Estrogen is a group of hormones in the body (estradiol, estrone, estriol) that are the primary female sex hormones. Estrogens are responsible for the development and regulation of the female reproductive system. Still, they also play critical roles in the health of other systems, including the heart and vasculature, bone, the vulva and vagina, and the brain (that is, maintaining stable mood and ability to think clearly and remember things). Estradiol (E2) is the body's most common and potent estrogen.  Estrone (E1) is another crucial estrogen with powerful effects primarily because it is converted to estradiol in the body. 

Estrogen therapy (ET) is available in many different forms and dosages by prescription. Typically, ET includes estradiol, although sometimes it includes estrone (a precursor molecule that causes your body to make its estradiol) or estriol. When the uterus has been removed (bilateral oophorectomy WITH hysterectomy), estrogen can be taken alone. When the uterus remains, estrogen must be taken along with a progestogen to prevent cancer of the uterus.

When you have both ovaries removed (bilateral oophorectomy/surgical menopause), you remove your body’s primary source of estrogen, and your estrogen levels will plummet lower than in natural menopause. These extremely low levels of estrogen are thought to be the leading cause of both bothersome menopausal symptoms and long-term health risks in surgical menopause. Thankfully, taking estrogen in surgical menopause reduces both.

Following a bilateral oophorectomy (which involves the removal of both ovaries), the patient immediately enters surgical menopause, meaning they become postmenopausal right away. While there are some similarities between natural and surgical menopause, the need for estrogen therapy is significantly greater in surgical menopause, and typical guidelines for HRT often do not apply in this context. This occurs because, compared to natural menopause, surgical menopause results in a more rapid decline in hormone levels and lower overall hormone levels in the long term.

The ultra-low levels of estrogen in surgical menopause can cause bothersome menopausal symptoms. Still, more importantly, they can reduce the length and quality of your lifespan by increasing the risk of various severe health conditions. We will address each below. 

How long does estrogen take to work? Estrogen therapy can take up to two weeks to work, and temporary side effects can take several months to dissipate (although some can be persistent!). We recommend tracking your symptoms and side effects daily (or at least weekly) to have a clear visual of how symptoms are responding and whether side effects are decreasing over time. 

Similarly, any changes made to your therapy route, dosage, or frequency should be noted in your daily/weekly tracking document/app so that the pattern of change can be monitored objectively. We recommend waiting at least one month on the new therapy before evaluating it or making any additional changes, since effectiveness and side effects may fluctuate before stabilizing again on the latest treatment. 

This is particularly important for those who have an emotional hormone sensitivity; studies suggest that any change in hormone levels can provoke symptoms among those patients, but those symptoms go away again after one month of the new therapy. Therefore, patience and support are needed to evaluate the “true” effects of any treatment change.

Several expert guidelines for hormone therapy in premature menopause (ACOG-POI; ACOG-young POI, BMS-POI) recommend starting with the use of transdermal or oral estradiol therapy to mimic the natural pre-menopausal state as closely as possible. However, a variety of other routes are available. Existing studies indicate that all estrogens (except locally-acting vaginal estrogen products) are effective for protecting against health risks and managing bothersome menopause symptoms.  

The two most common (and recommended) forms of hormone therapy are transdermal estradiol (patches or pills) and oral micronized estradiol.

Transdermal Estradiol (estrogen that is delivered by applying it to the skin in either a gel or patch form).

Expert guidelines for the management of premature menopause (ACOG-POI; ACOG-young POI, ACOG-Prescribing for POI; BMS-POI) recommend beginning with transdermal estradiol because it has a more positive impact on clotting factors, lipids, inflammation, and blood pressure (which may improve safety if continued after the typical age at menopause (i.e., 51)). The transdermal route is especially recommended for those who have an elevated risk of blood clot due to other risk factors (most notably an elevated BMI or smoking). Transdermal estradiol is available in patches placed on the hip or buttocks (USA or UK), or gels placed on the arms (primarily UK). Some evidence suggests that the gel produces fewer local skin irritations than the patch. 

Oral Micronized Estradiol (an estrogen delivered through oral consumption of a pill or tablet).

Estrogen is available in many different pill forms; however, the most commonly used preparation is oral micronized estradiol. Among women and AFAB individuals who are in natural menopause, there is evidence that, relative to transdermal approaches, oral estradiol is associated with greater increases in risk for blood clots and unhealthy lipid changes. However, the absolute risks remain small, and oral estradiol is a safe option for those in surgical menopause if transdermal methods are not tolerated.