Contraception and menopause hormones compared

Contraception: combined methods suppress the gonadotropins. The progestogen slows GnRH pulses, so FSH and LH fall, no follicle develops and no LH surge occurs; it also makes cervical mucus unfriendly to sperm, while the estrogen controls bleeding. Most progestins used alone also suppress ovulation, but the norethindrone pill does so in only about half of users and also thickens mucus. How the levonorgestrel IUS works locally has not been conclusively demonstrated.

Emergency contraception acts before ovulation. Levonorgestrel blunts the LH surge and inhibits follicular rupture, so it works best before ovulation; it will not work if she is already pregnant. Ulipristal, a selective progesterone receptor modulator, still postpones follicular rupture once LH has started to rise, though not on the day of the LH peak, and it is not indicated to terminate an existing pregnancy. Mifepristone is a competitive antagonist at the progesterone receptor; it is labeled, in a regimen with misoprostol, for the medical termination of intrauterine pregnancy through 70 days gestation.

Menopause: estrogens reduce the elevated postmenopausal gonadotropins and are thought to act on hot flashes through the hypothalamic neurokinin B pathway. Fezolinetant blocks that pathway directly: it is a neurokinin 3 receptor antagonist in the thermoregulatory center.

Elevated estrogen increases the synthesis of coagulation factors, and oral estrogen’s hepatic metabolism adds activated protein C resistance; transdermal estrogen bypasses that hepatic step and has minimal impact on VTE risk. Combined pills raise VTE risk most in the first year and when restarting after a break of 4 weeks or longer, though pregnancy raises it as much or more, and the vaginal ring’s VTE risk is similar to that of pills. Epidemiological studies have not linked progestin-only preparations to MI, stroke or VTE.

For combined methods, category 4 of the CDC’s medical eligibility criteria — basically a contraindication — covers smokers aged 35 or older who smoke 15 or more cigarettes a day, migraine with aura, and the first 21 days postpartum. In menopause therapy, the WHI found more stroke and DVT with estrogen alone, and more stroke, DVT, PE and MI with estrogen plus progestin. A woman with a uterus needs a progestogen because unopposed estrogen raises endometrial cancer risk; after hysterectomy it is unnecessary.