in bone and lipid, and as an antagonist in both breast and endometrium, and therefore tackles breast cancer without the risk of developing endometrial cancer. Raloxifene is known best as a treatment for osteoporosis, as it stimulates bone growth by acting as an agonist on estrogen receptors on the bone.
So far we’ve been talking about treating breast cancer by suppressing the cancer’s response to estrogen. However, we can also tackle the problem by preventing estrogen from being made altogether. Estrogen is made via an enzyme called aromatase, which converts androgens into estrogens. By using drugs that inhibit aromatase, we can inhibit estrogen synthesis in all tissues of the body. These aromatase inhibitor drugs are Anastrozole, Letrozole, and Exemestane. With no estrogen around, there is no increased risk of uterine cancer or thrombosis.
Estrogen therapy can be used for many reasons. Perhaps some women naturally do not secrete enough estrogen, like in the case of Turner Syndrome, and take estrogen to make up for what they do not have. Others take estrogen or synthetic estrogen drugs to make up for the loss of estrogen seen after menopause. Particularly, estrogens tell bones to grow, which is great for preventing osteoporosis often found in post-menopausal women. Estrogen, of course, causes breast cancer to grow, so don’t use estrogen if you have had breast cancer or are at risk for breast cancer. Also as I mentioned above, estrogen has a positive effect on uterus, which has lots of estrogen receptors, telling it to grow. Therefore, taking lots of estrogen drugs can cause hyperplasia of the uterus, and therefore increases the risk for uterine cancer. Because of this, post-menopausal women taking estrogen also take progestin to counterbalance this effect. In a normal pre-menopausal woman, progestin (i.e. progesterone) normally puts a cap on the effects of estrogen by down-regulating estrogen receptors and increasing enzymes that degrade estrogen after it reaches a certain level. This lets the endometrium maintain a certain thickness that is optimal for the egg to implant. Taking progestin along with estrogen for the hormonal replacement therapy in menopausal women has the same effect — to put a cap on the estrogen-induced uterine hyperplasia, and therefore preventing the risks of uterine cancer.
Some examples of progestin drugs include progesterone, progestogen, norethindrone, norgestrel, levonorgestrel, desogestrel, etonogestrel, drospirenone, and medroxyprogesterone acetate (MPA).
There are two ways to prevent pregnancy using hormones: either by using an estrogen/progestin combo or using just plain progestins. Normally in the body during the menstrual cycle, when there is too much estrogen, the estrogen gives a negative feedback on the hypothalamus, telling it to stop making Gonadotropin-releasing hormone (GnRH). Without GnRH, you can’t tell your anterior pituitary to secrete FSH or LH. Without FSH, you can’t stimulate your follicles to grow. Without LH, you can’t ovulate. And therefore, you can’t release an egg and get pregnant. Therefore, estrogen drugs like Premarin, Ethynyl Estradiol, or Mestranol act as contraceptives. However, as I mentioned above, estrogen can cause endometrial hyperplasia, causing an increased risk of endometrial (uterine) cancer. Therefore estrogen contraceptives are almost always combined with progestins to counterbalance the effects of estrogen on endometrial hyperplasia.
Progestin-only drugs can also be used for contraceptives. Although progestins help in making your uterus an ideal environment to implant the egg, like estrogen, it also has a negative feedback effect on the hypothalamus and pituitary, decreasing the release of FSH and LH. In normal physiology, the progesterone you produce at high levels during pregnancy prevents you from menstruating while you are pregnant. With this same reason, taking high levels of progesterone when you are not pregnant will prevent you from menstruating and ovulating, preventing you from getting pregnant. As progestins downregulates estrogen, which of course makes your skin nice and lady-like, taking progestin can cause increased acne and hirsutism (you become hairy), as well as increase LDL (“bad cholesterol”). The one exception is a progestin by the name of Desogestrel, which does everything a progestin would do, except increase acne or hirsutism.
Progestins remember also play a role in the proliferation of mammary glands, so if you want to breastfeed, using progestin-only contraceptives are more fitting for your goals. Estrogen can also induce your body to make more clotting factors which increases the risk of thrombosis, and therefore if you are a woman at risk of thrombosis and want to be on contraceptives, better use a progestin-only drug.
Finally, a big issue many people worry, both men and women, is infertility. There are many reasons why one may be infertile, but since I’m talking about hormones now, I’ll talk about the treatment for anovulatory infertility, a special type of infertility in which not enough GnRH is released (and therefore not enough FSH and LH is released) even though the patient may have functional hypothalamus, pituitary, and ovaries, and normal estrogen production. So what drug do you use? Clomiphene, otherwise known as “The Fertility Pill.” It is an all-around estrogen receptor antagonist. If you block the estrogen receptor, then estrogen can’t bind to the receptor, and therefore it can’t have negative feedback on GnRH release from the hypothalamus. GnRH therefore becomes “unblocked,” releasing LH and FSH, causing your follicles to mature and ovulate, and therefore restoring fertility. However, too much can cause you
to become “too fertile,” increasing the chances for multiple births. You know those articles you see in the newspapers about the women who had sextuplets or octuplets? Yes, those are probably due to Clomiphene.
Clomiphene, like most drugs out there, isn’t without its side effects. Since you are essentially making estrogen useless, simulating the effect of having decreased estrogen, you’ll experience hot flashes, similar to menopausal women who also have decreasing estrogen.