Sex hormones

Overview and Clinical Classification
Sex hormones are a pharmacological group of endogenous and synthetic steroid hormones responsible for the development and regulation of reproductive systems, secondary sexual characteristics, and a wide array of metabolic and physiological processes. They are broadly classified into estrogens, progestogens (progestins), and androgens, with each group having specific indications in medical practice, including contraception, hormone replacement therapy (HRT), treatment of endocrine disorders, and adjunctive cancer therapy.

This class also includes synthetic analogs and combination formulations. Their pharmacological effect can be agonistic, antagonistic, or modulatory, depending on the receptor interaction and clinical indication.

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Categories of Sex Hormones

1. Estrogens

Estrogens are primarily involved in female reproductive health, promoting the development of the uterus, breast, and secondary sexual characteristics.

• Natural and Synthetic Estrogens

  • Estradiol (E2) – endogenous primary estrogen

  • Estrone (E1)

  • Estriol (E3)

  • Ethinylestradiol (EE) – synthetic, used in contraceptives

  • Conjugated estrogens (Premarin)

  • Estetrol (E4) – newer estrogen with selective activity

• Therapeutic Uses

  • Hormone replacement therapy (HRT) in menopause

  • Contraception (combined oral contraceptives)

  • Hypogonadism in females

  • Prevention of osteoporosis

  • Certain types of breast and prostate cancers (palliative)

• Formulations

  • Oral tablets, transdermal patches, gels, vaginal creams, rings, injectables

2. Progestogens (Progestins)

Progestogens maintain the uterine lining for pregnancy and counterbalance estrogen’s proliferative effects.

• Natural Progestogen

  • Progesterone

• Synthetic Progestins

  • Medroxyprogesterone acetate (MPA)

  • Norethisterone (norethindrone)

  • Levonorgestrel

  • Desogestrel

  • Drospirenone

  • Dydrogesterone

• Uses

  • Contraception (progestin-only or combined)

  • Menstrual disorders (dysmenorrhea, amenorrhea)

  • Endometriosis

  • Threatened or recurrent miscarriage

  • Hormone therapy adjunct in estrogen-containing HRT to prevent endometrial hyperplasia

• Formulations

  • Oral, depot injections, intrauterine devices (IUDs), implants, vaginal gels

3. Androgens

Androgens are responsible for male sexual development, muscle mass, bone density, and libido.

• Endogenous Androgens

  • Testosterone

  • Dihydrotestosterone (DHT)

  • Androstenedione

• Synthetic Androgens/Anabolic Steroids

  • Methyltestosterone

  • Testosterone enanthate, cypionate, undecanoate

  • Nandrolone

• Uses

  • Male hypogonadism

  • Delayed puberty in boys

  • Postmenopausal HRT (off-label, for libido)

  • Anemia of chronic disease (as adjunct)

  • Cachexia (e.g., in cancer or AIDS)

• Formulations

  • Transdermal gels, intramuscular injections, oral capsules, subcutaneous pellets

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Mechanism of Action

Sex hormones exert effects by binding to nuclear hormone receptors:

• Estrogens bind to ERα and ERβ receptors

• Progestogens bind to progesterone receptors (PR-A and PR-B)

• Androgens bind to androgen receptors (AR)

This binding alters gene transcription and protein synthesis, affecting cell growth, differentiation, reproductive cycle, and metabolism.

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Clinical Indications by Sex Hormone Type

Hormone Class	Common Indications
Estrogens	Menopausal symptoms, hypogonadism, contraception, osteoporosis
Progestins	Contraception, endometriosis, menstrual disorders, adjunct HRT
Androgens	Hypogonadism, delayed puberty, HRT, anabolic purposes

Combination Products

Combination Type	Brand Examples
Estrogen + Progestin (COC)	Microgynon, Yasmin, Diane-35
Estrogen + Progestin (HRT)	Femoston, Activelle, Premique
Progestin-only contraceptives	Cerazette (Desogestrel), Depo-Provera
Estrogen + Androgen (rare, off-label)	Estratest (Estradiol + Methyltestosterone)

Adverse Effects

Hormone Type	Common Side Effects	Serious Risks
Estrogens	Nausea, breast tenderness, headache	Thrombosis, stroke, breast/endometrial cancer
Progestins	Weight gain, mood changes, bloating	Depression, androgenic effects, breast cancer
Androgens	Acne, voice deepening, hair growth, fluid retention	Hepatic toxicity, cardiovascular events

Contraindications

Hormone Type	Key Contraindications
Estrogens	Breast cancer, estrogen-dependent neoplasia, thromboembolism
Progestins	Liver dysfunction, unexplained vaginal bleeding
Androgens	Prostate/breast cancer in men, polycythemia, severe heart failure

Drug Interactions

Interaction	Affected Hormones	Clinical Effect
Rifampin, carbamazepine	All steroid hormones	↓ efficacy due to CYP3A4 induction
Warfarin	Estrogens, Androgens	Estrogens ↑ clotting → ↓ warfarin effect
Insulin/antidiabetics	Estrogens	Antagonize glycemic control
Corticosteroids	Androgens	Additive effect on fluid retention

Monitoring Parameters

• Estrogens: BP, lipid profile, mammogram, endometrial thickness

• Progestins: Mood, weight, bleeding patterns

• Androgens: Testosterone levels, liver enzymes, PSA (men), lipid profile

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Use in Special Populations

Population	Considerations
Pregnancy	Estrogens and androgens contraindicated
Breastfeeding	Progestin-only contraception preferred
Elderly	HRT risks vs benefits must be individually assessed
Children	Use restricted to specific endocrine indications (e.g., delayed puberty)

Regulatory and Safety Notes

• Black Box Warnings:

  • Estrogen products (e.g., conjugated estrogens) carry warnings for cardiovascular disease, stroke, breast cancer, and dementia.

  • Testosterone products carry risks of cardiovascular events, misuse/abuse (especially among athletes).

• Hormonal therapy in transgender individuals involves complex use of estrogens, progestins, and antiandrogens, managed by specialists.

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Hormone Modulators (Related Agents)

These are not hormones per se but modulate hormone receptors:

• Selective Estrogen Receptor Modulators (SERMs): Tamoxifen, Raloxifene

• Aromatase Inhibitors: Anastrozole, Letrozole (reduce estrogen synthesis)

• Anti-androgens: Flutamide, Bicalutamide (block AR in prostate cancer)

• GnRH Agonists/Antagonists: Leuprolide, Goserelin – suppress gonadotropin release

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Examples of Brand and Generic Products

Product	Components
Yasmin	Drospirenone + Ethinylestradiol
Premarin	Conjugated equine estrogens
Evorel Conti	Estradiol + Norethisterone (patch)
Nebido	Testosterone undecanoate (IM injection)
Depo-Provera	Medroxyprogesterone acetate (depot injection)
Femoston	Estradiol + Dydrogesterone

Therapeutic Guidelines

• Menopause: HRT should be used at lowest effective dose for shortest duration.

• Contraception: Selection based on age, thrombotic risk, comorbidities.

• Male hypogonadism: Testosterone therapy reserved for confirmed low levels and symptoms.

• Cancer: Tamoxifen or aromatase inhibitors often replace estrogens.