Other sex hormones and modulators of the genital system

What is this substance?

Other sex hormones and modulators of the genital system is a therapeutic category that groups together medicines which influence the action of sex hormones such as oestrogen, progesterone, and testosterone. The category appears in NHS formulary chapters under section 6.4, where it is divided into female sex hormones and their modulators, male sex hormones and antagonists, and anabolic steroids.^[3] Medicines in this group include hormone replacement therapy (HRT) products such as Evorel Conti and Premique, progestogens such as medroxyprogesterone acetate and norethisterone, and selective oestrogen receptor modulators such as raloxifene.^[5][2]

Imetelstat is a separate investigational substance that appears in the clinical trial data. It is not itself a sex hormone or a modulator of the genital system, but it is listed here because the trial record is associated with this therapeutic area. Imetelstat is being studied for myelofibrosis, a condition of the bone marrow.^[1]

How does it work?

The formulary sources describe how individual medicines in this category act. Oestrogens used in HRT replace oestrogen that the body no longer produces after menopause, which helps relieve symptoms such as hot flushes and vaginal dryness.^[5] Progestogens such as medroxyprogesterone acetate and norethisterone act on the lining of the womb; norethisterone is used for postponement of menstruation and for heavy menstrual bleeding.^[2] Raloxifene is a selective oestrogen receptor modulator, meaning it activates oestrogen receptors in some tissues and blocks them in others; it is used for preventing osteoporotic fragility fractures in postmenopausal women.^[5]

Dienogest is a progestogen used specifically for endometriosis. It works by reducing the growth of tissue similar to the lining of the womb that grows outside the womb in this condition.^[4] Testosterone products used in men with hypogonadism replace testosterone when the body does not produce enough of it.^[3] Fezolinetant, listed in the Norfolk and Waveney formulary, works differently: it blocks neurokinin 3 receptors and is used for moderate to severe vasomotor symptoms associated with menopause.^[4]

The mechanism of action of imetelstat is not described in the provided trial record. The trial summary states only that it is being compared with best available therapy for overall survival in myelofibrosis.^[1]

Which conditions is it used or studied for?

• Menopause symptoms — oestrogen-containing HRT products are used for oestrogen deficiency symptoms in postmenopausal women.^[5][2]
• Vasomotor symptoms of menopause — fezolinetant is used for moderate to severe hot flushes and night sweats associated with menopause.^[4]
• Endometriosis — dienogest is listed as a treatment for endometriosis in two NHS formularies.^[4][2]
• Heavy menstrual bleeding — progestogens such as norethisterone and medroxyprogesterone acetate are used for this indication.^[2]
• Osteoporosis prevention — raloxifene is used for the primary prevention of osteoporotic fragility fractures in postmenopausal women.^[5]
• Male hypogonadism — testosterone gel and injection products are used for testosterone replacement therapy in men with confirmed testosterone deficiency.^[3]
• Myelofibrosis — imetelstat is being studied in a Phase 3 trial for intermediate-2 or high-risk myelofibrosis that is relapsed or refractory to JAK-inhibitor treatment.^[1]

How is it given?

The medicines in this category are given in many different forms. Oestrogen-containing HRT products are available as patches, tablets, gels, and transdermal sprays.^[5][2] Progestogens are given as tablets, pessaries, and injections; medroxyprogesterone acetate is available as an injectable product under the brand name Depo-Provera.^[5] Raloxifene is given as a 60 mg tablet.^[2] Testosterone is available as a gel, a cream, and an injectable product.^[4][3]

Imetelstat is given intravenously. The trial record lists a dose of 9.4 mg per kilogram of body weight.^[1]

What do the clinical trials show?

The clinical trial data contains one study of imetelstat, a Phase 3 randomised trial in myelofibrosis.^[1] The trial is authorised but not yet recruiting. It plans to enroll 354 participants with intermediate-2 or high-risk myelofibrosis whose disease is relapsed or refractory to JAK-inhibitor treatment.^[1]

The primary outcome is overall survival, defined as the time from randomisation to death from any cause.^[1] Participants are randomised to receive either imetelstat or best available therapy. The trial is interventional in design.^[1]

No results are yet available because the trial has not started recruiting. The registry record provides the study design and planned enrollment but no efficacy or safety findings.^[1]

What side effects are known?

The formulary sources report side effects for some medicines in this category. The Norfolk and Waveney formulary notes that fezolinetant carries a risk of liver injury. The MHRA recommends liver function tests before treatment, monthly during the first three months, and periodically thereafter. Patients should seek immediate medical attention if they develop signs of liver injury including fatigue, itching, jaundice, dark urine, pale stools, nausea, vomiting, decreased appetite, or abdominal pain.^[4]

Finasteride, a male sex hormone antagonist, carries a reminder from the MHRA about the risk of psychiatric side effects and sexual side effects, which may persist after stopping treatment.^[3] Topical testosterone gel carries a risk of harm to children following accidental exposure.^[3] No side effect information for imetelstat is provided in the trial record.^[1]