Estrogen – The Good, the Bad and the Ugly

Categories: Hormone Replacement

Estrogen is an essential hormone that has over 400 actions on a woman’s body. It’s what defines a woman. It’s been in your body since you were born and increases greatly at the time of puberty. It’s easy to take it for granted when everything is working automatically. When a young woman’s menstrual periods become irregular, painful or accompanied by severe mood swings, anxiety, depression or acne, that’s an indication of a system that’s gone awry. Birth control periods or Depo-Provera are a bad, ugly way to treat these problems. When prescribed, they do little to correct the underlying problem. These signs and symptoms are the way the body communicates to you that it needs help. A better approach is to determine the root cause that’s driving the problem.

Estrogen and You

At menopause, when estrogen levels drop to zero, the body goes into a relative state of shock because it’s missing an essential hormone that’s been present in your body since puberty. The severity of the symptoms depends on how abruptly the estrogen levels drop. The most suffering occurs when a young woman in her thirties or forties, undergoes a total hysterectomy with removal of both ovaries. Overnight, her estrogen drops to zero leading to severe insomnia, profuse hot flashes/sweats and brain fog all of which lead to a transformational state of severe dysfunction. When a woman goes through natural menopause, it occurs gradually and the woman has a chance to adjust to a gradual decline in estrogen. With the latter, symptoms may not be as disabling. However, both women eventually are at risk for the effects of estrogen deprivation: premature aging, dementia, heart disease, osteoporosis and a poor quality of life. If you have the ability to prevent or reduce the risk of these conditions, why would you choose to deny yourself?


When estrogen is given to a menopausal woman, one needs to be respectful of the normal physiology. Giving estrogen in a topical delivery system that’s applied to the skin is the safest route of administration. Giving excessive doses of estrogen with injections or pellets is associated with increased and unwanted side effects.

Estrogen whether it’s made by your body or taken as medication, eventually must be processed by your liver. The liver serves as a clearinghouse for all hormones or medications. In the liver estrogen is processed by a chemical reaction called hydroxylation. There are two versions of hydroxylation: 2-hydroxylation and 16-hydroxylation. Most of the beneficial actions of estrogen occur by way of 2-hydroxylation metabolites. We call this the “good” estrogen. While some of the 16-hydroxylation metabolites benefit the bones, when present in excess, they are associated with an increased risk of hormonal related cancers. Of course, this is not the only cause of breast/ovarian cancer, but it’s one that can usually be corrected. An excess of 16-hydroxylation products can also contribute to mood swings and PMS. That’s why the 16-hydroxyation metabolites are called the “bad” estrogen. We routinely monitor the 2/16 ratio to optimize estrogen actions and reduce risks.

2/16 Ratio

Lifestyle measures that improve the 2/16 balance are exercise and a healthy diet that includes cruciferous vegetables like broccoli, cauliflower, kale, Brussel sprouts and cabbage. For women who don’t get enough of these vegetables or who have a very low 2/16 ratio, we can supplement them with nonprescription supplements of diindolemethane (DIM) or indole-3-carbinol (I3C). Recent studies in the cardiology literature show when the 2-hydroxylation byproducts undergo another chemical reaction in the body called methylation, they’re converted to 2-methoxyestradiol that protects against heart disease and has an anti-cancer effect. Methylation can be enhanced with nonprescription supplements including vitamin B12, folic acid, zinc resveratrol, N-acetylcysteine, trimethylglycine and S-adenosyl-methionine.
I would advise against any of these dietary supplements unless you’re working with a knowledgeable professional who can monitor your levels and advise you on appropriate doses of these products. For menopausal women on estrogen replacement, I routinely monitor estrogen metabolites at least once a year. With correction of the 2/16 ratio, women often report less breast tenderness and PMS. It also provides us with another modality for monitoring safety and enhancing the full benefits of the estrogen.

For More Information

For more information on the 2/16 ratio, read page 120 of my book, “Outliving Your Ovaries: An Endocrinologist Reviews the Risks and Rewards of Treating Menopause With Hormone Replacement Therapy.” Since every woman goes through menopause, reading this book empowers you with information on how best to manage menopause.

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