HRT, also known as hormone replacement therapy, is the use of synthetic hormones to mimic traditional sex hormones. The use of estrogen HRT has been foundational and approved as the best form of treatment for transgender people for nearly a century.
Want to know more about HRT? Read about the general basics here or check out advanced information here. Or read about testosterone-based HRT here.
What is Estrogen HRT?
Estrogen is the primary sex hormone that produces “feminine” attributes, such as breast growth and body fat redistribution. Estrogen is prescribed to individuals assigned male at birth as part of their gender transition and monitored by their healthcare team to replicate natural estrogen production levels in cisgender women.
Does estrogen HRT require hormone suppressants?
Actually, no. Anti-androgens are not strictly required, although they are commonly prescribed as part of transfeminine hormone replacement therapy.
Individuals with low natural testosterone levels can be adequately suppressed by estrogen alone through a negative feedback loop. Natural testosterone can also be suppressed by high estrogen levels in estrogen monotherapy, but this is only possible with injectable estrogen.
Combined use of anti-androgens with estrogen provides more effective and reliable results by pushing one’s testosterone levels into a cisgender female range. Many transgender women use anti-androgens such as:
- Spironolactone
- Cyproterone Acetate (CPA)
- Bicalutamide
- GnRH Agonists
Finasteride and dutasteride are also used in feminizing hormone replacement therapy to block dihydrotestosterone (DHT), the primary hormone that causes male-pattern baldness.
Isn’t estrogen also prescribed to cisgender women?
Yes! HRT isn’t just for transgender people and was actually created originally to support cisgender bodies. As humans age, bodies aren’t always able to produce enough sex hormones – so synthetic hormones became commonly used as gender-affirming care to help cisgender women struggling to maintain adequate estrogen levels.
I’ve heard of progesterone hormone therapy. What’s that?
Progesterone is another hormone that some individuals use alongside estrogen. Progesterone is the hormone responsible for pregnancy, the menstrual cycle, and gestation.
There is anecdotal evidence that progesterone improves breast development, body fat redistribution, and mood – but there isn’t much official research supporting its use.
Estrogen HRT Methods
There are multiple standard ways to use estrogen for HRT. The chosen administration method depends on:
- Personal convenience
- Lifestyle
- Side effects
- Hormone stability
- Insurance concerns
| Method | Frequency | Stabilty | Pros | Cons |
|---|---|---|---|---|
| Oral | 1x per day | Very stable | No needles, consistent levels | High upkeep |
| Topical | 1x per day | Very stable | No needles, consistent levels | High upkeep, transfer risk |
| Injectable | 1x per week, two weeks, or four weeks | Peaks and troughs | Flexible dosing | Hormone fluctuations, needles |
| Pellet | 1x per three to six months | Moderate fluctuation | Very low maintenance | Hard to access |
| Nasal | 1x per day | Stable | Minimal transfer risk | High upkeep, expensive |
Oral Estrogen
Pill-based and sublingual estrogen is the most common hormone therapy route for transgender women and nonbinary individuals. Typically prescribed as 17-β estradiol, oral estrogen is swallowed or dissolved under the tongue once per day. Examples of oral estrogen include Premarin, Estrace, and Estratab.
Oral estrogen is the most accessible and cheapest form, costing around $10 to $30 per month out-of-pocket. Like topical and nasal therapies, oral estrogen provides extremely stable hormone levels due to daily upkeep.
Unlike oral testosterone, oral estrogen is completely safe to use long-term. Oral testosterone is toxic to the liver, but estrogen is considered cardioprotective despite slight clotting risk.
Need help paying for prescriptions that insurance won’t cover? Try GoodRx.
Topical Estrogen
Estrogen can be safely administered via dermal contact via gels, patches, and creams. Transdermal estrogen is applied daily in small doses and absorbed by the body throughout the day.
The largest disadvantage to topical estrogen is its transdermal nature. You must ensure your hands are completely washed after application to ensure estrogen does not transfer to other humans or animals. Avoid skin-to-skin contact on the application site even after it has dried. Additionally, be mindful of swimming, showering, or applying other creams (ex. sunscreen) on the application site since it will wash or dilute the medication.
Hormone Stability and Pharmacokinetics
Pharmacokinetics refers to the effects of the body based on the original administration of a dose, including when it is eliminated and the time for the next dose.
Since bodies assigned male at birth cannot produce sufficient estrogen naturally, regular administration is required to maintain proper hormone levels. The main disadvantage of injectable and implant/pellet hormones is the pharmacokinetic cycle that causes hormonal dips and peaks. In contact, administration routes such as oral and topical circumvent this by being topped off each day.
Is topical estrogen less effective than injections or oral?
No. Empirical evidence shows that topical estrogen is just as effective as other routes. This myth is due to anecdotal accounts where users post their results (or lack thereof) online, creating the illusion that topical HRT is less effective.
The effectiveness of HRT is determined by hormone levels and genetics, not the administration route. When undergoing hormone replacement therapy, a healthcare professional will monitor your hormone levels and adjust your prescription as needed.
In other words, your provider is going to make sure you obtain optimal hormone levels regardless of whether you use oral, topical, or injectable estrogen.
If you’re intentionally seeking less noticeable or slower results from estrogen, that’s also an option – but you’ll need to find a provider that is knowledgeable in low-dose hormone replacement therapy since it is not the norm. Again, the administration route doesn’t matter; lesser or slower results are caused by a lower estrogen dose for a finite amount of time.
Injectable Estrogen
Estradiol injections typically come as estradiol valerate (Deletrogen) and estradiol cypionate (Depo-Estradiol). Medication is self-administered via syringe once per week, although this can vary to every other week, every three weeks, or monthly, depending on prescription and personal preference.
Since estrogen can be safely administered via tablet, injectable estrogen is less common among transgender women compared to transgender men. Injectable estrogen is usually preferred when high doses are necessary that oral medication can’t accommodate.
Injectable estrogen comes in two forms.
Intramuscular Injections
Intramuscular injections, also known as IM, use long, thick needles to inject estrogen into muscle tissue. Needles range from 1” to 1.5” and 21 to 23 gauge. Needle length varies based on individual need – the needle must be long enough to puncture the muscle layer.
That’s a huge needle! Doesn’t that hurt?!
Actually, IM hurt way less than they look. The needle is visually terrifying, but the size doesn’t cause any additional pain compared to subcutaneous injections.
Pain is primarily caused when the needle breaks the skin barrier and activates nerves to notify your body of injury. Once the skin barrier is broken, the needle continues to penetrate down into the fat and muscle layers – but neither of those contains nerve endings that cause pain.
IM injections are performed on select locations, such as the butt and thigh, since they have plenty of muscle mass. The only complicating factor that may cause additional pain during IM is if you hit a vein. If you do, pull the needle out and try the injection again with a fresh needle and injection site.
Subcutaneous Injections
Subcutaneous, also known as subq, shots use smaller needles to inject estrogen into the subcutaneous fat layer just beneath the skin. Since subcutaneous injections only penetrate the upper two layers, they don’t require the length associated with IM.
Subq injections are compatible with self-injectors like Xyosted, a medical pen that delivers medication via a spring mechanism. While IM can be accomplished with self-injectors, it’s difficult and less common compared to subq.
Both IM and subq injections are meant to be self-administered, although it is possible to find a provider or family member to help if you struggle with needle phobia. Since subq uses smaller needles, many people find them easier to manage.
As noted with intramuscular injections, the pain associated with subcutaneous shots will be similar since pain is largely induced by breaking the skin barrier.
Never reuse needles. Make sure you’re disposing of used needles correctly and find a needle exchange program near you.
Subcutaneous Estrogen Pellets
Pellets are a relatively new form of hormone replacement therapy where crystalline estrogen is implanted beneath the skin by a healthcare professional every three to six months.
Estrogen pellets are exceptionally small (about the size of a single grain of rice) and are inserted under local anesthesia. Unlike other forms of HRT, where medication is typically self-administered, pellets must be administered by a provider.
Similar to IM and subq injections, estrogen pellets will suffer the same dips and peaks due to their pharmacokinetics. They provide immense convenience since you only have to worry about the application every few months, but you’ll have starker estrogen dips.
Pellets sound cool! Why haven’t I heard more about them?
Probably because they’re hard to access. Oral and injectable estrogens are the standard forms of HRT, so you have to go out of your way to request pellets.
Just because a healthcare provider prescribes HRT doesn’t mean they’re knowledgeable or comfortable with pellets – so you’ll have to find a provider that specializes in it.
Nasal Estrogen
Nasal estrogen, such as Evamist, is administered once per day and functions the same as topical estrogen. However, nasal estrogen significantly reduces the risk of accidental transfer.
Due to how new nasal estrogen is, it is rare to find. As of the time of this article, there are no generic versions available in the United States.
Frequently Asked Questions (FAQ)
Is estrogen safe to use long-term?
Yes. Long-term use of estrogen is generally considered safe, but only under the supervision of a healthcare professional to ensure your hormone levels are optimal.
There are lots of scary articles out there that claim transgender-related HRT is dangerous. Studies show HRT is safe, although there is a lack of high-quality, long-term data to assess limitations in previous studies, since long-term studies require… time.
Estrogen does impact your health, but not in any particularly scary way. Metabolic changes and risk of blood clots increase, BUT these changes place transgender women at the same exact risk as cisgender women with naturally occurring estrogen.
Does brand name matter, or will using generic medication cause inferior results?
No. Pharmaceutical companies will say otherwise, but brand name does not impact HRT effectiveness. The only thing that matters is the active ingredients and dosage.
Does injectable estrogen cause faster results than other forms of HRT?
No. Accounts that injectable estrogen is more effective are entirely anecdotal and not aligned with empirical evidence. Effectiveness of estrogen is determined by dose and HRT level, not administration route.
When will I see the effects of HRT?
That depends on dosage and genetics. Some changes, such as skin and mood changes, occur quickly, while other changes can happen years down the line. Look at the women in your family and consider how puberty impacted them to predict how HRT will manifest changes.
Read my basic guide to HRT for information on effects and timelines.