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Dr. Cook’s Guide to Hormone Therapy Treatments for Patients with Pelvic Pain

The typical medical treatment for endometriosis provided by most OB/GYN’s basically is manipulating a woman’s hormones, primarily her estrogen and/or progesterone levels. The concept behind this approach to treatment of endometriosis is that estrogen tends to stimulate the growth of endometriosis and progesterone balances or stabilizes the effect of estrogen. In a very simple example, one can think of estrogen as fertilizer for the lawn and progesterone as the lawn mower. The goal of medical treatment of endometriosis is to increase the ratio of progesterone to estrogen (progesterone only treatment), decrease the amount of both estrogen and progesterone (combinational birth control pills) or to eliminate estrogen from the body (GnRH treatments such as Lupron).

Unfortunately, all of the medical treatment options for endometriosis treatment are fairly crude, commonly with unacceptable side effects. The medical treatments do not provide a cure for the disease, only work for a portion of endometriosis patients and even when the treatment option is effective the results are only temporary. Even use of a GnRH agonist such as Lupron that cause a temporary medical menopause may not be effective in treating endometriosis as the actual lesions of endometriosis can produce their own estrogen and remain active and potentially invasive despite ovarian suppression.

All treatment options using progesterone as the choice of endometriosis treatment are trying to suppress the effect of estrogen on the endometriosis. This endometriosis treatment option can be effective in some women, especially if the patient’s pain is primarily around her period and if she does not tolerate estrogens (nausea, etc.)

The different kinds of progestin (a progestin is a substance that has progesterone like effects on the body) used to treat endometriosis include, bio-identical compounded progesterone creams, a pharmaceutical bio-identical oral micronized progesterone, synthetic progestins, progesterone only birth control pills, Depo-Provera and the Mirena IUD.


Progesterone cream is the most common form of topical progesterone. Non-prescription progesterone creams usually do not have enough progesterone to alter the menstrual cycle. Some women find this low dose of hormone to be effective. Prescription progesterone cream is usually made in a compounding pharmacy at the requested strength of the ordering physician. It can be difficult to get consistent and adequate absorption of progesterone using this delivery method.


Oral Progesterone can include compounded bio-identical progesterone pills, oral micronized progesterone in oil pill (Prometrium), synthetic progestin Aygestin (Norethindrone acetate) or Provera (Medroxyprogesterone) or the progesterone only birth control pill.

The progesterone only birth control pills do not have any estrogen and the amount of progesterone is about 1/3 the dose of progesterone (thus the term mini-pill) found in the average combinational estrogen/progesterone pill.


Depo Provera is a long acting form of progesterone that is given as a shot and lasts for months. The most common side effects include weight gain, break through bleeding and depression.


Use of the Mirena IUD as a treatment option for endometriosis delivers a daily dose of about 20mcg of the progesterone, levonorgestrel. Birth control pills with levonorgestrel contain a daily dose of 90mcg to 150mcg. This is four and a half to seven and a half times the dose of the Mirena IUD. On average women using the Mirena IUD have about a 50% to 90% reduction in their menstrual flow and 20% stop having a period within one year (this is only temporary and periods start again shortly after removal of the Mirena IUD). Every treatment option has drawbacks including the Mirena IUD as 23% of women will have some spotting or bleeding in between their periods, 13% will have abdominal or pelvic pain and 12% ovarian cysts. If you experience significant side effects you may need to have it removed and look at your other options for endometriosis treatment.

Progesterone treatment options for endometriosis treatment

Type of progesterone Brand name Generic name Typical treatment schedule
Bio-identical compounded progesterone cream No brand name (Only available through compounding pharmacy with prescription) Bio-identical progesterone cream Apply to skin once daily
Bio-identical oral micronized progesterone Prometrium Micronized progesterone 100mg tablet by mouth before bed
Synthetic progesterone Aygestin Norethindrone acetate 15mg by mouth once a day. Start at 5mg once a day for 2 weeks, then increase by 2.5mg every 2 weeks
Synthetic progesterone Provera Medroxyprogesterone One tablet once a day
Progesterone only birth control pills Camila Norethindrone 0.35mg One tablet once a day
Progesterone only birth control pills Errin Norethindrone 0.35mg One tablet once a day
Progesterone only birth control pills Heather Norethindrone 0.35mg One tablet once a day
Progesterone only birth control pills Jolivette Norethindrone 0.35mg One tablet once a day
Progesterone only birth control pills Nora-BE Norethindrone 0.35mg One tablet once a day
Progesterone only birth control pills Nor-QD Norethindrone 0.35mg One tablet once a day
Progesterone only birth control pills Ortho Micronor Norethindrone 0.35mg One tablet once a day
Long acting progesterone shot Depo-Provera Medroxyprogesterone acetate One shot every three months
Progesterone IUD Mirena IUD Levonorgestrel intrauterine device Change every 5 years
Dose of progesterone is equivalent to levonorgestrel 20mcg each day
Different types of progestin and associated characteristics used for endometriosis treatment
Generation of Progestin 1st
Progesterone Activity LOW
Estrogen Activity Slight
Relative Androgen Activity >Gen #3
Advantages May improve cholesterol (lower LDL, raise HDL)
Generation of Progestin 1st
Progesterone Activity LOW
Estrogen Activity Slight
Relative Androgen Activity >Gen #3
Advantages May cause less nausea, fluid retention or migraines
Generation of Progestin 1st
Progesterone Activity MEDIUM
Estrogen Activity Slight
Relative Androgen Activity >Gen #3
Drawbacks Higher risk of breakthrough bleeding
Generation of Progestin 2nd
Progesterone Activity HIGH
Estrogen Activity
Relative Androgen Activity >Gen #1
Drawbacks May increase bad cholesterol (LDL) and decrease good cholesterol (HDL)
Advantages 1. Used in FDA approved extended birth control pills such as Seasonique and Seasonale
2. Most commonly used progesterone
Generation of Progestin 2nd
Progesterone Activity HIGH
Estrogen Activity ANTI-E
Relative Androgen Activity >Gen #1
Drawbacks May increase bad cholesterol (LDL) and decrease good cholesterol (HDL)
Generation of Progestin 3rd
Progesterone Activity HIGH
Estrogen Activity MINIMAL
Relative Androgen Activity LOWEST
Drawbacks May have higher risk of blood clots than other progestins
Advantages 1. Can increase good cholesterol (HDL)
2. May have less weight gain, effect on metabolism and risk of acne
Generation of Progestin 3rd
Progesterone Activity HIGH
Estrogen Activity SLIGHT
Relative Androgen Activity LOWEST
Advantages 1. Minimal effect on cholesterol and carbohydrate metabolism
2. FDA approved for treating acne
3. Lower risk of nausea and vomiting risk than other birth control pills
Generation of Progestin 4th
Progesterone Activity HIGH
Estrogen Activity SLIGHT
Relative Androgen Activity LOWEST
Drawbacks Can increase potassium levels – do not use if liver, kidney or adrenal disease
Advantages 1. Lessen PMS associated water retention and moodiness
2. FDA approved to treat Premenstrual Mood Disorder (PMDD) and acne

Combined Estrogen & Progesterone Treatment Options

Combinational birth control pills (contain both estrogen and progesterone) are commonly the first step in treating patients with endometriosis, pelvic pain and painful periods. If most of the pain a woman is experiencing is around her period then reducing the intensity of pain and/or the frequency of periods with the use of birth control pills may be an effective endometriosis treatment in some patients. With cyclic use of birth controls pills for treatment of endometriosis associated menstrual cramps, the period is often lighter with decreased pain. Some women can take the pill continuously (skipping the sugar pills each month and taking hormone pills every day without a break,) either completely avoiding periods or significantly reducing the number of periods over time (for example 4 periods a year instead of 12 periods a year).

Even though this endometriosis treatment involves actually taking estrogen and progesterone, women taking a combinational birth control every day actually experience a significant reduction in the amount of estrogen and progesterone in their body. At first this may not make sense but the ovaries make a lot more estrogen than that found in the pill. The small consistent does of estrogen and progesterone in the pill is enough to signal the ovaries not to make estrogen, temporarily turning the ovaries off and eliminating their relatively large release of estrogen. Less estrogen in the body as a result of the pill can result in less stimulation and activity of the endometriosis. Periods are usually shorter and lighter on the pill because there is less stimulation and growth of the endometrium (inside lining of the uterus that sloughs off during menstruation).

The most common treatment option in this category is the standard combinational estrogen/progesterone birth control pill. Other forms of combinational estrogen/progesterone treatment include the Nuvaring and the Ortho-Evra patch. The patch, however, delivers about 50% more estrogen than a standard 35mcg birth control pill and thus is not the best for endometriosis treatment.

If your doctor prescribes a particular birth control pill as treatment to help with your endometriosis symptoms hopefully it will work well without any side effects. In these cases you have found a good treatment option for your endometriosis (note, while the treatment may manage your symptoms it does not eradicate the disease).

Unfortunately, the pill does not always work well or patients may have significant side effects. In these cases a different birth control pill may work better, but there are so many birth control pills on the market it can be confusing trying to decide which option is right for you. Not all birth control pills are the same. Understanding these differences will help you and your doctor choose the best birth control pill option to treat your endometriosis symptoms while minimizing the side effects you may experience.

The difference in the various pills really comes down to a couple of things including the amount of estrogen, the type and amount of progestin and the balance or relative amount (ratio) of estrogen and progesterone. The type of estrogen is the same in virtually all of the combinational birth control pills (Ethinyl Estradiol). The amount of this estrogen in the pill can vary from 10 micrograms (micrograms=mcg) to 35mcg. The combinational pill has one of eight types of progestin (substance with progesterone like activity). The types of progestin in the pill include norgestimate, desogestrel, norethindrone, norethindrone acetate, ethynodiol diacetate, drospirenone, levonogestrel, and norgestrel. Nuvaring has a different progestin than found in any pill and is called etonogestrel.

Side effects

If you have any significant side effects (nausea, decreased sex drive, not feeling well, etc.) with this treatment option, using a pill with a different type of progestin or estrogen dose may work better for you. One of the more common side effects patients experience is break through bleeding, that is bleeding in between the normal period time. This is often associated with cramping and pain. Birth control pills in part provide an effective option for endometriosis treatment by eliminating or reducing the number of bleeding and pain days. Often bleeding in between the period is a result of either the wrong overall estrogen level or the ratio of estrogen and progestin. There are over 100 different brands of combinational birth control pills. If the pill your doctor has given you as the best treatment option for your endometriosis but you still have cramping and bleeding, find your pill on the tables below. Perhaps even make a copy and take it with you to your next doctors appointment and see if there might me a better birth control pill option for your endometriosis treatment. A pill with a different estrogen level, different type of progestin or different ratio of estrogen and progestin may be a better option for managing your pelvic pain.

Break Through Bleeding (BTB) and continued pain while taking BCP

There are many causes of BTB on the pill and your OB/GYN should be able to help resolve this for you. One of the many possible contributing factors to your BTB can be a dominance of either estrogen or progesterone. When your doctor preforms a transvaginal ultrasound he or she will be able to measure the thickness of the endometrium (the inner lining of the uterus). BTB can be the result from the lining of the uterus being either too thick or too thin. If you are on the pill, changing the balance of the estrogen and progestin in the pill may help.

If endometrium is thin on sonogram (<5) one treatment option is to switch to a higher estrogen pill (or less progestin) and or higher estrogen to progestin ratio pill. If endometrium is thick on sonogram (>5) one treatment option is to switch to a lower amount of estrogen in the pill and/or a pill with a lower estrogen to progestin ratio or a progestin only pill.

Estrogen/Progesterone combinational OCP treatment options for endometriosis treatment by type of progestin

Danazol (Danocrine) Treatment Option

Danazol was approved in 1976 by the Food and Drug Administration (FDA) as the first medication specifically for treatment of endometriosis. It is a synthetic hormone and there is nothing natural about this treatment option. It is a cross between progesterone and testosterone. If a woman with endometriosis has severe pain around the time of her period and only minimal pain during the rest of the month, then stopping her period can be a very effective treatment option. Unfortunately a significant percentage of women will continue to have a period even when taking the birth control pill continuously (skipping the “sugar pills” and taking the hormones pills without a break). Danocrine can be an effective treatment option, as it usually will stop a woman’s period while taking this medication. This treatment option also has several potential significant drawbacks including the possibility of acne, oily skin, extra hair growth and deepening voice. These are uncommon and the medication can be stopped immediately if any of these are noticed. This medication has to be taken two to three times a day, which can be both an advantage and disadvantage. In the case of significant side effects, danazol is rapidly excreted from the body, enabling rapid alleviation of side-effects following discontinuation. Consistently taking any medication three times a day is certainly a disadvantage and challenging.

GnRH (Lupron, Synarel) Treatment Option

Patients with severe endometriosis pain are often offered the treatment options by their OBGYNs: Lupron, coagulation of endometriosis at surgery or hysterectomy (with or without removal of the ovaries). Lupron is one medication in a class of drugs known as GnRH agonists. GnRH stands for Gonadotropin Releasing Hormone. Agonist means the medication activates the same cellular receptors as the natural hormone. Gonadotropin Releasing Hormone is normally released by a part of the brain called the hypothalamus. It is released in little boluses at a specific interval. This in turn stimulates the pituitary gland at the base of the brain to release FSH (follicle stimulating hormone) into the blood stream, which stimulates the ovaries to both mature an egg and produce estrogen. A GnRH agonist temporarily shuts down the ovaries’ production of estrogen. At first it might seem counter-intuitive that giving a medication that does the same thing as the natural hormone can have the very opposite effect. The GnRH agonist, however, is released continuously, not episodically like the natural hormone. Continuous stimulation of the hypothalamus by the GnRH agonist shuts down the release of FSH and thus the ovaries. As soon as the Lupron wears off the episodic release of Gonadotropin Releasing Hormone resumes, as do ovulation and the ovarian production of estrogen.

Estrogen stimulates the growth of endometriosis. Since Lupron stops the ovaries from producing estrogen, this medical therapy results in a temporary medical menopause creating a low estrogen environment in the body. Without estrogen from the ovaries it was thought endometriosis would be inactivated. Even under the best circumstances the pain relief provided by this treatment is temporary. There are, however, several significant problems with the use of GnRH agonists for endometriosis treatment. First, it may not work. Endometriosis can produce its own estrogen and in these cases Lupron will not suppress the endometriosis activity or pain. In more advanced cases of endometriosis, even if the Lupron suppresses the endometrial implant activity, it does nothing for the pain caused by scaring and fibrosis resulting from the invasive endometriosis.

The side effects with GnRH endometriosis treatment can be severe. Some of the more common side effects include, hot flashes, night sweats, moodiness and irritability, nausea, insomnia, and possibly mental fog to name a few. One also has to be concerned about risk of bone loss and this is the reason this drug is only approved for 6 months of use. There may be indications for prolonged use, but add back therapy and bone density surveillance are usually part of the treatment protocol.

The standard approach by the vast majority of doctors is to start a patient on this treatment with a long acting form of GnRH agonist such as Depo Lupron, which lasts one to three months depending on the dose given.

It just does not make sense to me to start a long acting form of a treatment that offers no chance of a cure, but rather just helps relieve symptoms temporarily and has a fairly high chance of severe unacceptable side effects. Why not start out with a short acting GnRH agonist such as Synarel? This is a nose spray that is given twice a day. If this is a good option for endometriosis treatment with minimal side effects for any given individual, then she can switch over to a long acting form such as the one or three month Depo Lupron shot. If the patient has significant side effects, the nose spray can be stopped and the effects of the drug will wear off fairly quickly.

I think part of the frustration with many patients who have had a bad experience with Lupron are related to the prolonged time for the side effects to wear off. The other complaint I hear a lot is that of patients feeling mislead by their doctors telling them it would help their pain without any significant side effects.

Aromatase Enzyme Inhibitors (Letrazol, Femara, Arimidex) Treatment Option

Aromatase enzyme converts a precursor hormone to estrogen. Blocking aromatase enzyme prevents estrogen production anywhere in the body, potentially including the endometriosis implant itself. Examples of Aromatase Enzyme Inhibitors include Letrazol, Femara and Arimidex. Unfortunately this group of medications as a treatment option for endometriosis does not provide a cure, if effective is temporary, can have the same severe side effects including significant bone loss experienced with GnRH agonists (Lupron) and does not successfully treat all endometriosis related pain.

Dr. Cook’s Guide to Hormone Therapy Treatments for Patients with Pelvic Pain
Article Name
Dr. Cook’s Guide to Hormone Therapy Treatments for Patients with Pelvic Pain
The typical medical treatment for endometriosis provided by most OB/GYN’s basically is manipulating a woman’s hormones, primarily her estrogen and/or progesterone levels.

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  1. My doctor prescribed megestrol acetate to contol heavy menstal bleeding.
    I have had a history of endometreosis, plus removal of one ovary and one fallopian tube.
    What are natural supplament options instead of synthetic progesterone. What can i do naturally that is most effective?