Is progesterone (a steroid hormone) ever prescribed alone?

Progesterone Monotherapy: Clinical Indications

Progesterone is rarely prescribed alone in postmenopausal women, with the primary exception being women who have undergone hysterectomy and have residual intra-peritoneal endometriosis; otherwise, progesterone monotherapy lacks therapeutic benefit and is not recommended for hormone replacement. 1

When Progesterone Alone is NOT Appropriate

Postmenopausal Women with Intact Uterus

• Progesterone alone provides no therapeutic advantage for menopausal symptom management or chronic disease prevention 1
• Women with a uterus require estrogen for symptom relief (vasomotor symptoms, urogenital atrophy), with progesterone added solely for endometrial protection 1
• The primary role of progestogen in hormone therapy is endometrial protection against unopposed estrogen, not as standalone therapy 2

Postmenopausal Women After Hysterectomy

• Estrogen-only therapy is the standard approach for women who have had a hysterectomy 1
• There is no therapeutic advantage in prescribing progestins to hysterectomized women, as there is no endometrium requiring protection 1
• The USPSTF found that estrogen alone (without progestogen) in hysterectomized women reduces fractures and breast cancer risk, though it increases stroke and thromboembolic events 1

The Single Exception: Residual Endometriosis

The only clinical scenario where progesterone alone may be prescribed to postmenopausal women is in hysterectomized patients with residual intra-peritoneal endometriosis 1. In this specific situation:

• Progesterone may help manage endometriosis-related symptoms
• This represents a therapeutic indication distinct from hormone replacement therapy
• The progesterone targets the ectopic endometrial tissue rather than serving as hormone replacement

Progesterone in Premenopausal Conditions

Preterm Birth Prevention

• Progesterone monotherapy is used in specific obstetric populations 1
• 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly is recommended for singleton gestations with prior spontaneous preterm birth 1
• Vaginal progesterone (90-mg gel or 200-mg suppository) is offered for women with short cervical length ≤20 mm at ≤24 weeks 1

Secondary Amenorrhea

• Progesterone capsules may be given as monotherapy at 400 mg daily at bedtime for 10 days to induce withdrawal bleeding 3
• This diagnostic/therapeutic use differs from chronic hormone replacement

Endometrial Protection in Specific Populations

• In disease not suited for primary surgery (endometrial cancer), progestational agents like medroxyprogesterone acetate or megestrol acetate may be considered as sole treatment 1
• Patients receiving hormonal therapy alone should be closely monitored with endometrial biopsies every 3-6 months 1

Critical Clinical Pitfall

The most common error is prescribing progesterone alone to postmenopausal women expecting therapeutic benefit for menopausal symptoms. Progesterone monotherapy will not address hot flashes, mood changes, vaginal dryness, or bone loss—these require estrogen therapy 1. The role of progesterone in postmenopausal hormone therapy is exclusively to prevent endometrial hyperplasia and cancer when estrogen is prescribed to women with an intact uterus 4, 2.