Hormones 101: Estrogen, Testosterone & Anti-Androgens

What Are Hormones?

Hormones are chemical messengers in your body. They travel through your bloodstream and tell cells what to do — like "grow breast tissue" or "produce sperm".

For trans feminine HRT, we focus on four main players:

1. Estrogen — the primary feminising hormone
2. Testosterone — the primary masculinising hormone we want to reduce
3. Anti-androgens — blockers that reduce testosterone's effects
4. Progesterone — an optional further feminising hormone

Estrogen

Estrogen is the primary female sex hormone. It is responsible for:

• Breast development
• Fat distribution to hips, thighs, and face
• Skin softening
• Slowing body and facial hair growth
• Regulating menstrual cycles in cisgender women

In trans women, we take estradiol — the main biologically active form of endogenous estrogen — to bring levels into a cisgender female range.

The Estradiol Molecule

Estradiol's chemical formula is C₁₈H₂₄O₂ (molar mass: 272.38 g/mol). Like all steroid hormones, it is built on a four-ring backbone: three six-membered cyclohexane rings (A, B, C) fused to one five-membered cyclopentane ring (D) — the cyclopentanoperhydrophenanthrene skeleton. Key features:

• Ring A is aromatic (benzene-like), shown with a dashed circle
• –OH at C3 on ring A (a phenol group, due to the aromatic ring)
• –OH at C17β on ring D
• –CH₃ at C13 (carbon-18), the C/D ring junction

How Estrogen Works

Estradiol enters cells and binds to estrogen receptors (ERα and ERβ), activating genes that drive feminine physical development. It also:

• Lowers LH and FSH — reducing testosterone production in the testes via negative feedback on the HPG axis
• Increases SHBG (sex hormone-binding globulin) — which binds to remaining free testosterone, making it hormonally inactive
• Promotes breast duct growth — the first step in breast development

Testosterone

Testosterone is the primary male sex hormone. In trans women, we want to lower its levels or block its effects, because it:

• Stimulates facial and body hair growth
• Deepens the voice (a permanent change; HRT cannot reverse it)
• Increases muscle mass and bone density
• Promotes male pattern hair loss

The Testosterone Molecule

Testosterone's chemical formula is C₁₉H₂₈O₂ (molar mass: 288.42 g/mol). It shares the same four-ring steroid backbone as estradiol — three six-membered rings and one five-membered ring — but differs in key functional groups: it has a ketone (=O) at position 3 on ring A instead of a hydroxyl group, and an extra methyl carbon giving it 19 carbons vs estradiol's 18.

The Aromatase Connection

Your body contains an enzyme called aromatase that can convert testosterone into estradiol. This is why:

• Some people assigned male at birth naturally have measurable estradiol levels
• Even at low testosterone levels, some conversion to estradiol may occur in trans women

The goal of HRT is not just to convert T into E, but to actively suppress T production and block its effects — hence why anti-androgens are used alongside estradiol.

Anti-Androgens (Testosterone Blockers)

Anti-androgens stop testosterone from working. There are two main approaches:

Type	How it works	Examples
Receptor blockers	Bind to androgen receptors, preventing T from activating them	Bicalutamide, Spironolactone (partial)
Production suppressors	Reduce the testes' testosterone output via the HPG axis	Cyproterone acetate, GnRH agonists

The HPG Axis

To understand how anti-androgens and estrogen suppress testosterone, you need to know the hypothalamus–pituitary–gonadal (HPG) axis:

1. The hypothalamus releases GnRH (gonadotropin-releasing hormone)
2. The pituitary gland responds by releasing LH and FSH
3. The testes produce testosterone in response to LH

Estrogen disrupts this loop via negative feedback — high estradiol signals the hypothalamus and pituitary to reduce LH and FSH output, which in turn lowers testosterone production. GnRH agonists work differently: they flood the GnRH receptors continuously, causing them to desensitise and stop responding, which eventually shuts down LH/FSH and testosterone production almost entirely.

Why use both estrogen and an anti-androgen?

Estrogen alone can suppress testosterone, but often not reliably to female range — particularly with oral pills. Combining estrogen with an anti-androgen provides more consistent suppression and allows lower estrogen doses, reducing some risks. Most prescribing guidelines recommend using both until testosterone is stably suppressed, at which point some people transition to estrogen monotherapy (typically via injections or high-dose transdermal).

Progesterone

Progesterone is another naturally occurring female hormone. It is not strictly necessary for trans feminine HRT, but some trans women choose to add it for:

• Breast maturation — possible help with Tanner stage 4/5 development (evidence is largely anecdotal; robust clinical trials are lacking)
• Libido — may increase sexual desire in some individuals
• Mood and sleep — some report a calming effect; others experience the opposite

The recommended form is micronised progesterone (Utrogestan/Prometrium) taken orally or rectally at 100–200 mg/day. Synthetic progestins (e.g. medroxyprogesterone acetate) are generally not recommended as they have a less favourable side effect profile.

Progesterone side effects

Progesterone can cause mood swings, depression, fatigue, or weight gain in some individuals. If adding it, start at a lower dose and monitor how you respond before increasing.

When to add progesterone

Most clinicians who prescribe progesterone recommend waiting until at least 6–12 months into estrogen therapy, to allow baseline breast development to establish first.

Hormone Level Targets

Hormone	Target Range	Purpose
Estradiol (E2)	100–200 pg/mL	Feminisation, bone health, T suppression
Testosterone (T)	< 50 ng/dL	Suppress masculine traits
Progesterone	Not routinely measured	Dose guided by symptoms and response

These are guidelines, not hard rules

Not everyone will achieve both E2 and T targets simultaneously — see the "Key Hormone Targets & Monitoring" section of the main guide for more detail on this.

How Estrogen and Anti-Androgens Work Together

The two mechanisms complement each other and can be thought of in two streams:

Estrogen's indirect T suppression (via HPG axis): Exogenous estradiol → raises blood E2 → hypothalamus and pituitary detect high E2 → LH and FSH output drops → testes receive less LH signal → testosterone production falls

Anti-androgen action (receptor blockade or direct suppression): Bicalutamide/spironolactone → competes with T at androgen receptors → T cannot activate target cells, even if still present CPA/GnRH agonists → suppress LH/FSH directly → testes produce less T upstream

Using both is generally more effective and reliable than either alone, particularly earlier in transition before hormone levels are fully stable.

Summary

Hormone	Role in Trans Feminine HRT	How We Modify It
Estradiol	Primary feminising hormone	Added via pills, patches, gel, or injections
Testosterone	Masculinising hormone to suppress	Reduced with estrogen + anti-androgens
Progesterone	Optional; possible breast maturation and mood benefits	Added after 6–12 months as micronised progesterone
SHBG	Binds and inactivates free sex hormones	Rises naturally with estradiol; not directly targeted
LH / FSH	Signals testes to produce T	Suppressed by estradiol and CPA/GnRH agonists