Therapeutic Applications of Progestogens: A Comprehensive Overview

Progestogens, also known as gestagens, are used in various medical applications for women. They treat menstrual and uterine disorders, aid in fertility and pregnancy support, and manage androgen-dependent skin and hair conditions. Progestogens also play a role in hormone therapy for menopause and hypogonadism, puberty suppression, and appetite stimulation in cachexia. Specific types, like megestrol acetate, are effective for advanced breast cancer and prostate cancer treatment. Additionally, they manage androgen excess in conditions like polycystic ovary syndrome. Progestogens' diverse functions stem from their ability to mimic natural progesterone, offering therapeutic benefits across numerous health issues.

1. Gestogen - structure and functions BY – PIYUSH KUMAR PANDEY

2. Gestogen Referred to as progestogen, gestagen , or gestogen . A medication producing effects similar to the natural female sex hormone progesterone. Available in various formulations and routes of administration. Examples include natural progesterone and progestins like medroxyprogesterone acetate and norethisterone.

3. Medical uses Available Forms: Progestogens come in various forms for diverse administration routes. Forms include oral tablets and capsules, oil and aqueous solutions, suspensions for intramuscular or subcutaneous injection. Other forms: transdermal patches, vaginal rings, intrauterine devices, subcutaneous implants. Birth Control: Progestogens are used in various hormonal birth control methods for women. Combined estrogen and progestogen forms: combined oral contraceptive pills, patches, vaginal rings, and injectables. Progestogen-only forms: mini-pills, emergency contraceptive pills, implants, intrauterine devices, vaginal rings, and injectables.

4. Hormone Therapy: Menopause and Hypogonadism: Progestogens are combined with estrogens in menopausal hormone therapy for women. Used with estrogens for hormone therapy in hypogonadism and delayed puberty in girls and women. Primarily prevent endometrial hyperplasia and reduce the risk of endometrial cancer from unopposed estrogen therapy. Other Uses: High doses of certain progestogens (e.g., megestrol acetate, medroxyprogesterone acetate, cyproterone acetate, chlormadinone acetate) reduce hot flashes in men undergoing androgen deprivation therapy, such as for prostate cancer.

5. Gynecological Disorders: Menstrual Disorders: Progestogens treat menstrual disorders like secondary amenorrhea and dysfunctional uterine bleeding. In a normal menstrual cycle, declining progesterone levels trigger menstruation. Progestogens like norethisterone acetate and medroxyprogesterone acetate induce progesterone-associated breakthrough bleeding. The progestogen challenge test or withdrawal test diagnoses amenorrhea, though it's now rarely used due to available estrogen assays. Uterine Disorders: Progestogens prevent and treat uterine disorders such as endometrial hyperplasia, endometriosis, uterine fibroids, and uterine hypoplasia.

6. Breast Disorders: Progestogens treat benign breast disorders, reducing breast pain, cell proliferation, gland size, and nodularity. Commonly used progestogens: topical progesterone, dydrogesterone , promegestone , lynestrenol , medroxyprogesterone acetate, dienogest , medrogestone . Treat breast hypoplasia and lactation insufficiency by inducing lobuloalveolar development necessary for lactation and breastfeeding. Enlarged Prostate: High-dose progestogens treat benign prostatic hyperplasia (BPH). They suppress gonadal testosterone production, reducing circulating testosterone levels, which in turn inhibits prostate gland growth. Hormone-Sensitive Cancers: Endometrial Cancer: Progestogens have been effective in treating endometrial hyperplasia and endometrial cancer since 1959. Approved treatments include high-dose gestonorone caproate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.

7. Breast Cancer: Progestogens like megestrol acetate and medroxyprogesterone acetate are effective at high doses for advanced postmenopausal breast cancer. Extensively evaluated as second-line therapy. Side effects: dyspnea, weight gain, vaginal bleeding, nausea, fluid retention, hypertension, thrombophlebitis, and thromboembolic complications. Megestrol acetate is inferior to aromatase inhibitors and thus used less in sequential therapy. Only FDA-approved progestogen for breast cancer. Mechanism of action may involve antiestrogenic and/or antigonadotropic effects. Prostate Cancer: High-dose progestogens with antiandrogenic properties used in treatment. Includes cyproterone acetate, chlormadinone acetate, and megestrol acetate. Other studied progestogens: medroxyprogesterone acetate, hydroxyprogesterone caproate, and gestonorone caproate have inadequate effectiveness. Suppress gonadal testosterone production, reducing testosterone levels and inhibiting prostate tumor growth.

8. Fertility and Pregnancy: Fertility Medicine: Progestogens used in fertility treatments for women. Progesterone (and sometimes dydrogesterone or hydroxyprogesterone caproate) used for luteal support in in-vitro fertilization protocols. Pregnancy Support: Progestogens like progesterone, hydroxyprogesterone caproate, dydrogesterone , and allylestrenol support pregnancy. Used for recurrent pregnancy loss and prevention of preterm birth in women with a history of spontaneous preterm birth. Puberty Suppression: Progestogens treat precocious puberty in both boys and girls. Used to delay puberty in transgender youth.

9. Skin and Hair Conditions: Progestogens treat androgen-dependent skin and hair conditions in women. Conditions include oily skin, acne, seborrhea, hirsutism, scalp hair loss, and hidradenitis suppurativa. They suppress testosterone levels and, for antiandrogenic progestogens, directly block androgen actions. Androgen Excess: Progestogens treat hyperandrogenism, like in polycystic ovary syndrome and congenital adrenal hyperplasia in women. Examples: cyproterone acetate and chlormadinone acetate.

10. Appetite Stimulation: Certain progestins used at high doses to increase appetite in conditions like cachexia, anorexia, and wasting syndromes. Typically used in combination with other steroid medications such as dexamethasone. Effects take several weeks to appear but are long-lasting compared to corticosteroids. Recognized as the only medications to increase lean body mass. Lead drug: megestrol acetate for cachexia management, with medroxyprogesterone acetate also used. Mechanism of action for appetite-related effects unknown, possibly unrelated to progestogenic activity. Other progestogens like cyproterone acetate have minimal or no influence on appetite and weight.

11. SIDE EFFECTS Mood Changes Sexual Function Blood clots Cardiovascular health Breast cancer

12. Overdose Progestogens are relatively safe in acute  overdose . Interactions Inhibitors  and  inducers  of  cytochrome P450   enzymes  and other enzymes such as  5α-reductase  may  interact  with progestogens.