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Determining Menopause in Women Using Depo-Provera
Abstract & Commentary
Beksinska and colleagues from South Africa measured FSH levels in long-term older users of depot-medroxyprogesterone acetate (117 women) and norethindrone enanthate (60 women), long-acting progestin-only methods of contraception. A significant number of these women had postmenopausal levels of FSH (greater than 25 IU/L) at recruitment. The progestin users were compared to 161 nonusers of contraception matched for age. The FSH levels in the groups of women were similar when matched for age. The study did find some suppression of FSH in the first month after injection of the progestin (Beksinska ME, et al. Contraception. 2003;68:339-343).
COMMENT BY LEON SPEROFF, MD
I have written for a long time that menopause can be diagnosed in users of progestin-only contraceptive methods by measuring the FSH level beginning at age 50. This recommendation has been based upon the observation that progestins do not suppress FSH secretion in the normal menstrual cycle. Although old studies had indicated that intramuscular progestin contraception suppressed elevated postmenopausal FSH levels, there was great variability and a lack of total suppression. The important point is that when FSH levels are above the menopausal threshold (20 IU/L), pharmacologic progestin suppression will not restore FSH to a premenopausal level. Therefore, a random FSH measurement can indeed be used to document the onset of postmenopause in users of progestin-only methods of contraception. The South African study indicates that greater reliability is achieved if the blood sample is obtained in the 1 month prior to the next injection (it would be most convenient to draw the blood at the time of the next injection).
A common clinical dilemma is when to change from oral contraception to postmenopausal hormone therapy. It is important to change because even with the lowest estrogen dose oral contraceptive available, the estrogen dose is 4-fold greater than the standard postmenopausal dose, and with increasing age, the dose-related risks with estrogen become significant. My approach is the same as with progestin-only contraception, to establish the onset of the postmenopausal years by measuring the FSH level, beginning at age 50, on an annual basis, being careful to obtain the blood sample on day 6 or 7 of the pill-free week (when steroid levels have declined sufficiently to allow FSH to rise). Friday afternoon works well for patients who start new packages on Sunday. When FSH is > 20 IU/L, it is time to change to a postmenopausal hormone program. I know that many have argued that this approach is not valid because of the variability in FSH levels experienced by women around menopause.1,2 Indeed, in some women, FSH will not rise until 2 weeks after the last pill. Waiting 2 weeks is not very practical and places the patient at risk for an unwanted pregnancy. The pill-free week method is practical and works for most women. Some clinicians are comfortable allowing patients to enter their mid-50s on low-dose oral contraception, then empirically switching to a postmenopausal hormone regimen (The oldest spontaneous pregnancy in the Guinness Book of World Records was 57 years, 120 days). If a patient requires the oral contraceptive for contraception, it is better to follow the empiric route, avoiding an unwanted surprise.
1. Castracance VD, et al. Contraception. 1995;52:371-376.
2. Creinin MD. Fertil Steril. 1996;66:101-104.