What is hormonal suppression?
If your pelvic pain worsens around menstrual cycles or ovulation, hormonal suppression may be an extremely helpful strategy to reduce pain exacerbations.
There are many different hormonal suppression methods, including combined hormonal (contain both estrogen and progestin) pills, combined hormonal ring, combined hormonal patch, progestin pills, progestin intrauterine device (IUD), or gonadotropin-releasing hormone (GnRH) analogues.
There is no single hormonal therapy method that has been proven to be best for patients with dysmenorrhea or endometriosis. The best option for you is the one that manages your symptoms most effectively with the fewest side effects. You may need to try a few different methods to find the one works best for you. Some people even find that using two methods at the same time, such as a progestin IUD plus a continuous combined hormonal pill, is more likely to decrease pain and suppress menstrual periods. Your health care provider can help you navigate these options.
How does hormonal suppression work?
In the Endometriosis and Painful Periods module, we used the analogy that estrogen acts like fertilizer for endometrium (tissue that lines the uterine cavity) and endometriosis, whereas progesterone acts like a lawnmower. The level of estrogen is naturally quite a bit higher than the level of progesterone during most of the menstrual cycle. When endometriosis is present, the natural estrogen to progesterone ratio allows for growth and activity of endometriosis lesions. Using hormonal suppression to switch the ratio to one that is higher in progesterone compared to estrogen is a very effective strategy to suppress endometriosis.
Most currently available medical treatments for abnormal uterine bleeding, dysmenorrhea, and endometriosis work primarily by altering the estrogen to progesterone ratio or by reducing overall estrogen levels, with the goal of minimizing growth and activity of endometriosis lesions. Some of these work by simply adding progesterone (more “lawnmower” effect to make the lesions less active). Others, like combined hormonal pills, suppress the natural estrogen surge that occurs during ovulation (less “fertilizer” effect).
Let’s dive a little deeper into this idea of suppressing the natural estrogen level by using medication that contains estrogen, as this initially seems counterintuitive. All of the reproductive hormones are regulated by a feedback loop. In other words, there is a small area in the brain called the pituitary that sends hormone signals called FSH (follicle stimulating hormone) and LH (luteinizing hormone) to the ovary. FSH and LH tell the ovary to prepare a follicle (small cyst that contains an egg) and ovulate (release the egg). Leading up to ovulation, the ovary makes a lot of estrogen, with the goal of prepping the endometrial lining to have a fertilized egg implant (which is when pregnancy occurs). After the egg is released, the part of the ovary that was housing and preparing the egg switches from making estrogen to making progesterone. The pituitary gland is constantly monitoring the level of estrogen and progesterone in the body. When estrogen and progesterone reach a certain level, the pituitary releases less FSH and LH so that the ovary is not overstimulated. In other words, estrogen and progesterone have a “negative feedback” effect on the pituitary. Hormonal suppression uses this feedback loop. When the pituitary senses the estrogen and progesterone from hormonal suppression, it releases less FSH and LH. Therefore, the ovary does not go through the estrogen surge leading up ovulation. Thus, the total estrogen level in the body stays at a lower, steady amount when using hormonal suppression with estrogen compared to the natural, shifting levels when not using suppression. Progesterone-only methods will have some feedback effect on the pituitary, but the feedback loop is more sensitive to estrogen than to progesterone. Oral contraceptive pills, which contain both estrogen and progesterone, are the most reliable way to prevent the estrogen surge and ovulation.
All of these hormonal medications can significantly reduce the various pelvic pain symptoms associated with dysmenorrhea and endometriosis, but also reduce or eliminate menstrual bleeding that often exacerbates pelvic pain. Many of these methods can be used “continuously” to eliminate menstrual periods. Remember that most endometriosis lesions are thought to form because of retrograde menstruation, so minimizing or eliminating menstrual periods is thought to decrease formation of new endometriosis lesions.
Like all treatments for endometriosis, medical treatments for endometriosis do not cure endometriosis, but they can help decrease pain, minimize menstrual bleeding, and may prevent progression of endometriosis. Because these medications suppress but do not cure endometriosis, recurrence of endometriosis symptoms is common after stopping these medications for an extended period of time. Thus, hormonal suppression is considered an important part of a long-term treatment plan for endometriosis.
What are the types of hormonal suppression?
Combined hormonal methods contain both estrogen and progestin (the term to describe synthetic progesterone). This category includes combined hormonal pills, vaginal ring, or patch. These methods can be used cyclically to have a lighter, less painful period each month or continuously to eliminate menstrual periods.
Progestin-only methods are similarly effective and are available as pills, intrauterine devices (IUDs), implants, or injections. Progestin-only pills are typically taken continuously and usually eliminate menstrual periods. In this category, they are the most likely method to prevent ovulation but not as reliably as combined hormonal pills. Progestin IUDs have also been shown to reduce endometriosis pain and size of endometriosis implants. About 20-30% of people have no menstrual bleeding with progestin IUDs, but most people continue to have some menstrual bleeding with progestin IUDs which can range from irregular spotting to a regular menstrual period. It is important to note that progestin IUDs do not consistently prevent ovulation and may not effectively reduce ovarian cyst formation. Thus, this may not be an adequate option for women with ovarian endometriosis cysts (chocolate cysts). Similarly, progestin implants may reduce overall amount of menstrual bleeding, but typically do not prevent ovulation. Progestin injections have variable effect on menstrual bleeding, with some people reporting no bleeding and others experiencing regular or irregular bleeding.
GnRH analogues are highly efficacious but are considered second line due to less tolerable side effects and increased cost. This category of medications includes GnRH agonists and GnRH antagonists. The most commonly used GnRH agonist is given as an injection every 1-3 months. There is also an GnRH antagonist available as a daily pill. GnRH analogues work differently than combined hormonal methods and progestin-only methods. Rather than using estrogen or progesterone as “negative feedback” on the pituitary, GnRH analogues prevent the pituitary from releasing FSH or LH, which means that the ovaries do not get the signal to make estrogen or progesterone. Because GnRH analogues are associated with greater estrogen suppression than combined hormonal methods and progestin-only methods, they usually cause menopause symptoms including hot flushes, night sweats, and vaginal dryness. There is also a risk of irreversible bone loss when these medications are given for longer than their approved duration. GnRH agonists can be used with low levels of add-back estrogen/progestin therapy, which alleviates these side effects and prevents bone loss, without reducing their efficacy in improving pelvic pain. Add-back therapy with GnRH antagonists is currently under investigation.
Fertility and hormonal suppression
It is important to note that all of these methods function as contraceptives, which prevent pregnancy. Thus, these are not appropriate options for those who are actively trying to become pregnant. However, the impact on fertility is temporary and there is no evidence that any of these methods increases long-term risk for infertility. Some methods are very quickly reversible and natural fertility returns to baseline within a month or two of stopping use. Other methods suppress natural fertility to a greater extent, so your body may need a few months to completely return to baseline. The short-term impact on natural fertility can also vary from person to person.
In addition, fertility is multifactorial, and factors like maternal age, tubal scarring from endometriosis, and medical conditions like polycystic ovarian syndrome (PCOS) or hypothyroidism have a significant impact on natural fertility. It is important to have open and honest discussions with your health care provider so that they can best help you choose a method that manages your pain symptoms and family planning goals.
Risks
Hormonal suppression is a safe, well-tolerated, extensively studied treatment strategy for abnormal uterine bleeding, dysmenorrhea, and endometriosis.
It is possible to have side effects with any medication. The most common side effect of any type of hormonal suppression is irregular or unpredictable bleeding. This is most common in the first 3-6 months after starting a new method. Your health care provider can discuss strategies to manage or decrease breakthrough bleeding. One of the most common strategies recommended for combined hormonal pills or oral progestins is a 5 day “pill vacation.” This is often a helpful strategy if irregular bleeding is lasting for more than 7 days in a row or becomes heavy (similar to a menstrual period). To do a pill vacation, simply stop taking the oral hormonal suppression for 5 days. This will allow the endometrial lining to shed all at once, rather than falling off in patches (which is the cause of the bleeding). Bleeding will increase during the pill vacation. It is best to restart the pills after 5 days, even if still bleeding. The same strategy applies to the vaginal ring or the patch. Simply remove for 5 days, then replace.
A small percentage of people will experience nausea, headache, bloating, change in stool consistency, or mood changes. In the majority of cases, these side effects are temporary and improve with continued use. However, you should talk to your health care provider if symptoms are severe or significantly impacting quality of life.
Risks associated with hormonal suppression are minimal overall and are typically outweighed by the benefits of improved symptoms. However, your health care provider needs to know if you are breastfeeding, use tobacco, or have a history of blood clots in your leg or lungs, high blood pressure, diabetes, migraine headaches, Lupus, breast cancer, liver disease, heart disease or cardiac issues, stroke. Some of the types of hormonal suppression are not recommended if these conditions are present.