2. Hormonal Mechanisms – How Progestins Disrupt the Endocrine System
Step in HPG Axis What Happens with High‑dose/Long‑acting Progestins
Hypothalamus ↑Progestin → ↓GnRH pulse generator activity. Some synthetic progestins have a strong negative feedback effect, reducing GnRH frequency and amplitude.
Pituitary ↓GnRH → ↓LH & FSH secretion. LH surge is blunted or absent; FSH levels fall as well (though FSH may remain slightly elevated in some contexts due to partial agonist properties of certain progestins).
Ovary Low LH → insufficient stimulation of the dominant follicle → no ovulation. The follicles that had begun developing earlier may continue to grow until they atresia or until estrogen production signals a new cycle, but without ovulation they are nonfunctional in terms of fertility.
Endometrium Progesterone from corpus luteum is absent (no corpus luteum formed). Estrogen continues from follicular phase; the endometrium remains proliferative and may become thick or irregular if the cycle is prolonged. If the cycle ends with a withdrawal bleed, the endometrium is shed but without progesterone support, the shedding may be heavier or more frequent.
Clinical implications
The patient can still conceive if she becomes pregnant in a subsequent menstrual cycle (e.g., after taking an ovulation predictor, timed intercourse, or using fertility treatments).
She will not be able to conceive during the cycle that was luteal phase deficient.
If her bleeding pattern is irregular or heavy, she may need evaluation for other causes (e.g., hormonal imbalance, polycystic ovarian syndrome, thyroid dysfunction) and possibly hormone therapy (estrogen/progesterone) to regulate cycles.
Take‑away
During a cycle with an insufficient luteal phase, conception is unlikely because the endometrium is not optimally prepared. However, in future cycles when ovulation and subsequent progesterone secretion are normal, she can conceive normally. If she desires pregnancy soon, she might consider assisted reproductive technologies or hormonal support to ensure adequate luteal function. If she wants to avoid pregnancy, contraception remains necessary regardless of luteal phase status.
