Microdosing Estrogen: Risks and Benefits

What is Estrogen?

Estrogen is a group of female sex hormones that play a crucial role in the development and regulation of the female reproductive system and secondary sexual characteristics. These hormones are primarily produced in the ovaries, but they can also be produced or converted into forms of estrogen in other places, such as fat tissue, adrenal glands, liver, and breasts [1, 2].

There are several types of estrogen hormones, each playing a significant role at different stages of a woman's life. The three main types are estradiol, estrone, and estriol. Estradiol is the most common estrogen and the primary estrogen in women of childbearing age, produced in the ovaries. It is involved in menstruation, notably the thickening of the lining. It can, however, also lead to gynecological problems, including endometriosis and cancers in the reproductive system[1, 2].

On the other hand, Estrone is primarily produced by the adrenal glands and can also be found in post-menopausal women. Estriol is an estrogen elevated during pregnancy; only trace amounts are found in women outside of pregnancy [2].

Uses of Estrogen Hormone Therapy

Estrogen can be taken through oral estrogen contraceptives, which usually contain the compound ethinyl estradiol. It can also be taken through tablets combined with progestins or an intra-vaginal ring or skin patch [3, 4]. The doses will vary from 0.5mg per day to 1.5 mg, depending on the condition for which you take estrogen supplements.

Estrogens are also primarily used in hormone replacement therapy and hormonal contraception. In feminizing hormone therapy, estrogen therapy can promote breast growth and the development of female secondary sex characteristics. It would be used in conjunction with testosterone blockers, which suppress natural testosterone and facial hair growth and help people transition their gender identity.

Postmenopausal women may be prescribed estrogen supplements to minimize side effects, such as hot flushes, sweating, and bone loss induced by menopause. Men with prostate cancer can be prescribed estrogen as a palliative treatment [4].

Side Effects of Estrogen

Estrogen is a critical female reproductive hormone kept in a tight homeostatic balance. Therefore, manipulating your body's natural levels will likely lead to physical changes and side effects. For taking synthetic forms of estrogens, the side effects include: 

• breast tenderness, nausea, vomiting, bloating, stomach cramps, headaches, vaginal itching, weight gain and increased body fat, hyperpigmentation of the skin, hair loss, unusual bleeding from the uterus, and anaphylaxis.

If you are taking estrogen supplements, make sure to monitor your symptoms and seek help from your medical provider if you experience subtle changes relating to the symptoms above.

What is Microdosing?

Microdosing refers to the practice of consuming very small, sub-clinical doses of substances, often encountered in psychedelic drug settings. It has become popular in recent years because it is seen as a way of getting the benefits of psychedelic drugs, such as enhanced creativity, sociability, focus, and connection, without the hallucinogenic effects [5, 6].

The substances most commonly used for microdosing are psychedelic substances like lysergic acid diethylamide (LSD) and psilocybin-containing mushrooms. A microdose is typically 10%  to 20%  of a standard dose but can be titrated more accurately based on your experience [6, 7].

It's essential to note that microdosing isn't limited to psychedelic substances. Regardless of the substance used, the practice involves taking these small doses of a drug, often in regular intervals [6, 8]. In our previous blog on microdosing Adderall, we discussed the uses of microdosing in clinical trials to study the biokinetics of a drug and microdosing GLP-1 agonists, which can help achieve better blood sugar regulation.

Microdosing Estrogen

Microdosing estrogen is a relevant concept when thinking about estrogen supplementation. After all, microdosing can overcome some of the side effects of a drug. However, it is essential to establish what form of estrogen you are microdosing on and why you supplement it. 

Microdosing refers to taking hormone replacement therapy (HRT) at lower doses. This approach is often used by individuals who may not want the full effects of traditional HRT, such as nonbinary or gender-nonconforming people [9]. 

When to Microdose Estrogen and Why

Microdosing estrogen can be particularly beneficial for alleviating symptoms of menopause. Clinical trials have shown that low-dose estrogens can reduce hot flashes by an average of 65%. It also prevents bone loss in early menopause, with one study showing an increase of 2.6% for the femoral neck, 3.6% for the hip, 2.8% for the spine, and 1.2% for the body [10, 11]. It can also reduce vasomotor symptoms of menopause, such as heart disease and heart attacks, and compliance of patients with the therapy regimen. One study showed an 86% reduction in vasomotor symptoms compared to a 55% reduction in patients on placebo, demonstrating that starting with low doses of estrogen and increasing only if necessary is a viable treatment option [12]. 

Microdosing estrogen can also be used in women of childbearing age either as a contraceptive or to treat amenorrhea - irregular or absent periods. Low-dose estrogen in these cases may produce fewer side effects and may, therefore, be less disruptive for these women [13].

In feminizing hormone therapy, microdosing estrogen may be a more subtle way for trans women to transition into their woman identity. The microdoses of estrogen slow down the onset of female secondary sexual characteristics, such as breast development, giving the individual time to get used to them. It also enables the body to get used to higher estrogen levels and gradually reduces testosterone levels, which can lead to body fat redistribution [14].

Risks of Microdosing Estrogen

While microdosing estrogen has benefits, it's essential to be aware of potential risks.

• Some studies suggest that the decrease in hot flashes with low-dose estrogens, ranging from 60-70%, is less than the 80-90% reduction with standard dosing [15, 16]. This means that a significant proportion of menopausal women may not find sufficient relief from symptoms with low-dose estrogen. However, 60-70% will.
• Although low-dose estrogen can prevent bone loss, the effect is dose-dependent. This indicates that microdosing estrogen may not stop bone loss as much as a full dose of estrogen therapy would [16]. 
• The side effects of full estrogen doses are still present in low-dose estrogen therapy.

Lastly, while low-dose estrogen has been associated with fewer side effects such as vaginal bleeding or breast tenderness, it's important to note that serious adverse effects, such as breast cancer, linked with traditional doses of estrogens may not be averted entirely with lower-dose preparations [15]. 

Microdosing Testosterone

Microdosing testosterone is distinct from micordosing estrogen but may be used to address gender dysphoria by supplementing the male sex hormones. Like estrogen, microdosing testosterone can make the gender transition smoother. A previous blog on microdosing trenbolone addresses this topic in more detail.

Summary: Microdosing Estrogen

In conclusion, microdosing estrogen can offer benefits such as reduced menopausal symptoms and increased bone density. However, the microdose may not be sufficient to facilitate all the effects of estrogen replacement therapy, therefore it is best to discuss your estrogen therapy with a health care professional.